Placebo Effects and Informed Consent.

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Alfano, Mark

2015-01-01

The concepts of placebos and placebo effects refer to extremely diverse phenomena. I recommend dissolving the concepts of placebos and placebo effects into loosely related groups of specific mechanisms, including (potentially among others) expectation-fulfillment, classical conditioning, and attentional-somatic feedback loops. If this approach is on the right track, it has three main implications for the ethics of informed consent. First, because of the expectation-fulfillment mechanism, the process of informing cannot be considered independently from the potential effects of treatment. Obtaining informed consent influences the effects of treatment. This provides support for the authorized concealment and authorized deception paradigms, and perhaps even for outright deceptive placebo use. Second, doctors may easily fail to consider the potential benefits of conditioning, leading them to misjudge the trade-off between beneficence and autonomy. Third, how attentional-somatic feedback loops play out depends not only on the content of the informing process but also on its framing. This suggests a role for libertarian paternalism in clinical practice.

Placebo analgesia: understanding the mechanisms

OpenAIRE

Medoff, Zev M; Colloca, Luana

2015-01-01

Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo a...

PLACEBO EFFECTS IN COMPETITIVE SPORT: QUALITATIVE DATA

Directory of Open Access Journals (Sweden)

Christopher J. Beedie

2007-03-01

Full Text Available The paper examines the placebo effect in sports performance. The possibility that the placebo effect is a more common phenomenon than the quantity of published research would suggest is briefly addressed. It is suggested that the placebo control design often used in sports performance research masks any placebo effects and thus presents a false picture of the mechanisms underlying performance-enhancing interventions in the real world. An electronic survey was sent to 48 competitive, international and professional athletes. Questions related to the placebo effect in competitive sport. Thirty responses were received. Data indicate that the majority (97% of respondents believe that the placebo effect can exert an influence on sports performance, and that a significant number (73% have experienced what they defined as a placebo effect. Inductive content analysis reveals that these experiences fall into several categories such as explicit placebo effects, inadvertent false beliefs, ritual and reverse placebo effects. Furthermore, 10 respondents (33% offer explanations as to the nature of the placebo effect. Again, inductive content analysis reveals that these explanations fall into several categories including deliberate changes in competitive strategy, belief/expectancy, faith in a third party, and marketing. Overall, responses support previous experimental research and anecdotal reports that have found a relationship between belief and sports performance. It is suggested that further research be structured to not simply control for the placebo effect, but to elucidate it

The early history of the placebo.

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Jütte, Robert

2013-04-01

In the late 18th century the term "placebo" became part of medical jargon. In contrast to the prevailing opinion that it was the Scottish physician and pharmacologist William Cullen (1710-1790) who introduced this expression into medical language in 1772, the credit must be given to another English physician, Alexander Sutherland (born before 1730 - died after 1773). The main reason for administering placebos in late 18th-century medical practice was to satisfy the patient's demand and his expectations. Another reason was obstinancy of the patient: the motivation behind such prescriptions may be summarized as prescribing inert drugs for the satisfaction of the patient's mind, and not with the view of producing any direct remedial effect. In most cases these 18th century physicians did not administer "pure" placebos but resorted to any kind of medicine which they thought simple, feeble, or altogether powerless, non-perturbing medicines. Today we make the distinction between pure placebos (substances with no pharmacological effect, e.g. sugar pills) and impure placebos (substances with pharmacological effect but not on the condition being treated). In the 18th century those physicians who prescribed placebo usually thought of drugs which were considered not very effective in the particular case, e.g. a mild ointment. At the same time, only very few brilliant minds came up with the ingenious idea of using inert substances as placebo. An alternative to milk sugar used as placebo in homeopathy was breadpills. Recent research suggests that expectancy is an integral part of the placebo effect. As early as 1775 the English bishop John Douglas (1721-1807) anticipated the findings of modern research on the placebo effect. Copyright © 2012 Elsevier Ltd. All rights reserved.

How placebos change the patient's brain.

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Benedetti, Fabrizio; Carlino, Elisa; Pollo, Antonella

2011-01-01

Although placebos have long been considered a nuisance in clinical research, today they represent an active and productive field of research and, because of the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. Indeed, there exists not a single but many placebo effects, with different mechanisms and in different systems, medical conditions, and therapeutic interventions. For example, brain mechanisms of expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena, such as Pavlovian conditioning, cognitive, and social learning. There is also some experimental evidence of different genetic variants in placebo responsiveness. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, the neural networks that are involved have been identified: that is, the opioidergic-cholecystokinergic-dopaminergic modulatory network in pain and part of the basal ganglia circuitry in Parkinson's disease. Important clinical implications emerge from these recent advances in placebo research. First, as the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and rituals of the therapeutic act, may change the chemistry and circuitry of the patient's brain. Second, the mechanisms that are activated by placebos are the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Third, if prefrontal functioning is impaired, placebo responses are reduced or totally lacking, as occurs in dementia of the Alzheimer's type.

Semiotics and the placebo effect.

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Miller, Franklin G; Colloca, Luana

2010-01-01

Despite substantial progress in elucidating its neurobiological mechanisms, theoretical understanding of the placebo effect is poorly developed. Application of the semiotic theory developed by the American philosopher Charles Peirce offers a promising account of placebo effects as involving the apprehension and response to signs. The semiotic approach dovetails with the various psychological mechanisms invoked to account for placebo effects, such as conditioning and expectation, and bridges the biological and cultural dimensions of this fascinating phenomenon.

Neurobiological mechanisms of placebo responses.

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Zubieta, Jon-Kar; Stohler, Christian S

2009-03-01

Expectations, positive or negative, are modulating factors influencing behavior. They are also thought to underlie placebo effects, potentially impacting perceptions and biological processes. We used sustained pain as a model to determine the neural mechanisms underlying placebo-induced analgesia and affective changes in healthy humans. Subjects were informed that they could receive either an active agent or an inactive compound, similar to routine clinical trials. Using PET and the mu-opioid selective radiotracer [(11)C]carfentanil we demonstrate placebo-induced activation of opioid neurotransmission in a number of brain regions. These include the rostral anterior cingulate, orbitofrontal and dorsolateral prefrontal cortex, anterior and posterior insula, nucleus accumbens, amygdala, thalamus, hypothalamus, and periaqueductal grey. Some of these regions overlap with those involved in pain and affective regulation but also motivated behavior. The activation of endogenous opioid neurotransmission was further associated with reductions in pain report and negative affective state. Additional studies with the radiotracer [(11)C]raclopride, studies labeling dopamine D2/3 receptors, also demonstrate the activation of nucleus accumbens dopamine during placebo administration under expectation of analgesia. Both dopamine and opioid neurotransmission were related to expectations of analgesia and deviations from those initial expectations. When the activity of the nucleus accumbens was probed with fMRI using a monetary reward expectation paradigm, its activation was correlated with both dopamine, opioid responses to placebo in this region and the formation of placebo analgesia. These data confirm that specific neural circuits and neurotransmitter systems respond to the expectation of benefit during placebo administration, inducing measurable physiological changes.

Acupuncture, psyche and the placebo response.

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Enck, Paul; Klosterhalfen, Sibylle; Zipfel, Stephan

2010-10-28

With growing use of acupuncture treatment in various clinical conditions, the question has been posed whether the reported effects reflect specific mechanisms of acupuncture or whether they represent placebo responses, as they often are similar in effect size and resemble similarities to placebo analgesia and its mechanisms. We reviewed the available literature for different placebos (sham procedures) used to control the acupuncture effects, for moderators and potential biases in respective clinical trials, and for central and peripheral mechanisms involved that would allow differentiation of placebo effects from acupuncture and sham acupuncture effects. While the evidence is still limited, it seems that biological differences exist between a placebo response, e.g. in placebo analgesia, and analgesic response during acupunture that does not occur with sham acupuncture. It seems advisable that clinical trials should include potential biomarkers of acupuncture, e.g. measures of the autonomic nervous system function to verify that acupuncture and sham acupuncture are different despite similar clinical effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Differential effectiveness of placebo treatments

DEFF Research Database (Denmark)

Meissner, Karin; Fässler, Margrit; Rücker, Gerta

2013-01-01

IMPORTANCE When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications...... relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects...... and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ...

Placebo treatment facilitates social trust and approach behavior.

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Yan, Xinyuan; Yong, Xue; Huang, Wenhao; Ma, Yina

2018-05-29

Placebo effect refers to beneficial changes induced by the use of inert treatment, such as placebo-induced relief of physical pain and attenuation of negative affect. To date, we know little about whether placebo treatment could facilitate social functioning, a crucial aspect for well-being of a social species. In the present study, we develop and validate a paradigm to induce placebo effects on social trust and approach behavior (social placebo effect), and show robust evidence that placebo treatment promotes trust in others and increases preference for a closer interpersonal distance. We further examine placebo effects in real-life social interaction and show that placebo treatment makes single, but not pair-bonded, males keep closer to an attractive first-met female and perceive less social anxiety in the female. Finally, we show evidence that the effects of placebo treatment on social trust and approach behavior can be as strong as the effect of intranasal administration of oxytocin, a neuropeptide known for its function in facilitating social cognition and behavior. The finding of the social placebo effect extends our understanding of placebo effects on improvement of physical, mental, and social well-being and suggests clinical potentials in the treatment of social dysfunction.

Importance of placebo effect in cough clinical trials.

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Eccles, Ron

2010-01-01

Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

Placebo Trends across the Border: US versus Canada.

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Harris, Cory S; Campbell, Natasha K J; Raz, Amir

2015-01-01

Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate interpretation and prevent direct comparisons across studies. While US- and Canada-based physicians share similar professional standards, Canada harbours a less-litigious universal healthcare model with no formal placebo-related policy-factors that may impact how physicians view and use placebos. To compare American and Canadian data, we circulated an online survey to academic physicians practicing in Canada, collected anonymous responses, and extracted those of internists and rheumatologists for comparison to US data obtained through parallel methodologies. Whereas our data show overall concordance across the border-from definitions to ethical limitations and therapeutic potential-differences between American- and Canadian-based placebo practices merit acknowledgement. For example, compared to 45%-80% among US-based respondents, only 23±7% of Canada-based respondents reported using placebos in clinical practice. However, 79±7% of Canada-respondents-a figure comparable to US data-professed to prescribing at least one form of treatment without proven or expected efficacy. Placebo interventions including unwarranted vitamins and herbal supplements (impure placebos) as well as sugar pills and saline injections (pure placebos) appear more common in Canada, where more doctors described placebos as "placebos" (rather than "medications") and used them as a "diagnostic" tool (rather than a means of placating patient demands for treatment). Cross-border variation in the use of clinical placebos appears minor despite substantial differences in health care delivery system, malpractice climate, and placebo-related policy. The prevalence of impure placebos in both Canadian and US clinics raises ethical and practical questions currently unaddressed by policy and warranting investigation.

Hypnosis: placebo or nonplacebo?

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Van Dyck, R; Hoogduin, K

1990-07-01

According to Grünbaum's definition of placebo, a therapeutic procedure can be considered a nonplacebo if it can be demonstrated that its effects are produced according to the theory upon which the therapy is based. If the theory is adopted that hypnotic effects depend upon mobilization of the patient's hypnotizability, which is a measurable characteristic, a testable theory is provided. Experimental literature is reviewed that shows that placebo effects are not related to hypnotizability. Clinical outcome studies make it clear that results of hypnotherapy are related to hypnotizability in some disorders such as pain and anxiety, but not in the treatment of addiction or habit disorders. An example of a procedure is given in which hypnosis is nonetheless usefully applied for its placebo value as a method to generate positive expectancies.

Placebo Trends across the Border: US versus Canada

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Harris, Cory S.; Campbell, Natasha K. J.; Raz, Amir

2015-01-01

Background Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate interpretation and prevent direct comparisons across studies. While US- and Canada-based physicians share similar professional standards, Canada harbours a less-litigious universal healthcare model with no formal placebo-related policy—factors that may impact how physicians view and use placebos. Methods To compare American and Canadian data, we circulated an online survey to academic physicians practicing in Canada, collected anonymous responses, and extracted those of internists and rheumatologists for comparison to US data obtained through parallel methodologies. Results Whereas our data show overall concordance across the border—from definitions to ethical limitations and therapeutic potential—differences between American- and Canadian-based placebo practices merit acknowledgement. For example, compared to 45%-80% among US-based respondents, only 23±7% of Canada-based respondents reported using placebos in clinical practice. However, 79±7% of Canada-respondents—a figure comparable to US data—professed to prescribing at least one form of treatment without proven or expected efficacy. Placebo interventions including unwarranted vitamins and herbal supplements (impure placebos) as well as sugar pills and saline injections (pure placebos) appear more common in Canada, where more doctors described placebos as “placebos” (rather than “medications”) and used them as a “diagnostic” tool (rather than a means of placating patient demands for treatment). Interpretation Cross-border variation in the use of clinical placebos appears minor despite substantial differences in health care delivery system, malpractice climate, and placebo-related policy. The prevalence of impure placebos in both Canadian and US clinics raises ethical and practical questions currently unaddressed

Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos.

Directory of Open Access Journals (Sweden)

Felicity L Bishop

Full Text Available Placebo groups are used in randomised clinical trials (RCTs to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.We conducted a content analysis of 45 Participant Information Leaflets (PILs using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database. Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%, but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001 and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001 or adverse effects (4 vs. 39, p<001. 8 PILs (18% explicitly stated that the placebo treatment was either undesirable or ineffective.PILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled

[Placebo and the relationship between doctors and patients. Overview].

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Scriba, P C

2012-09-01

In medicine, placebos are used both in scientific studies and for practical therapeutic purposes. In evidence-based medicine, the efficacy of treatment may be determined as the difference between the effects of the verum (the active study drug) and the placebo, the latter being a substance lacking specific action on the disease under consideration. However, the improvements in patients' conditions under placebo treatment may be substantial and comparable to those with verum. Genuine placebos predominate in clinical studies, while pseudoplacebos prevail in practical therapy. The term pseudoplacebo can also be applied to many procedures in complementary medicine, including homeopathic medicine (Büchel et al., Placebo in der Medizin, 2011). The comprehensive definition of placebo, as used in a report by the German Medical Association (Büchel et al., Placebo in der Medizin, 2011), states that a placebo effect may occur even when treating with verum. The placebo effect is modulated by the context of the treatment, by the expectations of the patients and the doctors, and by the success of the relationship between doctors and patients. A number of unspecific effects, e.g., spontaneous alleviation, statistical effects, variance with time, methodological errors, in addition to the placebo effect make up the total response that is called"placebo reaction." A complete list of the effectiveness of placebo for all important diseases is still lacking. Further, it is not possible to predict which patients will respond to placebo. Which characteristics of doctors are important (competence, empathy, communicative ability and partnership, trust) in order to achieve a placebo effect, particularly in addition to the verum effect measures of evidence-based medicine? Are there doctors who are better in this than others? Could the nocebo effect weaken the efficacy of treatment in evidence-based medicine? Since a placebo effect may occur in almost any standard therapy, information about

Relieving Pain using Dose-Extending Placebos: A Scoping Review

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Colloca, Luana; Enck, Paul; DeGrazia, David

2017-01-01

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated. PMID:27023425

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

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Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J

2015-01-01

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

New insights into the placebo and nocebo responses.

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Enck, Paul; Benedetti, Fabrizio; Schedlowski, Manfred

2008-07-31

In modern medicine, the placebo response or placebo effect has often been regarded as a nuisance in basic research and particularly in clinical research. The latest scientific evidence has demonstrated, however, that the placebo effect and the nocebo effect, the negative effects of placebo, stem from highly active processes in the brain that are mediated by psychological mechanisms such as expectation and conditioning. These processes have been described in some detail for many diseases and treatments, and we now know that they can represent both strength and vulnerability in the course of a disease as well as in the response to a therapy. However, recent research and current knowledge raise several issues that we shall address in this review. We will discuss current neurobiological models like expectation-induced activation of the brain reward circuitry, Pavlovian conditioning, and anxiety mechanisms of the nocebo response. We will further explore the nature of the placebo responses in clinical trials and address major questions for future research such as the relationship between expectations and conditioning in placebo effects, the existence of a consistent brain network for all placebo effects, the role of gender in placebo effects, and the impact of getting drug-like effects without drugs.

The Application of Persuasion Theory to Placebo Effects.

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Geers, Andrew L; Briñol, Pablo; Vogel, Erin A; Aspiras, Olivia; Caplandies, Fawn C; Petty, Richard E

2018-01-01

Placebo effects, or positive outcomes resulting from expectations about a treatment, are powerful components of modern medical care. In this chapter, we suggest that our understanding of placebo effects may benefit from more explicitly connecting this phenomenon to the existing empirical psychological literature on persuasion. Persuasion typically involves an attempt to bring about a change in beliefs or attitudes as a result of providing information on a topic. We begin by providing a brief overview of the psychological literature on placebo effects. We then point to connections between this literature and research on persuasive communication. Although some links have been made, these initial connections have predominantly relied on classic theories of persuasion rather than on more contemporary and comprehensive models. Next, we describe a modern theory of persuasion that may facilitate the study of placebo effects and analyze two issues pertinent to the literature on placebo effects from the lens of this model. Specifically, we consider how and when characteristics of a practitioner (e.g., variables such as perceptions of a practitioner's confidence or competence) can influence the magnitude of placebo effects, and how modern persuasion theory can help in understanding the durability of placebo effects over time. We conclude that examining placebo effects as an outcome of persuasive communication would be a fruitful line of future research. © 2018 Elsevier Inc. All rights reserved.

Harnessing placebo effects by targeting expectancies

NARCIS (Netherlands)

Peerdeman, K.J.

2018-01-01

Placebo effects are health improvements, for example pain reduction, due to an inert treatment. These effects are typically ascribed to a person’s expectations about the beneficial outcomes of the placebo. The literature and experimental research in the current dissertation shows that

Nursing knowledge: hints from the placebo effect.

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Zanotti, Renzo; Chiffi, Daniele

2017-07-01

Nursing knowledge stems from a dynamic interplay between population-based scientific knowledge (the general) and specific clinical cases (the particular). We compared the 'cascade model of knowledge translation', also known as 'classical biomedical model' in clinical practice (in which knowledge gained at population level may be applied directly to a specific clinical context), with an emergentist model of knowledge translation. The structure and dynamics of nursing knowledge are outlined, adopting the distinction between epistemic and non-epistemic values. Then, a (moderately) emergentist approach to nursing knowledge is proposed, based on the assumption of a two-way flow from the general to the particular and vice versa. The case of the 'placebo effect' is analysed as an example of emergentist knowledge. The placebo effect is usually considered difficult to be explained within the classical biomedical model, and we underscore its importance in shaping nursing knowledge. In fact, nurses are primarily responsible for administering placebo in the clinical setting and have an essential role in promoting the placebo effect and reducing the nocebo effect. The beliefs responsible for the placebo effect are as follows: (1) interactive, because they depend on the relationship between patients and health care professionals; (2) situated, because they occur in a given clinical context related to certain rituals; and (3) grounded on higher order beliefs concerning what an individual thinks about the beliefs of others. It is essential to know the clinical context and to understand other people's beliefs to make sense of the placebo effect. The placebo effect only works when the (higher order) beliefs of doctors, nurses and patients interact in a given setting. Finally, we argue for a close relationship between placebo effect and nursing knowledge. © 2016 John Wiley & Sons Ltd.

Motivation and placebos: do different mechanisms occur in different contexts?

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Hyland, Michael E

2011-06-27

This paper challenges the common assumption that the mechanisms underlying short-term placebo paradigms (where there is no motivation for health improvement) and long-term placebo paradigms (where patients value improvement in their health) are the same. Three types of motivational theory are reviewed: (i) classical placebo motivation theory that the placebo response results from the desire for therapeutic improvement; (ii) goal activation model that expectancy-driven placebo responses are enhanced when the placebo response satisfies an activated goal; and (iii) motivational concordance model that the placebo response is the consequence of concordance between the placebo ritual and significant intrinsic motives. It is suggested that current data are consistent with the following theory: response expectancy, conditioning and goal activation are responsible for short-term placebo effects but long-term therapeutic change is achieved through the effects of goal satisfaction and affect on the inflammatory response system and hypothalamic-pituitary-adrenal axis. Empirical predictions of this new theory are outlined, including ways in which placebo effects can be combined with other psychologically mediated effects on short-term and long-term psychological and physiological state.

Utilizing placebo mechanisms for dose reduction in pharmacotherapy.

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Doering, Bettina K; Rief, Winfried

2012-03-01

The knowledge and systematic application of the placebo effect remains limited, although its importance to the treatment of various medical conditions has increasingly been recognized. A possible application of the placebo effect to pharmacotherapy is seen in conditioning processes that aim at a placebo-controlled dose reduction of drugs while maintaining the efficacy of the medical treatment. The pairing of a placebo and a pharmacological agent may achieve satisfactory treatment outcomes in combination with a lower dose of medication. This procedure includes classic and instrumental conditioning processes that involve both conscious and non-conscious information processing. Although recent studies have gathered preliminary evidence for the efficacy of placebo-controlled dose reduction (e.g. in psoriasis and attention deficit hyperactivity disorder [ADHD]), they have also illustrated the difficulties that are inherent to this approach. We critically review previous approaches and discuss designs for clinical trials that seem appropriate to the investigation of conditioned placebo effects in pharmacotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhancing Placebo Effects: Insights From Social Psychology

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SLIWINSKI, JIM; ELKINS, GARY R.

2012-01-01

Placebo effects are widely recognized as having a potent impact upon treatment outcomes in both medical and psychological interventions, including hypnosis. In research utilizing randomized clinical trials, there is usually an effort to minimize or control placebo effects. However, in clinical practice there may be significant benefits in enhancing placebo effects. Prior research from the field of social psychology has identified three factors that may enhance placebo effects, namely: priming, client perceptions, and the theory of planned behavior. These factors are reviewed and illustrated via a case example. The consideration of social-psychological factors to enhance positive expectancies and beliefs has implications for clinical practice as well as future research into hypnotic interventions. PMID:23488251

Placebo-like analgesia via response imagery

NARCIS (Netherlands)

Peerdeman, K.J.; Laarhoven, A.I.M. van; Bartels, D.J.P.; Peters, M.L.; Evers, A.W.M.

2017-01-01

BACKGROUND: Placebo effects on pain are reliably observed in the literature. A core mechanism of these effects is response expectancies. Response expectancies can be formed by instructions, prior experiences and observation of others. Whether mental imagery of a response can also induce placebo-like

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

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Kosek, Eva; Rosen, Annelie; Carville, Serena; Choy, Ernest; Gracely, Richard H; Marcus, Hanke; Petzke, Frank; Ingvar, Martin; Jensen, Karin B

2017-07-01

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Homeopathic pathogenetic trials produce specific symptoms different from placebo.

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Möllinger, Heribert; Schneider, Rainer; Walach, Harald

2009-04-01

Homeopathy uses information gathered from healthy volunteers taking homeopathic substances (pathogenetic trials) for clinical treatment. It is controversial whether such studies produce symptoms different from those produced by placebo. To test whether homeopathic preparations produce different symptoms than placebo in healthy volunteers. Three armed, double-blind, placebo controlled randomised experimental pathogenetic study in 25 healthy volunteers who took either one of two homeopathic remedies, Natrum muriaticum and Arsenicum album in 30CH or identical placebo. Main outcome parameter was the number of remedy-specific symptoms per group. On average, 6 symptoms typical for Arsenicum album were experienced by participants taking arsenicum album, 5 symptoms typical for Natrum muriaticum by those taking natrum muriaticum, and 11 non-specific symptoms by those in the placebo group. Differences were significant overall (Kruskall Wallis test, p = 0.0002,) and significantly different from placebo (Mann-Whitney test, p = 0.001). Homeopathic remedies produce different symptoms than placebo. Copyright (c) 2009 S. Karger AG, Basel.

Mechanisms of the placebo response in pain in osteoarthritis.

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Abhishek, A; Doherty, M

2013-09-01

Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants. A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review. Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs. Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

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Mease, Philip; Hall, Stephen; FitzGerald, Oliver; van der Heijde, Désirée; Merola, Joseph F; Avila-Zapata, Francisco; Cieślak, Dorota; Graham, Daniela; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

2017-10-19

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3. ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; Ptofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; Ptofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious

On Suggestibility and Placebo: A Follow-Up Study.

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Lifshitz, Michael; Sheiner, Eli O; Olson, Jay A; Thériault, Rémi; Raz, Amir

2017-04-01

Identifying what makes some people respond well to placebos remains a major challenge. Here, we attempt to replicate an earlier study in which we found a relationship between hypnotic suggestibility and subjective ratings of relaxation following the ingestion of a placebo sedative (Sheiner, Lifshitz, & Raz, 2016). To assess the reliability of this effect, we tested 34 participants using a similar design. Participants ingested a placebo capsule in one of two conditions: (1) relaxation, wherein we described the capsule as a herbal sedative, or (2) control, wherein we described the capsule as inert. To index placebo response, we collected measures of blood pressure and heart rate, as well as self-report ratings of relaxation and drowsiness. Despite using a similar experimental design as in our earlier study, we were unable to replicate the correlation between hypnotic suggestibility and placebo response. Furthermore, whereas in our former experiment we observed a change in subjective ratings of relaxation but no change in physiological measures, here we found that heart rate dropped in the relaxation condition while subjective ratings remained unchanged. Even within a consistent context of relaxation, therefore, our present results indicate that placebos may induce effects that are fickle, tenuous, and unreliable. Although we had low statistical power, our findings tentatively accord with the notion that placebo response likely involves a complex, multifaceted interaction between traits, expectancies, and contexts.

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

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Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

2002-04-01

To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

Suicide risk in placebo-controlled studies of major depression

NARCIS (Netherlands)

Storosum, J. G.; van Zwieten, B. J.; van den Brink, W.; Gersons, B. P.; Broekmans, A. W.

2001-01-01

The purpose of this study was to determine if fear of an increased risk of attempted suicide in placebo groups participating in placebo-controlled studies is an argument against the performance of placebo-controlled trials in studies of major depression. All short-term and long-term,

Are Children the Better Placebo Analgesia Responders? An Experimental Approach.

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Wrobel, Nathalie; Fadai, Tahmine; Sprenger, Christian; Hebebrand, Johannes; Wiech, Katja; Bingel, Ulrike

2015-10-01

There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Placebo and antidepressant treatment for major depression

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Hougaard, Esben

2010-01-01

Antidepressant medication is generally considered the primary treatment for major depressive disorders (MDD), but antidepressant treatment has recently approached a crisis with shrinking specific effects and growing placebo responses in current trials. The aim of the paper is to review the placebo...

Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials.

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David Cohen

Full Text Available BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD, obsessive compulsive disorder (OCD and other anxiety disorders (AD-non-OCD. METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD, age (adolescent vs. child, and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms. As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002. Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.

Placebo Response and Practice Effects in Schizophrenia Cognition Trials.

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Keefe, Richard S E; Davis, Vicki G; Harvey, Philip D; Atkins, Alexandra S; Haig, George M; Hagino, Owen; Marder, Stephen; Hilt, Dana C; Umbricht, Daniel

2017-08-01

Patients' previous experience with performance-based cognitive tests in clinical trials for cognitive impairment associated with schizophrenia can create practice-related improvements. Placebo-controlled trials for cognitive impairment associated with schizophrenia are at risk for these practice effects, which can be difficult to distinguish from placebo effects. To conduct a systematic evaluation of the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) in cognitive impairment associated with schizophrenia and to examine which demographic, clinical, and cognitive characteristics were associated with improvement in placebo conditions. A blinded review was conducted of data from 813 patients with schizophrenia who were treated with placebo in 12 randomized placebo-controlled clinical trials conducted mostly in outpatient clinics in North America, Europe, Asia, and Latin America from February 22, 2007, to March 1, 2014. A total of 779 patients provided data for the primary outcome measure at baseline and at least 1 follow-up. Seven trials had prebaseline assessments wherein the patients knew that they were not receiving treatment, allowing a comparison of practice and placebo effects in the same patients. Placebo compared with various experimental drug treatments. Composite score on the MCCB. Of the 813 patients in the study (260 women and 553 men; mean [SD] age, 41.2 [11.5] years), the mean MCCB composite score at baseline was 22.8 points below the normative mean, and the mean (SEM) total change in the MCCB during receipt of placebo was 1.8 (0.2) T-score points (95% CI, 1.40-2.18), equivalent to a change of 0.18 SD. Practice effects in the 7 studies in which there was a prebaseline assessment were essentially identical to the postbaseline placebo changes. Baseline factors associated with greater improvements in the MCCB during receipt of placebo included more depression

Effect of Blinding With a New Pragmatic Placebo Needle

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Liu, Baoyan; Xu, Huanfang; Ma, Rui; Mo, Qian; Yan, Shiyan; Liu, Zhishun

2014-01-01

Abstract Placebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration. We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed. Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers’ perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01–2.64). The influences of age, sex, educational level, acupuncture

Laterality of pain: modulation by placebo and participants' paranormal belief.

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Klemenz, Caroline; Regard, Marianne; Brugger, Peter; Emch, Oliver

2009-09-01

To investigate the effects of placebo and paranormal belief on the laterality of pain perception. The right hemisphere is dominantly involved in both the mediation of pain sensation and the belief in paranormal phenomena. We set out to assess a possible influence of long-term belief systems on placebo analgesia in response to unilateral nociceptive stimuli. Forty healthy participants (20 high and 20 low believers as indexed by the Magical Ideation Scale) underwent a placebo analgesia study measuring stimulus detection, pain threshold, and pain tolerance by electrostimulation on the right and left hand. Placebo treatment consisted of the application of a sham cream on the hands. Placebo had a positive influence on pain perception in the 3 variables. Enhanced pain sensitivity for the left side was only found for the disbelievers. Placebo treatment resulted in a double dissociation: in believers, it increased tolerance exclusively on the left side, in disbelievers on the right side. Our results confirm laterality effects in pain perception. However, only disbelievers conformed to the expected higher left-sided sensitivity. Placebo effects were dissociated between believers and disbelievers suggesting that short-term reactions to a placebo are modulated by a person's long-term belief system.

Placebo prescription and empathy of the physician: A cross-sectional study.

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Braga-Simões, João; Costa, Patrício Soares; Yaphe, John

2017-12-01

Empathy in the patient-physician relationship is a major component in an effective placebo treatment, as in every medical treatment. Understanding the role of empathy of the physician in the placebo effect may help dissect some of the context variables responsible for the effectiveness of the placebo. To determine the frequency of placebo prescription, doctors' beliefs, motivation, and attitudes to placebos in general practice in northern Portugal and to test the association between placebo prescription and physician empathy. A cross-sectional study was conducted between November 2014 and January 2015 among general practice specialists and interns from 14 health centres in a northern Portuguese health region. The self-report questionnaire included the Portuguese version of the Jefferson scale of physician empathy (JSPE) and a questionnaire about placebo prescription. Associations between demographic variables, JSPE score, prescription of placebo, and the attitudes to placebo score were tested with the chi-squared statistic, student t-tests for independent samples, and Pearson correlation. The study included 93 general practitioners (GP) (response rate: 74%). Placebos were prescribed by 73% (n = 68) of the respondents. GPs who prescribe placebo are significantly younger (mean age = 38.4 years; SD = 11.1; t (90) = 2.98, P empathy scores (R = 0.310, P empathy from the prescriber, especially among younger GPs.

Biofeedback for anismus: has placebo effect been overlooked?

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Meagher; Sun; Kennedy; Smart; Lubowski

1999-03-01

Multiple uncontrolled studies have concluded that biofeedback is successful in treating anismus. This study's objective was to assess the physiological effects of placebo and biofeedback treatment on patients with anismus and to correlate changes with clinical improvement. Twelve patients with symptoms and electrophysiological findings of anismus were studied. Initial assessment included a detailed history, symptom assessment by linear analogue scales, anorectal manometric and electrophysiological studies, colon transit scintigraphy, and scintigraphic proctography. Patients underwent 5 days of placebo treatment, followed 1 week later by re-assessment of symptoms and physiological studies. Five days of biofeedback was then given followed by another complete re-assessment 1 week later. A final interview was performed 2 months later. All assessments were by an independent observer who was not responsible for the treatments. Seven patients reported an overall improvement in symptoms following placebo treatment. A total of seven patients reported improvement following biofeedback, three of whom had already reported an improvement with placebo. One patient who reported improvement following placebo had worsening of symptoms following biofeedback. The only symptoms or tests which changed more with biofeedback than placebo were anal pressure and electromyographic activity on attempted defaecation in the left lateral position. There was no demonstrable correlation between change in symptoms and change in physiological tests. The scintigraphic 'ejection fraction' of the rectum was unchanged by treatment. Clinical improvement in previous studies may in part be due to placebo effect and observer bias. Improvement with biofeedback may be due to physiological changes which are not detected with conventional anorectal physiological tests.

Implicit versus explicit associative learning and experimentally induced placebo hypoalgesia

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Andrea L Martin-Pichora

2011-03-01

Full Text Available Andrea L Martin-Pichora1,2, Tsipora D. Mankovsky-Arnold3, Joel Katz11Department of Psychology, York University, Toronto, ON, Canada; 2Centre for Student Development and Counseling, Ryerson University, Toronto, ON, Canada; 3Department of Psychology, McGill University, Montreal, QC, CanadaAbstract: The present study examined whether 1 placebo hypoalgesia can be generated through implicit associative learning (ie, conditioning in the absence of conscious awareness and 2 the magnitude of placebo hypoalgesia changes when expectations about pain are made explicit. The temperature of heat pain stimuli was surreptitiously lowered during conditioning trials for the placebo cream and the magnitude of the placebo effect was assessed during a subsequent set of trials when the temperature was the same for both placebo and control conditions. To assess whether placebo hypoalgesia could be generated from an implicit tactile stimulus, a 2 × 2 design was used with direction of cream application as one factor and verbal information about which cream was being applied as the second factor. A significant placebo effect was observed when participants received verbal information about which cream was being applied but not following implicit conditioning alone. However, 87.5% of those who showed a placebo response as the result of implicit conditioning were able to accurately guess the order of cream application during the final trial, despite a lack of awareness about the sensory manipulation and low confidence in their ratings, suggesting implicit learning in some participants. In summary, implicit associative learning was evident in some participants but it was not sufficient to produce a placebo effect suggesting some level of explicit expectation or cognitive mediation may be necessary. Notably, the placebo response was abolished when expectations were made explicit, suggesting a delicate interplay between attention and expectation.Keywords: placebo hypoalgesia

Motivation and expectancy influences in placebo responding: the mediating role of attention.

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Aigner, Carrie; Svanum, Soren

2014-12-01

Drawing upon research in perception and motivation, the current study proposes a motivation-attention model of placebo in which more motivated persons pay greater attention to placebo-related stimuli, directly influencing placebo response. We manipulated both motivation to respond to placebo and expectations of placebo response in a 2 × 2 design. Participants (N = 152) evaluated a series of placebo pheromones (slightly scented water) of potential romantic dates and made desirability ratings. Consistent with hypotheses, more highly motivated participants demonstrated greater placebo responses, as evidenced by higher desirability ratings of the "pheromone" and greater variability among ratings, when compared to less motivated participants. Moreover, the relation between motivation and placebo response was mediated by attention. Contrary to expectations, we found no effect for expectancy. These findings highlight the importance of motivation and the mediating factor of attention in placebo and support goal-oriented models of placebo. © 2014 International Union of Psychological Science.

[Placebo-controlled trials in schizophrenia].

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Melamed, Yuval; Davidson, Michael; Bleich, Avi

2004-03-01

Clinical trials involving human subjects give rise to ethical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective medications or to placebo. The complexity of the problem increases when dealing with mentally ill patients, for whom, on the one hand there is no known cure for their disease, and on the other hand, it is sometimes questionable whether or not they are able to provide informed consent to participate in clinical trials. The Israel Psychiatric Association decided to develop a position paper on the subject of placebo-controlled clinical trials in schizophrenia patients. Discussion groups were established, and the available material in the professional literature was examined, with an emphasis on recent developments. The Declaration of Helsinki and its amendments were analyzed, and experts in the field were consulted. Clinical drug trials for development of new medications are essential in all fields of medicine, especially in psychiatry. The requirement for a placebo arm in pharmaceutical trials presents ethical and clinical dilemmas that are especially complicated with regard to mentally ill persons whose free choice and ability to provide informed consent may be questionable. However, we do not believe that this predicament justifies unconditional rejection of placebo use in psychiatry, when it may provide substantial benefit for some patients. Simultaneously, it is our duty to provide stringent restrictions that will enable strict supervision over the scientific, clinical and ethical aspects of the trials. We propose the following criteria for approval of pharmaceutical trials that include a placebo arm: scientific justification; clinical and ethical justification; provision of informed consent; recruitment of patients hospitalized voluntarily; prevention of harm; administration of additional potential therapeutic interventions; benefit to patients participating in the study; control and follow

Energyhealing and the placebo-effect

DEFF Research Database (Denmark)

Ostenfeld-Rosenthal, Ann

2012-01-01

and the placebo effect? From a phenomenological perspective and with a point of departure in MUS (medically unexplained symptoms) patients’ experiences of ‘bodily-lived-meaning’ in Danish healing rituals I try to develop an understanding of how bodily experienced images of body and self work to transform...... the patient during a healing ritual, of the process of a bodily founded symbolic ‘re-editing’ of body- and self-image, which I argue is a fundamental art in healing rituals. In conclusion I argue that the placebo is nothing but the effectiveness of bodily sensed symbols....

Can pill placebo augment cognitive-behavior therapy for panic disorder?

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Churchill Rachel

2007-12-01

Full Text Available Abstract Background In a number of drug and psychotherapy comparative trials, psychotherapy-placebo combination has been assumed to represent psychotherapy. Whether psychotherapy plus pill placebo is the same as psychotherapy alone is an empirical question which however has to date never been examined systematically. Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs that directly compared cognitive-behavior therapy (CBT alone against CBT plus pill placebo in the treatment of panic disorder. Results Extensive literature search was able to identify three relevant RCTs. At the end of the acute phase treatment, patients who received CBT plus placebo had 26% (95%CI: 2 to 55% increased chances of responding than those who received CBT alone. At follow-up the difference was no longer statistically significant (22%, 95%CI: -10% to 64%. Conclusion The act of taking a pill placebo may enhance the placebo effect already contained in the effective psychotherapeutic intervention during the acute phase treatment. Theoretically this is an argument against the recently claimed null hypothesis of placebo effect in general and clinically it may point to some further room for enhancing the psychotherapeutic approach for panic disorder.

Placebo Acupuncture Devices: Considerations for Acupuncture Research

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Dan Zhu

2013-01-01

Full Text Available Determining an appropriate control for use in acupuncture research remains one of the largest methodological challenges acupuncture researchers face. In general, acupuncture controls fall under one of two categories: (1 sham acupuncture, in which the skin is punctured with real acupuncture needles either fully at nonacupoint locations or shallowly at acupoint locations or both and (2 placebo acupuncture, which utilizes nonpenetrating acupuncture devices. In this study, we will focus on non-penetrating placebo acupuncture devices (blunted-needle and nonneedle devices that are currently available in acupuncture research. We will describe each device and discuss each device’s validation and application in previous studies. In addition, we will outline the advantages and disadvantages of these devices and highlight how the differences among placebo devices can be used to isolate distinct components of acupuncture treatment and investigate their effects. We would like to emphasize that there is no single placebo device that can serve as the best control for all acupuncture studies; the choice of an acupuncture control should be determined by the specific aim of the study.

Placebo and nocebo effects on itch: effects, mechanisms, and predictors

NARCIS (Netherlands)

Bartels, D.J.P.; Laarhoven, A.I. van; Kerkhof, P.C. van de; Evers, A.W.

2016-01-01

Placebo and nocebo effects have been extensively studied in the field of pain and more recently also on itch. In accordance with placebo research on pain, expectancy learning via verbal suggestion or conditioning has shown to induce placebo and nocebo effects on itch, in which the combination of

Osteoarthritis treatment using autologous conditioned serum after placebo

NARCIS (Netherlands)

Rutgers, Marijn; Creemers, Laura B; Auw Yang, Kiem Gie; Raijmakers, Natasja J H; Dhert, Wouter J A; Saris, Daniel B F

BACKGROUND AND PURPOSE: Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients

A brief history of placebos and clinical trials in psychiatry.

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Shorter, Edward

2011-04-01

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

Placebo and nocebo effects in itch and pain

NARCIS (Netherlands)

Evers, A.W.M.; Bartels, D.J.P.; Laarhoven, A.I.M. van

2014-01-01

Physical complaints, such as pain, can be effectively altered by placebo and nocebo effects due to induction of positive or negative expectations. While verbal suggestion and conditioning are recognized as playing a key role in placebo and nocebo effects on pain, these mechanisms have barely been

Reviving the old sermon of medicine with the placebo effect

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Cho Hyong Jin

2005-01-01

Full Text Available OBJECTIVE: The message of the importance of a caring doctor-patient relationship is now like an old sermon which does not impact anyone's mind or action. Observing the healing practice of the old time physicians, who valued their attitudes and relationship with their patients more than the actual interventions, this paper reviews the literature on their main therapeutic device - the placebo effect - as a novel way of delivering this old sermon of medicine to contemporary doctors. DISCUSSION: There are countless historical and contemporary examples of the impressive placebo effect and although contested by some, it seems real and significant. The classic conditioning theory and the expectation theory explain reasonably well the mechanisms of the placebo effect, especially in conjunction with each other. The underlying biochemical pathway, according to the limited current knowledge, involves endorphins for pain and dopamine for Parkinson's disease. Finally, human factors such as the doctor's positive attitudes and a good doctor-patient relationship seem to be more essential than the placebo itself in eliciting the placebo effect. CONCLUSIONS: Given the body of evidence supporting the existence of significant placebo effect and the importance of the doctor-patient relationship in determining it, the human factors of the medical treatment should be emphasised in order to maximise the placebo effect and consequently the overall therapeutic effect of the healing acts.

Attitudes Toward Placebo Use in Lebanon.

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Abou-Mrad, Fadi; Tarabey, Lubna

2015-05-01

Placebo use, both in clinical trials and patient care, is a problematic ethical issue surrounded by opposing arguments from those who advocate its use versus those who do not. This problematic aspect of placebo is more challenging in Lebanon where religious ideologies dominate people's beliefs, and where laws that guide medical care are vague. This paper aims to highlight the cultural ideologies that dominate medical care and the perspectives of people associated with the field. The method relied on semi-structured interviews with religious leaders, representatives of society and healthcare professionals. Panel discussions incorporating healthcare professionals, academics, scientists and medical researchers were also organized. The legal environment in Lebanon is characterized by lack of an appropriate legislative guideline that categorically clarifies the value of the human person in medical care. There is a lack of a common ethical standard within a society characterized by social and political dissent. The culturally upheld principles and actual application of the principles of ethics surrounding patient autonomy were overviewed. Medical practitioners failed to agree to a general outline that should guide the use of placebo where it became evident that each practitioner adopted a subjective framework which ultimately undermines patient autonomy. The paper proposes that until a new legislative code that clarifies ethical principles properly guiding medical care is coined, the process of placebo use will continue to be subject to the paternalistic assessments of medical professionals. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Is placebo useful in the treatment of major depression in clinical practice?

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Marchesi C

2013-06-01

Full Text Available Carlo Marchesi, Chiara De Panfilis, Matteo Tonna, Paolo Ossola University of Parma, Department of Neuroscience, Psychiatric Unit, Parma, Italy Background: For many years, placebo has been defined by its inert content and use in clinical trials. In recent years, several studies have demonstrated its effect in the treatment of major depression. The aim of this paper is to present the conclusions of recent meta-analyses of the placebo effect in major depression, to explain the mechanism by which placebo exerts its effect, and to discuss whether placebo can be used in the treatment of patients with major depression in clinical practice. Recent meta-analyses have demonstrated that the placebo effect is estimated to account for 67% of the treatment effect in patients receiving antidepressants, and furthermore that placebo is as effective as antidepressants in patients with mild to moderate major depression (reporting a Hamilton Depression Rating Scale score lower than 25, whereas placebo is less effective than antidepressants in severely depressed patients. However, several limitations make the translation of these conclusions into clinical practice impracticable. Clinicians should learn from the "placebo lesson" to maximize the nonspecific effects of treatment when they prescribe an antidepressant, particularly in less severely depressed patients, who show a higher placebo response in randomized controlled trials. This strategy can increase the antidepressant effect and may reduce nonadherence with treatment. Keywords: placebo effect, major depressive disorder, subthreshold depressive disorder, antidepressants

Confusing placebo effect with natural history in epilepsy: A big data approach.

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Goldenholz, Daniel M; Moss, Robert; Scott, Jonathan; Auh, Sungyoung; Theodore, William H

2015-09-01

For unknown reasons, placebos reduce seizures in clinical trials in many patients. It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using Seizuretracker.com, a patient-centered database of 684,825 seizures, we simulated "placebo" and "drug" trials. These simulations were employed to clarify the sources of placebo effects in epilepsy, and to identify methods of diminishing placebo effects. Simulation 1 included 9 trials with a 6-week baseline and 6-week test period, starting at time 0, 3, 6…24 months. Here, "placebo" reduced seizures regardless of study start time. Regression-to-the-mean persisted only for 3 to 6 months. Simulation 2 comprised a 6-week baseline and then 2 years of follow-up. Seizure frequencies continued to improve throughout follow-up. Although the group improved, individuals switched from improvement to worsening and back. Simulation 3 involved a placebo-controlled "drug" trial, to explore methods of placebo response reduction. An efficacious "drug" failed to demonstrate a significant effect compared with "placebo" (p = 0.12), although modifications either in study start time (p = 0.025) or baseline population reduction (p = 0.0028) allowed the drug to achieve a statistically significant effect compared with placebo. In epilepsy clinical trials, some seizure reduction traditionally attributed to placebo effect may reflect the natural course of the disease itself. Understanding these dynamics will allow future investigations into optimal clinical trial design and may lead to identification of more effective therapies. Ann Neurol 2015;78:329-336. © 2015 American Neurological Association.

Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture

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Soyeon Cheon

2018-01-01

Full Text Available Abstract Background While full disclosure of information on placebo control in participant information leaflets (PILs in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes. Methods Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model. Results In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI −0.21 vs. −0.16; p = 0.38. In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference − 0.43 vs. −0.12; p = 0.03, probably due to enhanced expectations. Conclusions How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we

Experimental Cardiac Arrest Treatment with Adrenaline, Vasopressin, or Placebo

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Palácio, Manoel Ângelo Gomes; de Paiva, Edison Ferreira; de Azevedo, Luciano Cesar Pontes; Timerman, Ari

2013-01-01

Background The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. Objectives To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). Methods A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Results Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). Conclusion The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate. PMID:24173134

Should we reconsider the routine use of placebo controls in clinical research?

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Avins Andrew L

2012-04-01

Full Text Available Abstract Background Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. Methods We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. Results We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Conclusions Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

Should we reconsider the routine use of placebo controls in clinical research?

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Avins, Andrew L; Cherkin, Daniel C; Sherman, Karen J; Goldberg, Harley; Pressman, Alice

2012-04-27

Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

Use of Placebo in Supplementation Studies—Vitamin D Research Illustrates an Ethical Quandary

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Leigh A. Frame

2018-03-01

Full Text Available History has shown that without explicit and enforced guidelines, even well-intentioned researchers can fail to adequately examine the ethical pros and cons of study design choices. One area in which consensus does not yet exist is the use of placebo groups in vitamin supplementation studies. As a prime example, we focus on vitamin D research. We aim to provide an overview of the ethical issues in placebo-controlled studies and guide future discussion about the ethical use of placebo groups. Research in the field of vitamin D shows variation in how placebo groups are used. We outline four types of control groups in use: active-control, placebo-control with restrictions on supplementation, placebo-control without supplementation restrictions, and placebo-control with rescue repletion therapy. The first two types highlight discrete ethical issues: active-control trials limit the ability to detect a difference; placebo-control trials that restrict supplementation potentially place subjects at risk of undue harm. The final two, placebo-control without supplementation restrictions or with rescue repletion therapy, offer potential solutions to these ethical challenges. Building on this, guidelines should be established and enforced on the use of placebo in supplementation studies. Furthermore, the field of vitamin D research has the potential to set an example worthy of emulation.

Intravenous dexketoprofen vs placebo for migraine attack in the emergency department: A randomized, placebo-controlled trial.

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Gungor, Faruk; Akyol, Kamil Can; Kesapli, Mustafa; Celik, Ahmet; Karaca, Adeviye; Bozdemir, Mehmet Nuri; Eken, Cenker

2016-02-01

Migraine is a leading headache etiology that frequently presents to the emergency department (ED). In the present study, we aimed to determine the efficacy of dexketoprofen in aborting migraine headaches in the ED. This prospective, randomized, double-blind study was conducted in an ED of a tertiary care hospital using allocation concealment. Patients were allocated into two arms to receive the study drug; 50 mg dexketoprofen in 50 ml saline and 50 ml saline as placebo. Change in pain intensity was measured by the visual analog scale at baseline, both at 30 and 45 minutes after the study medication was administered. Rescue medication requirement and pain relapse were also recorded by a telephone follow-up at 48 hours. A total of 224 patients (112 in each group) were included into the final analysis. Mean age of the study participants was 37 ± 11 (SD) and 25% (n = 56) of them were male. The median pain improvement at 45 minutes for patients receiving dexketoprofen was 55 (IQR: 49 to 60) and 30 (IQR: 25 to 35) for those receiving placebo. The mean difference between the two groups at 45 minutes was 21.4 (95% CI: 14.4. to 28.5). Rescue drugs were needed in 22.3% of patients who received dexketoprofen compared to 55.4% in patients who received placebo (dif: 33.1%; 95% CI: 20% to 45%). There were no adverse events reported in either group during the study period. Intravenous dexketoprofen is superior to placebo in relieving migraine headaches in the ED. It may be a suitable therapy with minimum side effects in patients presenting with a migraine headache to the ED. © International Headache Society 2015.

An algorithm for evaluating the ethics of a placebo-controlled trial.

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Amdur, R J; Biddle, C J

2001-10-20

The purpose of this article is to clarify the decision points that are important to consider when evaluating the ethics of a placebo-controlled trial. The ethical requirements for research involving human subjects are reviewed, and the rationale for and potential problems with concomitant placebo control are explained. A series of case discussions are used to illustrate each decision point. The critical decision points in the evaluation of the ethics of a placebo-controlled trial are as follows: (i) Is placebo being used in place of standard therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity of standard therapy such that patients routinely refuse this treatment? (iv) Could the use of placebo result in severe suffering or irreversible harm? (v) Is the variability in the placebo response such that it is reasonable to consider other options for the control group? (vi) Would a reasonable person with an average degree of altruism and risk aversiveness agree to participate in this study? The algorithm presented in this article gives researchers and research monitors (such as Institutional Review Board members) the tools they need to evaluate the ethics of a study that uses concomitant placebo control. Copyright 2001 Wiley-Liss, Inc.

Placebo and Nocebo Effects in Sexual Medicine: An Experimental Approach.

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Kruger, Tillmann H C; Grob, Carolin; de Boer, Claas; Peschel, Thomas; Hartmann, Uwe; Tenbergen, Gilian; Schedlowski, Manfred

2016-11-16

Few studies have investigated placebo and nocebo effects in a human sexuality context. Studying placebo and nocebo responses in this context may provide insight into their potential to modulate sexual drive and function. To examine such effects in sexual medicine, 48 healthy, male heterosexual participants were divided into four groups. Each group received instruction to expect stimulating effects, no effect, or an inhibitory effect on sexual functions. Only one group received the dopamine agonist cabergoline; all other groups received placebo or nocebo. Modulations in sexual experience were examined through an established experimental paradigm of sexual arousal and masturbation-induced orgasm during erotic film sequences with instruction to induce placebo or nocebo effects. Endocrine data, appetitive, consummatory, and refractory sexual behavior parameters were assessed using the Arizona Sexual Experience Scale (ASEX) and the Acute Sexual Experience Scale (ASES). Results showed increased levels of sexual function after administration of cabergoline with significant effects for several parameters. Placebo effects were induced only to a small degree. No negative effects on sexual parameters in the nocebo condition were noted. This paradigm could induce only small placebo and nocebo effects. This supports the view that healthy male sexual function seems relatively resistant to negative external influences.

How can placebo effects best be applied in clinical practice? A narrative review

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Bystad M

2015-01-01

Full Text Available Martin Bystad,1,2 Camilla Bystad,3 Rolf Wynn1,3 1Division of Addictions and Specialized Psychiatric Services, University Hospital of North Norway, 2Institute of Psychology, 3Institute of Clinical Medicine, Faculty of Health Sciences, Arctic University of Norway, Tromsø, Norway Abstract: Placebo effects are documented in a number of clinical and experimental studies. It is possible to benefit from placebo effects in clinical practice by using them as effects additive to those of documented and effective treatments. The purpose of this paper is to discuss how doctors and other health workers may benefit from placebo effects within an ethical framework. A narrative review of the literature relating to placebo effects in clinical practice was performed. We searched PubMed and selected textbooks on placebo effects for articles and book chapters relating to placebo effects in clinical practice. By drawing on placebo effects, doctors may access patients’ self-healing potentials. In practice, doctors may best benefit from placebo effects by influencing the patient’s expectations through communication. An important principle is to give the patient information stating that a particular treatment is effective, as long as this is based on realistic optimism. A patient-centered style involving elements such as developing trust and respect, exploring the patient’s values, speaking positively about treatments, and providing reassurance and encouragement might aid in activating placebo effects. The total effect of a documented treatment will partly depend on how well the placebo effects have been activated. Thus, placebo effects can be understood as a form of supplemental treatment. Keywords: placebo effects, doctor-patient communication, expectations, biopsychosocial model

Experimental cardiac arrest treatment with adrenaline, vasopressin, or placebo.

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Palácio, Manoel Ângelo Gomes; Paiva, Edison Ferreira de; Azevedo, Luciano Cesar Pontes de; Timerman, Ari

2013-12-01

The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate.

Placebos and painkillers: is mind as real as matter?

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Colloca, Luana; Benedetti, Fabrizio

2005-07-01

Considerable progress has been made in our understanding of the neurobiological mechanisms of the placebo effect, and most of our knowledge originates from the field of pain and analgesia. Today, the placebo effect represents a promising model that could allow us to shed new light on mind-body interactions. The mental events induced by placebo administration can activate mechanisms that are similar to those activated by drugs, which indicates a similarity between psychosocial and pharmacodynamic effects. These new neurobiological advances are already changing our conception of how clinical trials and medical practice must be viewed and conducted.

The use of pure and impure placebo interventions in primary care - a qualitative approach

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Senn Oliver

2011-03-01

Full Text Available Abstract Background Placebos play an important role in clinical trials and several surveys have shown that they are also common in daily practice. Previous research focused primarily on the frequency of placebo use in outpatient care. Our aim was to explore physicians' views on the use of placebos in daily practice, whereby distinction was made between pure placebos (substances with no pharmacological effect, e.g. sugar pills and impure placebos (substances with pharmacological effect but not on the condition being treated, e.g. antibiotics in viral infections or vitamins. Methods We performed semi-structured interviews with a sample of twelve primary care physicians (PCPs. The interview addressed individual definitions of a placebo, attitudes towards placebos and the participants' reasons for prescribing them. The interviews were transcribed and analysed using qualitative content analysis. Results The definition of a placebo given by the majority of the PCPs in our study was one which actually only describes pure placebos. This definition, combined with the fact that most impure placebos were not regarded as placebos at all, means that most of the participating PCPs were not aware of the extent to which placebos are used in daily practice. The PCPs stated that they use placebos (both pure and impure mainly in the case of non-severe diseases for which there was often no satisfactory somatic explanation. According to the PCPs, cases like this are often treated by complementary and alternative therapies and these, too, are associated with placebo effects. However, all PCPs felt that the ethical aspects of such treatment were unclear and they were unsure as to how to communicate the use of placebos to their patients. Most of them would appreciate ethical guidelines on how to deal with this issue. Conclusions Many PCPs seem to be unaware that some of the drugs they prescribe are classified as impure placebos. Perceptions of effectiveness and doubts

A polysomnographic placebo-controlled evaluation of the efficacy and safety of eszopiclone relative to placebo and zolpidem in the treatment of primary insomnia.

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Erman, Milton K; Zammit, Gary; Rubens, Robert; Schaefer, Kendyl; Wessel, Thomas; Amato, David; Caron, Judy; Walsh, James K

2008-06-15

To evaluate the polysomnographic efficacy and the safety of a range of doses of eszopiclone relative to placebo in patients with primary insomnia. Zolpidem 10 mg was included as an active control. This multicenter, randomized, crossover study enrolled patients aged 21-64 years meeting the DSM-IV criteria for primary insomnia (n = 65). Patients received 2 nights treatment each with placebo, eszopiclone 1 mg, 2 mg, 2.5 mg, or 3 mg, and zolpidem 10 mg after randomization to one of 6 treatment sequences. Visits were separated by a 3-7 day washout. Objective efficacy was assessed by polysomnography (PSG). The primary endpoint was latency to persistent sleep (LPS); key secondary endpoints were sleep efficiency (SE) and wake time after sleep onset (WASO); other endpoints included wake time during sleep (WTDS) and number of awakenings (NAW), as well as patient-reported variables. LPS and SE were significantly different than placebo for all active treatments (p zolpidem 10 mg or the other eszopiclone doses. The incidence of central nervous system adverse events was 23.4% for zolpidem 10 mg, 6.2% to 12.5% for the eszopiclone doses, and 7.9% for placebo. Relative to placebo, all active treatments were effective in reducing LPS and increasing SE. Eszopiclone 3 mg was significantly different from placebo on the 3 PSG measures of sleep maintenance (WASO, WTDS, and NAW). Significant differences between zolpidem 10 mg and eszopiclone (2 mg or 3 mg) were not observed for PSG-measured outcomes, although the study was not powered to detect differences between the active drug conditions.

Intervenciones Placebo Para Incrementar el Rendimiento Deportivo: un Tema Revisitado/ Placebo Interventions to Enhance Sports Performance: Revisiting an Issue/ Intervenções Placebo para Aumentar o Rendimento Esportivo: um Tema Revisitado

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Mildreth Larquin-Castillo

2015-05-01

Full Text Available Las intervenciones psicológicas para incrementar el rendimiento de los deportistas han ganado gran popularidad. En este artículo se realizó una revisión de la utilización de intervenciones placebo para potenciar el rendimiento deportivo, a partir de la cual se concluyó que el contexto de aplicación, los rasgos de personalidad del deportista y el ritual de intervención han sido propuestos como los factores más relevantes a tomar en consideración. Se estima que, a pesar de las limitaciones, las intervenciones placebo constituyen alternativas eficaces que tienen distintos modos de aplicación. La utilización de vías conscientes y no-conscientes para activar el efecto placebo se materializa en el empleo de las potencialidades que brindan tanto la sugestión verbal como el priming.

Structural Models Describing Placebo Treatment Effects in Schizophrenia and Other Neuropsychiatric Disorders

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Reddy, Venkatesh Pilla; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; de Greef, Rik; Liu, Jing; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

2011-01-01

Large variation in placebo response within and among clinical trials can substantially affect conclusions about the efficacy of new medications in psychiatry. Developing a robust placebo model to describe the placebo response is important to facilitate quantification of drug effects, and eventually

The placebo effect in sports performance: a brief review.

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Beedie, Christopher J; Foad, Abigail J

2009-01-01

The placebo effect, with its central role in clinical trials, is acknowledged as a factor in sports medicine, although until recently little has been known about the likely magnitude and extent of the effect in any specific research setting. Even less is known about the prevalence of the effect in competitive sport. The present paper reviews 12 intervention studies in sports performance. All examine placebo effects associated with the administration of an inert substance believed by subjects to be an ergogenic aid. Placebo effects of varying magnitudes are reported in studies addressing sports from weightlifting to endurance cycling. Findings suggest that psychological variables such as motivation, expectancy and conditioning, and the interaction of these variables with physiological variables, might be significant factors in driving both positive and negative outcomes. Programmatic research involving the triangulation of data, and investigation of contextual and personality factors in the mediation of placebo responses may help to advance knowledge in this area.

Understanding placebo, nocebo, and iatrogenic treatment effects.

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Bootzin, Richard R; Bailey, Elaine T

2005-07-01

Placebo and nonplacebo treatments have both positive and negative effects on patient outcomes. To better understand the patterning of treatment effects, three specific interventions will be discussed that are reported to produce more harm than benefit: critical incident stress debriefing, group therapy for adolescents with conduct disorders, and psychotherapy for dissociative identity disorder. In each case, there is an interaction between mechanisms thought to underlie both placebo and specific treatment effects. Mechanisms hypothesized to underlie placebo and nocebo effects include patient expectancy, self-focused attention to symptoms, motivation to change, and sociocultural role-enactment cues. In the three treatments discussed, specific mechanisms interact with nonspecific mechanisms to produce iatrogenic effects. To advance knowledge, it is important both to specify the theory of treatment and its expected outcomes and to put the theory to test. Only with attention to the empirical findings from programmatic research of specific and nonspecific effects and their interaction is it possible to improve the outcomes of treatment beyond the status quo.

Attitudes and beliefs about placebo surgery among orthopedic shoulder surgeons in the United Kingdom.

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Karolina Wartolowska

Full Text Available To survey surgeons on their beliefs and attitudes towards the use of placebo in surgery.British orthopedic shoulder surgeons, attending a national conference in the United Kingdom, were asked to complete a self-report online questionnaire about their beliefs and attitudes towards the use of placebo related to surgical intervention. The survey included questions about ethical issues, the mechanism of placebo effects, and any concerns regarding its use.100 surgeons who participated in the survey believed that placebo surgery is ethically acceptable (96%, especially as a part of a clinical trial (46%. Respondents thought that a placebo effect in surgery is real i.e. has a scientific basis (92%, that placebo can be therapeutically beneficial (77%, and that it involves psychological mechanisms (96%. Over half of the respondents (58% have used a surgical procedure with a significant placebo component at least once in their professional career. Their main concern about placebo use in surgery was that it might involve an element of deception.Surgeons generally agreed that a placebo component to surgical intervention might exist. They also supported placebo use in clinical trials and considered it ethical, providing it does not involve deception of patients. More studies are needed, particularly among other surgical specialties and with larger numbers of participants, to better understand the use of placebo in surgery.

Placebo-Controlled Study of Pimozide Augmentation of Fluoxetine in Body Dysmorphic Disorder

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Phillips, Katharine A.

2006-01-01

Objective Although body dysmorphic disorder often responds to serotonin reuptake inhibitors (SRIs), most patients do not respond or respond only partially. However, placebo-controlled studies of augmentation of SRIs have not been done. Furthermore, although 40%–50% of patients are delusional, studies of antipsychotic medications have not been done. Method Twenty-eight patients with body dysmorphic disorder or its delusional variant participated in an 8-week, placebo-controlled, double-blind, parallel-group study of pimozide augmentation of fluoxetine. Results Pimozide was not more effective than placebo: two (18.2%) of 11 subjects responded to pimozide and three (17.6%) of 17 subjects responded to placebo. There was no significant effect of baseline delusionality on endpoint severity of body dysmorphic disorder. Delusionality did not decrease significantly more with pimozide than placebo. Conclusions Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients. Further studies of augmentation for SRIs are needed. PMID:15677604

A systematic review of sex differences in the placebo and the nocebo effect

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Vambheim SM

2017-07-01

Full Text Available Sara M Vambheim,1 Magne Arve Flaten2 1Department of Psychology, UiT, The Arctic University of Norway, Tromsø, 2Department of Psychology, Norwegian University of Science and Technology (NTNU, Trondheim, Norway Objectives: The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect. Methods: A literature search was conducted in multiple electronic databases. Studies were included if the study compared a group or condition where a placebo was administered to a natural history group or similar cohort. Results: Eighteen studies were identified – 12 on placebo effects and 6 on nocebo effects. Chi-square tests revealed that 1 males responded more strongly to placebo treatment, and females responded more strongly to nocebo treatment, and 2 males responded with larger placebo effects induced by verbal information, and females responded with larger nocebo effects induced by conditioning procedures. Conclusion: This review indicates that there are sex differences in the placebo and nocebo effects, probably caused by sex differences in stress, anxiety, and the endogenous opioid system. Keywords: placebo response, nocebo response, placebo analgesia, nocebo hyperalgesia, sex differences

Le cerveau sous effet placebo

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Touzet , Claude

2017-01-01

International audience; Comment le fait de croire qu’on nous injecte de la morphine (alors qu’il s’agit de sérum physiologique) peut-il faire disparaître la douleur ? Investigation sur le cerveau sous placebo.

[Placebo effect: a contribution of social psychology].

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Balez, R; Leroyer, C; Couturaud, F

2014-10-01

This article reviews the psychosocial variables, which are of interest in the relationship between the patient and the physician. According to a classical model of social psychology, such a relationship might contribute to the placebo/nocebo effects. We develop herein various relational and contextual variables, taking into account four dimensions (intra-individual, interpersonal, positional and ideological) and their potential effects on therapeutic responses. This applies both in the setting of daily clinical practice and of clinical trials. The placebo effect offers an opportunity for collaboration and dialogue between social scientists and physicians.

The placebo effect and homeopathy.

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Teixeira, Marcus Z; Guedes, Cristina H F F; Barreto, Patrícia V; Martins, Mílton A

2010-04-01

Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

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Taylor, Jerome H; Landeros-Weisenberger, Angeli; Coughlin, Catherine; Mulqueen, Jilian; Johnson, Jessica A; Gabriel, Daniel; Reed, Margot O; Jakubovski, Ewgeni; Bloch, Michael H

2018-01-01

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

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Norio Sugawara

Full Text Available Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs.The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan.Using a cross-sectional design, we recruited patients (n = 251 aged 47.7±13.2 (mean±SD with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials.The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation.Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold.

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Dockhorn, R; Grossman, J; Posner, M; Zinny, M; Tinkleman, D

1992-12-01

Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003).

Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

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Kathryn T Hall

Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

Is placebo analgesia mediated by endogenous opioids? A systematic review

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ter Riet, G.; de Craen, A. J.; de Boer, Anthonius; Kessels, A. G.

1998-01-01

This systematic review assesses six experimental studies into the mechanism of placebo analgesia in human subjects suffering from clinical pain or experimentally induced ischaemic arm pain. Due to their sophisticated designs, these studies probably provide the best evidence that placebo analgesia

Clinical and ethical implications of placebo effects: enhancing patients' benefits from pain treatment.

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Klinger, Regine; Flor, Herta

2014-01-01

Expectancy and learning are the core psychological mechanisms of placebo analgesia. They interact with further psychological processes such as emotions and motivations (e.g., anxiety, desire for relief), somatic focus, or cognitions (e.g., attitudes toward the treatment). The development of placebo responsiveness and the actual placebo response in a person is the result of the complex interaction between factors traced back to the individual learning history related to analgesic drugs or treatments and factors of the current context referring to the analgesic or placebo treatment. The aim of this chapter is to depict these complex interactions in a new model of analgesic placebo effects. It joins aspects of the learning history (preexisting experiences and preexisting expectations) of a patient with aspects of the current context (current expectation as a result of external and internal situation in which a pain medication/treatment/placebo is taken, e.g., current information about pain medication, current specific context/cues, desire for pain relief, certainty about upcoming pain relief, current expectation about pain reducing course, current selective attention, increased pain experience, or decreased pain experience). In order to exploit placebo efficacy for an analgesic treatment it is worthwhile to assess in which direction each of these factors exerts its influence in order to maximize placebo effects for a specific patient. By applying placebo mechanisms in this differentiated way, the efficacy of pain treatment can be deliberately boosted.

Ulipristal acetate versus placebo for fibroid treatment before surgery.

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Donnez, Jacques; Tatarchuk, Tetyana F; Bouchard, Philippe; Puscasiu, Lucian; Zakharenko, Nataliya F; Ivanova, Tatiana; Ugocsai, Gyula; Mara, Michal; Jilla, Manju P; Bestel, Elke; Terrill, Paul; Osterloh, Ian; Loumaye, Ernest

2012-02-02

The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain. We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of ≤10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women). All patients received iron supplementation. The coprimary efficacy end points were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at week 13, after which patients could undergo surgery. At 13 weeks, uterine bleeding was controlled in 91% of the women receiving 5 mg of ulipristal acetate, 92% of those receiving 10 mg of ulipristal acetate, and 19% of those receiving placebo (P<0.001 for the comparison of each dose of ulipristal acetate with placebo). The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were -21%, -12%, and +3% (P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo, and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo). Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy. Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate (uterine hemorrhage) and in one patient during receipt of placebo (fibroid protruding through the cervix). Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo

Designing a placebo device: involving service users in clinical trial design.

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Gooberman-Hill, Rachael; Jinks, Clare; Bouças, Sofia Barbosa; Hislop, Kelly; Dziedzic, Krysia S; Rhodes, Carol; Burston, Amanda; Adams, Jo

2013-12-01

Service users are increasingly involved in the design of clinical trials and in product and device development. Service user involvement in placebo development is crucial to a credible and acceptable placebo for clinical trials, but such involvement has not yet been reported. To enhance the design of a future clinical trial of hand splints for thumb-base osteoarthritis (OA), service users were involved in splint selection and design of a placebo splint. This article describes and reflects on this process. Two fora of service users were convened in 2011. Service users who had been prescribed a thumb splint for thumb-base OA were approached about involvement by Occupational Therapy (OT) practitioners. A total of eight service users took part in the fora. Service users discussed their experience of OA and their own splints and then tried a variety of alternative splints. Through this they identified the active features of splints alongside acceptable and unacceptable design features. Service users focused on wearability and support with or without immobilization. Fora discussed whether a placebo group ('arm') was an acceptable feature of a future trial, and service users developed a potential design for a placebo splint. This is the first project that to involve service users in placebo design. Service users are increasingly involved in product and device design and are ideally placed to identify features to make a placebo credible yet lacking key active ingredients. The future trial will include research into its acceptability. © 2013 John Wiley & Sons Ltd.

Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomised, placebo-controlled study.

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Oelke, Matthias; Giuliano, François; Baygani, Simin K; Melby, Thomas; Sontag, Angelina

2014-10-01

To assess treatment satisfaction with tadalafil or tamsulosin vs placebo in a 12-week, randomised, double-blind study of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). After a 4-week placebo lead-in period, men aged ≥45 years with an International Prostate Symptom Score (IPSS) of ≥13 and a maximum urinary flow rate of ≥4 to ≤15 mL/s received placebo (172 men), tadalafil 5 mg (171), or tamsulosin 0.4 mg (168) once daily for 12 weeks. Treatment Satisfaction Scale-BPH (TSS-BPH) responses were assessed based on median treatment differences using the van Elteren test. Overall treatment satisfaction was greater for tadalafil vs placebo (P = 0.005), based on greater satisfaction with efficacy (P = 0.003); neither overall treatment satisfaction nor satisfaction with efficacy was greater for tamsulosin vs placebo (P ≥ 0.409). For individual questions, 66.5% of men rated tadalafil treatment as 'effective/very effective' (Question 1, Q1) vs placebo (P = 0.011), 72.6% would 'definitely/probably recommend their treatment' (Q3; P = 0.043), 71.8% were generally 'very satisfied/satisfied with their medication' (Q8; P BPH by baseline age (≤65/>65 years), history of erectile dysfunction (yes/no), LUTS/BPH severity (IPSSplacebo, with only borderline difference for men without prior therapy. Treatment satisfaction was greater with tadalafil vs placebo, with no significant difference between tamsulosin and placebo. © 2014 The Authors. BJU International © 2014 BJU International.

Ethical Overview of Placebo Control in Psychiatric Research - Concepts and Challenges.

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Ćurković, Marko; Živković, Maja; Radić, Krešimir; Vilibić, Maja; Ćelić, Ivan; Bagarić, Dario

2015-06-01

Permissibility of placebo controls in psychiatric research is raising everlasting controversies. The main ethical issue remains: whether, when, under what conditions, and to what extent is it justifiable to disregard subject's present (best) interest for the presumably "greater" ones. In relation to this main ethical concern, two distinct arguments arose: proponents of placebo controls trials (placebo ortxodoxy) and proponents of active controls trials (active-control orthodoxy). More recently, in new ethical guidelines, Declaration of Helsinki and International Ethical Guidelines for Biomedical Research Involving Human Subjects, a "middle way" approach was formulated, acceptable to both sides of the argument, saying placebo controls can be justified under certain conditions: when and only when, they firstly present undisputed methodological reasoning, and secondly, fulfill certain ethical considerations - mainly regarding the permissibility of accompanied risks. These ethical evaluations are inevitably contextual and evoke the need for the principle of proportionality. In scope of recent findings of substantial and progressively increasing placebo response in psychiatric research, contextual factors are identified and both theoretical and practical challenges are discussed.

Placebo use in the United kingdom: results from a national survey of primary care practitioners.

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Jeremy Howick

Full Text Available OBJECTIVES: Surveys in various countries suggest 17% to 80% of doctors prescribe 'placebos' in routine practice, but prevalence of placebo use in UK primary care is unknown. METHODS: We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into 'pure' and 'impure'. 'Impure' placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for suspected viral infections. 'Pure' placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks. RESULTS: We surveyed 1715 general practitioners and 783 (46% completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15 of respondents used pure placebos while 97% (95% CI 96 to 98 used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79 used impure placebos at least once per week. Most (66% for pure, 84% for impure respondents stated placebos were ethical in some circumstances. CONCLUSION AND IMPLICATIONS: Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

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Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

2016-06-01

Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

Placebo-mediated, Naloxone-sensitive suggestibility of short-term memory performance.

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Stern, Jair; Candia, Victor; Porchet, Roseline I; Krummenacher, Peter; Folkers, Gerd; Schedlowski, Manfred; Ettlin, Dominik A; Schönbächler, Georg

2011-03-01

Physiological studies of placebo-mediated suggestion have been recently performed beyond their traditional clinical context of pain and analgesia. Various neurotransmitter systems and immunological modulators have been used in successful placebo suggestions, including Dopamine, Cholecystokinin and, most extensively, opioids. We adhered to an established conceptual framework of placebo research and used the μ-opioid-antagonist Naloxone to test the applicability of this framework within a cognitive domain (e.g. memory) in healthy volunteers. Healthy men (n=62, age 29, SD=9) were required to perform a task-battery, including standardized and custom-designed memory tasks, to test short-term recall and delayed recognition. Tasks were performed twice, before and after intravenous injection of either NaCl (0.9%) or Naloxone (both 0.15 mg/kg), in a double-blind setting. While one group was given neutral information (S-), the other was told that it might receive a drug with suspected memory-boosting properties (S+). Objective and subjective indexes of memory performance and salivary cortisol (as a stress marker) were recorded during both runs and differences between groups were assessed. Short-term memory recall, but not delayed recognition, was objectively increased after placebo-mediated suggestion in the NaCl-group. Naloxone specifically blocked the suggestion effect without interfering with memory performance. These results were not affected when changes in salivary cortisol levels were considered. No reaction time changes, recorded to uncover unspecific attentional impairment, were seen. Placebo-mediated suggestion produced a training-independent, objective and Naloxone-sensitive increase in memory performance. These results indicate an opioid-mediated placebo effect within a circumscribed cognitive domain in healthy volunteers. Copyright © 2011 Elsevier Inc. All rights reserved.

Segregating the cerebral mechanisms of antidepressants and placebo in fibromyalgia.

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Jensen, Karin B; Petzke, Frank; Carville, Serena; Choy, Ernest; Fransson, Peter; Gracely, Richard H; Vitton, Olivier; Marcus, Hanke; Williams, Steven C R; Ingvar, Martin; Kosek, Eva

2014-12-01

Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology. This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain. Copyright © 2014 American Pain Society. Published by

A Machine Learning Approach to Identifying Placebo Responders in Late-Life Depression Trials.

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Zilcha-Mano, Sigal; Roose, Steven P; Brown, Patrick J; Rutherford, Bret R

2018-01-11

Despite efforts to identify characteristics associated with medication-placebo differences in antidepressant trials, few consistent findings have emerged to guide participant selection in drug development settings and differential therapeutics in clinical practice. Limitations in the methodologies used, particularly searching for a single moderator while treating all other variables as noise, may partially explain the failure to generate consistent results. The present study tested whether interactions between pretreatment patient characteristics, rather than a single-variable solution, may better predict who is most likely to benefit from placebo versus medication. Data were analyzed from 174 patients aged 75 years and older with unipolar depression who were randomly assigned to citalopram or placebo. Model-based recursive partitioning analysis was conducted to identify the most robust significant moderators of placebo versus citalopram response. The greatest signal detection between medication and placebo in favor of medication was among patients with fewer years of education (≤12) who suffered from a longer duration of depression since their first episode (>3.47 years) (B = 2.53, t(32) = 3.01, p = 0.004). Compared with medication, placebo had the greatest response for those who were more educated (>12 years), to the point where placebo almost outperformed medication (B = -0.57, t(96) = -1.90, p = 0.06). Machine learning approaches capable of evaluating the contributions of multiple predictor variables may be a promising methodology for identifying placebo versus medication responders. Duration of depression and education should be considered in the efforts to modulate placebo magnitude in drug development settings and in clinical practice. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Placebo Mechanisms of Manual Therapy: A Sheep in Wolf's Clothing?

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Bialosky, Joel E; Bishop, Mark D; Penza, Charles W

2017-05-01

When a physical therapist provides a manual therapy (MT) intervention for a patient presenting with pain and the patient experiences a positive clinical outcome, we cannot answer as to why this occurs. Would we continue to devote valuable time and financial resources to learning and improving our skills in providing MT interventions if the related clinical outcomes were placebo responses? In this Viewpoint, the authors conceptualize placebo as an active and important mechanism of MT and argue that placebo mechanisms deserve consideration as an important component of the treatment effect. J Orthop Sports Phys Ther 2017;47(5):301-304. doi:10.2519/jospt.2017.0604.

Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism.

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Kahaly, George J; Riedl, Michaela; König, Jochem; Diana, Tanja; Schomburg, Lutz

2017-11-01

Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Evaluate efficacy of add-on Se on medical treatment in GD. Double-blind, placebo-controlled, randomized supplementation trial. Academic endocrine outpatient clinic. Seventy untreated hyperthyroid patients with GD. Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Response rate (week 24), recurrence rate (week 36), and safety. A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24 [odds ratio (OR) 0.93; 95% confidence interval (CI), 0.26 to 3.25; P = 0.904] in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13; 95% CI, 0.29 to 2.66; P = 0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85; 95% CI, 0.31 to 2.32; P = 0.80). Serum levels of free triiodothyronine/free tetraiodothyronine, thyroid-stimulating hormone receptor antibody, prevalence of moderate to severe Graves orbitopathy, thyroid volume, and MMI starting dose were significantly lower in responders than in nonresponders. A total of 56 and 63 adverse events occurred in the Se and placebo groups, respectively (P = 0.164), whereas only one drug-related side effect (2.9%) was noted in 35 patients on placebo + MMI. Supplemental Se did not affect response or recurrence rates in GD. Copyright © 2017 Endocrine Society

Physical dependence increases the relative reinforcing effects of caffeine versus placebo.

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Garrett, B E; Griffiths, R R

1998-10-01

Using a within-subject cross-over design, this study examined the role of physical dependence in caffeine reinforcement by experimentally manipulating physical dependence. Each subject was exposed to two chronic drug phases (300 mg/70 kg/day caffeine and placebo) for 9-12 days, with order of phases counterbalanced across subjects. On 2 separate days immediately following each of the chronic drug exposures, subjects received acute doses of either caffeine (300 mg/70 kg) or placebo in counterbalanced order. The reinforcing effects of these drugs were then determined by using a multiple-choice procedure in which subjects made a series of discrete choices between receiving varying amounts of money or receiving the drug again, and a choice between the two drugs. To ensure that subjects completed the form carefully, following exposure to both of the acute drug administrations, one of the subject's previous choices from the multiple-choice form was randomly selected and the consequence of that choice was implemented. When subjects were maintained on chronic caffeine, they were willing to forfeit significantly more money and showed significant increases in typical withdrawal symptoms (e.g. fatigue, mood disturbance) after receiving placebo as compared to the other three conditions. When subjects were maintained on chronic caffeine, they also chose to receive caffeine over placebo twice as often than when they were maintained on chronic placebo. These findings provide the strongest evidence to date indicating that caffeine physical dependence increases the relative reinforcing effects of caffeine versus placebo.

Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

NARCIS (Netherlands)

Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

2014-01-01

Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST).

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Pressman, Alice; Avins, Andrew L; Neuhaus, John; Ackerson, Lynn; Rudd, Peter

2012-05-01

Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality. Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality. Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication over the entire course of each individual's participation in the study, while those with "lower placebo adherence" took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables. Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR=0.61, 95% Confidence Interval: 0.46-0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations. Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation. Copyright © 2012 Elsevier Inc. All rights reserved.

Mechanisms of placebo analgesia: A dual-process model informed by insights from cross-species comparisons.

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Schafer, Scott M; Geuter, Stephan; Wager, Tor D

2018-01-01

Placebo treatments are pharmacologically inert, but are known to alleviate symptoms across a variety of clinical conditions. Associative learning and cognitive expectations both play important roles in placebo responses, however we are just beginning to understand how interactions between these processes lead to powerful effects. Here, we review the psychological principles underlying placebo effects and our current understanding of their brain bases, focusing on studies demonstrating both the importance of cognitive expectations and those that demonstrate expectancy-independent associative learning. To account for both forms of placebo analgesia, we propose a dual-process model in which flexible, contextually driven cognitive schemas and attributions guide associative learning processes that produce stable, long-term placebo effects. According to this model, the placebo-induction paradigms with the most powerful effects are those that combine reinforcement (e.g., the experience of reduced pain after placebo treatment) with suggestions and context cues that disambiguate learning by attributing perceived benefit to the placebo. Using this model as a conceptual scaffold, we review and compare neurobiological systems identified in both human studies of placebo analgesia and behavioral pain modulation in rodents. We identify substantial overlap between the circuits involved in human placebo analgesia and those that mediate multiple forms of context-based modulation of pain behavior in rodents, including forebrain-brainstem pathways and opioid and cannabinoid systems in particular. This overlap suggests that placebo effects are part of a set of adaptive mechanisms for shaping nociceptive signaling based on its information value and anticipated optimal response in a given behavioral context. Copyright © 2017 Elsevier Ltd. All rights reserved.

The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

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Walach Harald

2005-08-01

Full Text Available Abstract Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.

The challenge of recruiting patients into a placebo-controlled surgical trial

DEFF Research Database (Denmark)

Hare, Kristoffer B; Lohmander, L Stefan; Roos, Ewa M.

2014-01-01

BACKGROUND: Randomized placebo-controlled trials represent the gold standard in evaluating healthcare interventions but are rarely performed within orthopedics. Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo...

Another face of placebo: The lessebo effect in Parkinson disease

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Mestre, Tiago A.; Shah, Prakesh; Marras, Connie; Tomlinson, George

2014-01-01

Objective: To study the impact of negative expectation related to receiving a placebo (the “lessebo effect”) on efficacy outcome measures of symptomatic treatments in Parkinson disease (PD). Methods: We conducted meta-analyses of double-blind randomized controlled trials (RCTs) of dopamine agonists in PD and compared the pooled mean score change of the motor section of the Unified Parkinson's Disease Rating Scale (mUPDRS) across active treatment arms according to the presence of a placebo arm or the probability of placebo assignment (0%, <50%, and 50%) of the original RCT. A mixed-effects model was used. Heterogeneity was assessed by subgroup analyses and meta-regression modeling. Results: A total of 28 study arms were extracted from active-controlled trials (3,277 patients) and 42 from placebo-controlled trials (4,554 patients). The overall difference between groups in the pooled mean score change in the mUPDRS was 1.6 units (95% confidence interval [CI] 0.2, 3.0; p = 0.023), in favor of the active-controlled group. In subgroup analyses, this difference was of higher magnitude in the early PD group without motor fluctuations (3.3 mUPDRS units, 95% CI 1.1, 5.4; p = 0.003) and for study duration ≤12 weeks (4.1 mUPDRS units, 95% CI 1.0, 7.2; p = 0.009). There was no between-group difference using probability of placebo assignment as criterion. Conclusions: This study shows that the use of a placebo can be associated with a clinically significant reduction in the magnitude of change of the mUPDRS after an active treatment in RCTs for PD. These new findings have potential implications in the development of new treatments and appraisal of current treatment options for PD and possibly for other neurologic disorders. PMID:24658930

Acute psychological benefits of exercise: reconsideration of the placebo effect.

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Szabo, Attila

2013-10-01

The psychological benefits of exercise are repeatedly and consistently reported in the literature. Various forms of exercise, varying in duration and intensity, yield comparably positive changes in affect, which sheds doubt on the significance of exercise characteristics in the acute mental health benefits resulting from physical activity. Based on research evidence, it is argued that the placebo effect may play a key role in the subjective exercise experience. This report is aimed at highlighting those aspects of the extant literature that call for the reconsideration of the placebo effect in the understanding of the acute mental benefits of physical activity. This narrative review focuses on research evidence demonstrating that the duration and intensity of physical activity are not mediatory factors in the mental health benefits of acute exercise. Current research evidence pointing to the roles of expectancy and conditioning in the affective benefits of exercise calls for the reconsideration of the placebo effect. The present evaluation concludes that new research effort ought to be invested in the placebo-driven affective beneficence of exercise.

A placebo-controlled trial of itopride in functional dyspepsia.

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Holtmann, Gerald; Talley, Nicholas J; Liebregts, Tobias; Adam, Birgit; Parow, Christopher

2006-02-23

The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with anti-acetylcholinesterase [corrected] effects, in patients with functional dyspepsia. Patients with functional dyspepsia were randomly assigned to receive either itopride (50, 100, or 200 mg three times daily) or placebo. After eight weeks of treatment, three primary efficacy end points were analyzed: the change from baseline in the severity of symptoms of functional dyspepsia (as assessed by the Leeds Dyspepsia Questionnaire), patients' global assessment of efficacy (the proportion of patients without symptoms or with marked improvement), and the severity of pain or fullness as rated on a five-grade scale. We randomly assigned 554 patients; 523 had outcome data and could be included in the analyses. After eight weeks, 41 percent of the patients receiving placebo were symptom-free or had marked improvement, as compared with 57 percent, 59 percent, and 64 percent receiving itopride at a dose of 50, 100, or 200 mg three times daily, respectively (Pitopride). Although the symptom score improved significantly in all four groups, an overall analysis revealed that itopride was significantly superior to placebo, with the greatest symptom-score improvement in the 100- and 200-mg groups (-6.24 and -6.27, vs. -4.50 in the placebo group; P=0.05). Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo (73 percent vs. 63 percent, P=0.04). Itopride significantly improves symptoms in patients with functional dyspepsia. (ClinicalTrials.gov number, NCT00272103.). Copyright 2006 Massachusetts Medical Society.

Placebo-suggestion modulates conflict resolution in the Stroop Task.

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Pedro A Magalhães De Saldanha da Gama

Full Text Available Here, we ask whether placebo-suggestion (without any form of hypnotic induction can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a "brain wave" machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion. We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion's contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion.

Placebo effect studies are susceptible to response bias and to other types of biases

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Hróbjartsson, Asbjørn; Kaptchuk, Ted J; Miller, Franklin G

2011-01-01

Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo....

Double-blind clonazepam vs placebo in panic disorder treatment

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VALENÇA ALEXANDRE MARTINS

2000-01-01

Full Text Available OBJECTIVE: To assess the effectiveness of clonazepam, in a fixed dose (2 mg/day, compared with placebo in the treatment of panic disorder patients. METHOD: 24 panic disorder patients with agoraphobia were randomly selected. The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were randomly assigned to either treatment with clonazepam (2 mg/day or placebo, during 6 weeks. Efficacy assessments included: change from baseline in the number of panic attacks; CGI scores for panic disorder; Hamilton rating scale for anxiety; and panic associated symptoms scale. RESULTS: At the therapeutic endpoint, only one of 9 placebo patients (11.1% were free of panic attacks, compared with 8 of 13 (61.5% clonazepam patients (Fisher exact test; p=0,031. CONCLUSION: the results provide evidence for the efficacy of clonazepam in panic disorder patients.

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

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Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

2017-07-01

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

Randomized, Multicenter, Placebo-Controlled Clinical Trial of Duloxetine Versus Placebo for Aromatase Inhibitor-Associated Arthralgias in Early-Stage Breast Cancer: SWOG S1202.

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Henry, N Lynn; Unger, Joseph M; Schott, Anne F; Fehrenbacher, Louis; Flynn, Patrick J; Prow, Debra M; Sharer, Carl W; Burton, Gary V; Kuzma, Charles S; Moseley, Anna; Lew, Danika L; Fisch, Michael J; Moinpour, Carol M; Hershman, Dawn L; Wade, James L

2018-02-01

Purpose Adherence to aromatase inhibitor (AI) therapy for early-stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is US Food and Drug Administration approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Methods This randomized, double-blind, phase III trial included AI-treated postmenopausal women with early-stage breast cancer and who had average joint pain score of ≥ 4 out of 10 that developed or worsened since AI therapy initiation. Patients were randomly assigned 1:1 to duloxetine or placebo for 13 weeks. The primary end point was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score of 4 to 6 v 7 to 10 and prior taxane use). Clinically significant change in average pain was defined as a ≥ 2-point decrease from baseline. Results Of 299 enrolled patients, 127 patients treated with duloxetine and 128 who received placebo were evaluable for the primary analysis. By 12 weeks, the average joint pain score was 0.82 points lower for patients who received duloxetine compared with those who received placebo (95% CI, -1.24 to -0.40; P = .0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events of any grade were higher in the duloxetine-treated group (78% v 50%); rates of grade 3 adverse events were similar. Conclusion Results of treatment with duloxetine for AIMSS were superior to those of placebo among women with early-stage breast cancer, although it resulted in more frequent low-grade toxicities.

Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

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Campbell, M K; Entwistle, V A; Cuthbertson, B H; Skea, Z C; Sutherland, A G; McDonald, A M; Norrie, J D; Carlson, R V; Bridgman, S

2011-02-21

Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this

Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

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McDonald AM

2011-02-01

Full Text Available Abstract Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons; plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists; three focus groups with anaesthetists (one national, two regional; 58 anaesthetists; two focus groups with members of the patient organisation Arthritis Care (7 participants; telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants; interviews with Chairs of UK ethics committees (6 individuals; postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists; two centre pilot (49 patients assessed. Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions proved easier than the method of anaesthesia (general anaesthesia. General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about

Is the perceived placebo effect comparable between adults and children? A meta-regression analysis.

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Janiaud, Perrine; Cornu, Catherine; Lajoinie, Audrey; Djemli, Amina; Cucherat, Michel; Kassai, Behrouz

2017-01-01

A potential larger perceived placebo effect in children compared with adults could influence the detection of the treatment effect and the extrapolation of the treatment benefit from adults to children. This study aims to explore this potential difference, using a meta-epidemiological approach. A systematic review of the literature was done to identify trials included in meta-analyses evaluating a drug intervention with separate data for adults and children. The standardized mean change and the proportion of responders (binary outcomes) were used to calculate the perceived placebo effect. A meta-regression analysis was conducted to test for the difference between adults and children of the perceived placebo effect. For binary outcomes, the perceived placebo effect was significantly more favorable in children compared with adults (β = 0.13; P = 0.001). Parallel group trials (β = -1.83; P < 0.001), subjective outcomes (β = -0.76; P < 0.001), and the disease type significantly influenced the perceived placebo effect. The perceived placebo effect is different between adults and children for binary outcomes. This difference seems to be influenced by the design, the disease, and outcomes. Calibration of new studies for children should consider cautiously the placebo effect in children.

Effects of ginger and expectations on symptoms of nausea in a balanced placebo design.

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Katja Weimer

Full Text Available OBJECTIVE: Ginger effects on (experimental nausea have been described, but also strong placebo effects and sex differences when nausea is involved. The "balanced placebo design" has been proposed to allow better separation of drug and placebo effects. METHODS: Sixty-four healthy participants (32 women were randomly assigned to receive an antiemetic ginger preparation or placebo, and half of each group was told to have received drug or placebo. They were exposed to 5×2 min body rotations to induce nausea. Subjective symptoms and behavioral (rotation tolerance, head movements and physiological measures (electrogastrogram, cortisol were recorded. Groups were balanced for sex of participants and experimenters. RESULTS: Ginger and the information given did not affect any outcome measure, and previous sex differences could not be confirmed. Adding the experimenters revealed a significant four-factorial interaction on behavioral but not on subjective or physiological measures Men who received placebo responded to placebo information when provided by the male experimenter, and to ginger information when provided by the female experimenter. This effect was not significant in women. CONCLUSION: The effects of an antiemetic drug and provided information interact with psychosocial variables of participants and experimenters in reports of nausea.

Design Dilemma: The Debate over Using Placebos in Cancer Clinical Trials

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Many patients and researchers assert that in cancer clinical trials, placebos are inappropriate and that all participants should receive active treatment. But with the emergence of molecularly targeted anticancer agents, some cancer researchers believe placebo-controlled trials are now feasible and, in some cases, necessary.

Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double-blinded, multicenter intervention trial.

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Malay, D Scot; Pressman, Martin M; Assili, Amir; Kline, Jason T; York, Shane; Buren, Ben; Heyman, Eugene R; Borowsky, Pam; LeMay, Carley

2006-01-01

Extracorporeal shockwave therapy (ESWT) has demonstrated efficacy in the treatment of recalcitrant proximal plantar fasciitis. The objective of this investigation was to compare the outcomes of participants treated with a new ESWT device with those treated with placebo. A total of 172 volunteer participants were randomized in a 2:1 active-to-placebo ratio in this prospective, double-blind, multicenter trial conducted between October 2003 and December 2004. ESWT (n=115) or placebo control (n=57) was administered on a single occasion without local or systemic anesthesia or sedation, after which follow-up was undertaken. The primary outcomes were the blind assessor's objective, and the participant's subjective assessments of heel pain during the first 3 months of follow-up. Participants were also followed up to 1 year to identify any adverse outcomes that may have been related to the shockwave device. On the visual analog scale, the blind assessor's objective assessment of heel pain displayed a mean reduction of 2.51 in the shockwave group and 1.57 in the placebo group; this difference was statistically significant (P=.045). On the visual analog scale, the participant's self-assessment of heel pain displayed a mean reduction of 3.39 in the shockwave group and 1.78 in the placebo group; this difference was statistically significant (P<.001). No serious adverse events were observed at any time. It was concluded that ESWT was both efficacious and safe for participants with chronic proximal plantar fasciitis that had been unresponsive to exhaustive conservative treatment.

Placebo Sleep Affects Cognitive Functioning

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Draganich, Christina; Erdal, Kristi

2014-01-01

The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

Placebo versus "standard" hypnosis rationale: attitudes, expectancies, hypnotic responses, and experiences.

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Accardi, Michelle; Cleere, Colleen; Lynn, Steven Jay; Kirsch, Irving

2013-10-01

In this study participants were provided with either the standard rationale that accompanies the Harvard Group Scale of Hypnotic Susceptibility: A (Shor & Orne, 1962) or a rationale that presented hypnosis as a nondeceptive placebo, consistent with Kirsch's (1994) sociocognitive perspective of hypnosis. The effects of the placebo and standard rationales were highly comparable with respect to hypnotic attitudes; prehypnotic expectancies; objective, subjective, and involuntariness measures of hypnotic responding; as well as a variety of subjective experiences during hypnosis, as measured by the Phenomenology of Consciousness Inventory (Pekala, 1982). Differences among correlations were not evident when measures were compared across groups. However, indices of hypnotic responding were correlated with attitudes in the hypnosis but not the placebo condition, and, generally speaking, the link between subjective experiences during hypnosis and measures of hypnotic responding were more reliable in the placebo than the hypnosis group. Researcher findings are neutral with respect to providing support for altered state versus sociocognitive models of hypnosis.

Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study Clonixinato de lisina oral para o tratamento agudo da migrânea: estudo duplo-cego e placebo-controlado

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Abouch V. Krymchantowski

2001-03-01

Full Text Available Several oral nonsteroidal anti-inflammatory drugs (NSAIDs are effective to treat migraine attacks. Lysine clonixinate (LC is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.Alguns antinflamatórios não esteroidais (AINEs são eficazes para o tratamento de crises de migrânea. O clonixinato de lisina (CL é um AINE derivado do ácido nicotínico comprovadamente eficaz no tratamento de várias síndromes dolorosas como a cólica renal e a dor muscular. O objetivo deste estudo duplo-cego placebo-controlado foi avaliar a eficácia do CL oral comparado ao placebo no tratamento agudo da migrânea. Sessenta e quatro pacientes com o diagnóstico de migrânea, de acordo com os critérios da Sociedade Internacional de Cefaléia (IHS, foram estudados prospectivamente. Os pacientes receberam CL ou placebo quando a cefaléia atingiu a intensidade moderada ou severa em 6 crises consecutivas. Para as crises moderadas, o CL foi superior ao placebo em 1, 2 e 4

Cognitive Schemas in Placebo and Nocebo Responding: Role of Autobiographical Memories and Expectations.

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Bartels, Danielle J P; van Laarhoven, Antoinette I M; Heijmans, Naomi; Hermans, Dirk; Debeer, Elise; van de Kerkhof, Peter C M; Evers, Andrea W M

2017-03-01

Placebo effects are presumed to be based on one's expectations and previous experience with regard to a specific treatment. The purpose of this study was to investigate the role of the specificity and valence of memories and expectations with regard to itch in experimentally induced placebo and nocebo itch responses. It was expected that cognitive schemas with more general and more negative memories and expectations with regard to itch contribute to less placebo itch responding. Validated memory tasks (ie, the Autobiographical Memory Test and the Self-referential Endorsement and Recall Task) and expectation tasks (ie, Future Event Task and the Self-referential Endorsement and Recall Task) were modified for physical symptoms, including itch. Specificity and valence of memories and expectations were assessed prior to a placebo experiment in which expectations regarding electrical itch stimuli were induced in healthy participants. Participants who were more specific in their memories regarding itch and who had lesser negative itch-related expectations for the future were more likely to be placebo itch responders. There were no significant differences in effects between the nocebo responders and nonresponders. The adapted tasks for assessing cognitive (memory and expectations) schemas on itch seem promising in explaining interindividual differences in placebo itch responding. Future research should investigate whether similar mechanisms apply to patients with chronic itch. This knowledge can be used for identifying patients who will benefit most from the placebo component of a treatment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Double-blind, placebo-controlled food challenge with apple

DEFF Research Database (Denmark)

Skamstrup Hansen, K; Vestergaard, H; Stahl Skov, P

2001-01-01

The aim of the study was to develop and evaluate different methods of double-blind, placebo-controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, and freeze-dried apple powder. All challenges were performed outside...... frequency of reactions to placebo, probably due to the ingredients used for blinding. The sensitivity of the models with freshly grated apple and freeze-dried apple powder was 0.74/0.60. An increase in sensitivity is desirable. The freeze-dried apple powder proved to be useful for SPT, HR, and oral...

A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis

DEFF Research Database (Denmark)

Falah, M; Madsen, C; Holbech, J V

2012-01-01

sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well....... Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample...... of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non...

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

NARCIS (Netherlands)

Jairath, Vipul; Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D'Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

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Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

2017-10-03

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

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Robb, Adelaide; Bose, Anjana

2013-01-01

Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were

The use of placebo control in clinical trials: An overview of the ...

African Journals Online (AJOL)

The use of placebo control in clinical trials: An overview of the ethical issues involved for the protection of human research participants. ... A placebo looks exactly like the experimental drugs in every respect both in appearance and wrappings ...

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration

DEFF Research Database (Denmark)

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-01-01

groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications...... with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). Results The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0–2), 0.5% (0–1%). We identified...

Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings.

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Linnman, Clas; Catana, Ciprian; Petkov, Mike P; Chonde, Daniel Burje; Becerra, Lino; Hooker, Jacob; Borsook, David

2018-01-01

Pain interventions with no active ingredient, placebo, are sometimes effective in treating chronic pain conditions. Prior studies on the neurobiological underpinnings of placebo analgesia indicate endogenous opioid release and changes in brain responses and functional connectivity during pain anticipation and pain experience in healthy subjects. Here, we investigated placebo analgesia in healthy subjects and in interictal migraine patients (n = 9) and matched healthy controls (n = 9) using 11 C-diprenoprhine Positron Emission Tomography (PET) and simultaneous functional Magnetic Resonance Imaging (fMRI). Intravenous saline injections (the placebo) led to lower pain ratings, but we did not find evidence for an altered placebo response in interictal migraine subjects as compared to healthy subjects.

Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings

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Clas Linnman

2018-01-01

Full Text Available Pain interventions with no active ingredient, placebo, are sometimes effective in treating chronic pain conditions. Prior studies on the neurobiological underpinnings of placebo analgesia indicate endogenous opioid release and changes in brain responses and functional connectivity during pain anticipation and pain experience in healthy subjects. Here, we investigated placebo analgesia in healthy subjects and in interictal migraine patients (n = 9 and matched healthy controls (n = 9 using 11C-diprenoprhine Positron Emission Tomography (PET and simultaneous functional Magnetic Resonance Imaging (fMRI. Intravenous saline injections (the placebo led to lower pain ratings, but we did not find evidence for an altered placebo response in interictal migraine subjects as compared to healthy subjects.

Evaluation of flurazepam and placebo on sleep disorders in childhood

OpenAIRE

Reimão, Rubens; Lefévre, Antonio B.

1982-01-01

The clinically observed results in 40 patients, from 1 to 15 years old, presenting sleep disturbances, in a comparative and statistically approached study of flurazepam 15mg daily against placebo, are reported. Placebo was administered, followed by the drug, during 14 days each. The chief complaints were sleepwalking, sleep-talking, sleep terror, sleep-related bruxism, sleep-related headbanging, insomnia and excessive movements during sleep. A significant effect of flurazepam on sleepwalking,...

A double-blind comparison of fluvoxamine versus placebo in the treatment of compulsive buying disorder.

Science.gov (United States)

Black, D W; Gabel, J; Hansen, J; Schlosser, S

2000-12-01

Nondepressed outpatients with a compulsive buying disorder were recruited by advertisement and word of mouth for inclusion in a controlled treatment trial. Following a 1-week single-blind placebo washout, subjects were randomly assigned to fluvoxamine (n = 12) or placebo (n = 11). Subjects received fluvoxamine (up to 300 mg daily) or placebo for 9 weeks. There were few dropouts. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale--Shopping Version (YBOCS-SV), three Clinical Global Impressions (CGI) ratings, the Hamilton Rating Scale for Depression (HRSD), and the Maudsley Obsessive-compulsive Inventory (MOI). At the conclusion of the trial, 50% of fluvoxamine recipients and 63.6% of placebo recipients achieved CGI ratings of "much" or "very much" improvement, while 33% of fluvoxamine recipients were "very much" improved compared with 18% of placebo recipients (by endpoint analysis). Subjects in both treatment cells showed improvement as early as the second week of the trial, and for most, improvement continued during the 9-week study. There were no significant differences between fluvoxamine- and placebo-treated subjects on any of the outcome measures, with the exception that fluvoxamine recipients achieved greater improvement than placebo recipients on the MOI (p = .02). Adverse experiences were more frequent in the group receiving fluvoxamine, particularly nausea, insomnia, decreased motivation, and sedation. We conclude that in a short-term treatment trial of compulsive buying, subjects receiving fluvoxamine or placebo respond similarly.

Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo.

Science.gov (United States)

Ohls, Robin K; Kamath-Rayne, Beena D; Christensen, Robert D; Wiedmeier, Susan E; Rosenberg, Adam; Fuller, Janell; Lacy, Conra Backstrom; Roohi, Mahshid; Lambert, Diane K; Burnett, Jill J; Pruckler, Barbara; Peceny, Hannah; Cannon, Daniel C; Lowe, Jean R

2014-06-01

We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs. We performed a randomized, masked, multicenter study comparing Darbe (10 μg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/week) given through 35 weeks' postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months' corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed. Of the original 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 ± 7.3; mean ± SD) and Epo recipients (97.9 ± 14.3) compared with placebo recipients (88.7 ± 13.5; P = .01 vs ESA recipients) as was object permanence (P = .05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P < .001). No differences among groups were found in visual or hearing impairment. Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants. Copyright © 2014 by the American Academy of Pediatrics.

Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study.

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Krymchantowski, A V; Barbosa, J S; Cheim, C; Alves, L A

2001-03-01

Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.

Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

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Tania Cursino de Menezes Couceiro

2015-06-01

Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

Seeing is believing: Impact of social modeling on placebo and nocebo responding.

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Faasse, Kate; Grey, Andrew; Jordan, Rachel; Garland, Stacie; Petrie, Keith J

2015-08-01

This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect. It also investigated whether medication branding (brand or generic labeling) moderated social modeling effects. Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications (actually placebos) on preexamination anxiety. After taking the medication, participants were randomized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication. Differences in symptom reporting, blood pressure, heart rate, and anxiety were assessed between the social modeling of side effects and no modeling groups. Seeing a female confederate report side effects reduced the placebo effect in systolic (p = .009) and diastolic blood pressure (p = .033). Seeing a female confederate report side effects also increased both total reported symptoms (mean [SE] 7.35 [.54] vs. 5.16 [0.53] p = .005) and symptoms attributed to the medication (5.27 [0.60] vs. 3.04 [0.59] p = .01), although the effect on symptoms was only seen in female participants. Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group. Social modeling did not affect heart rate or anxiety. Medication branding did not influence placebo or nocebo outcomes. The social modeling of symptoms can substantially reduce or eliminate the placebo effect. Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females. (c) 2015 APA, all rights reserved).

Measurement of event-related potentials and placebo

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Sovilj Platon

2014-01-01

Full Text Available ERP is common abbreviation for event-related brain potentials, which are measured and used in clinical practice as well as in research practice. Contemporary studies of placebo effect are often based on functional neuromagnetic resonance (fMRI, positron emission tomography (PET, and event related potentials (ERP. This paper considers an ERP instrumentation system used in experimental researches of placebo effect. This instrumentation system can be divided into four modules: electrodes and cables, conditioning module, digital measurement module, and PC module for stimulations, presentations, acquisition and data processing. The experimental oddball paradigm is supported by the software of the instrumentation. [Projekat Ministarstva nauke Republike Srbije, br. TR32019 and Provincial Secretariat for Science and Technological Development of Autonomous Province of Vojvodina (Republic of Serbia under research grant No. 114-451-2723

Evaluation of Isosorbide Mononitrate for Preinduction of Cervical Ripening: A Randomized Placebo-Controlled Trial.

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Ramya Krishnamurthy

2015-06-01

Full Text Available To evaluate the safety and efficacy of Isosorbide mononitrate (IMN as a cervical ripening agent prior to induction of labour in term pregnant women.A randomized placebo-controlled study was conducted on 100 term singleton pregnancies planned for induction of labour. The participants were randomly assigned to two groups. One group received 40 mg IMN and the other group received 40mg of placebo kept vaginally. The main outcome of this study was to evaluate the efficacy of IMN in cervical ripening based on the change in modified Bishop score and the effect on time duration between the drug insertion and delivery. Safety of isosorbide mononitrate was assessed by measuring variables related to maternal and neonatal outcomes.Baseline demographic characteristics were similar in both groups. The mean change in modified Bishop score after 2 doses of 40mg IMN was insignificant when compared to placebo. Though IMN shortened the time duration between the drug insertion to delivery when compared to placebo, it was statistically insignificant. The need for oxytocin and 2(nd ripening agent was less in IMN group when compared to placebo group but statistically this also proved to be insignificant. It was noted that there was an increase in caesarean deliveries in IMN than in placebo group. IMN did not cause any significant change in maternal hemodynamics and adverse side effects. Though NICU admission and stay was less in IMN than in placebo group, it was statistically insignificant.Though IMN did not cause any maternal and neonatal adverse effects, it was found to be inefficient in comparison to placebo as a cervical ripening agent.

Validation and acceptability of double-blind, placebo-controlled food challenges in children

NARCIS (Netherlands)

Venter, Carina; Maslin, Kate; Patil, Veeresh; Grundy, Jane; Glasbey, Gillian; Raza, Abid; Vlieg-Boerstra, Berber; Dean, Taraneh

2016-01-01

The Double Blind Placebo Controlled Food Challenge (DBPCFC) is considered the gold standard for food allergy diagnosis (1, 2). It is recommended that active and placebo challenge foods for DBPCFCs are sufficiently blinded in terms of smell, flavour and texture. Difficulties arise with children

Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

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Dezzutti Charlene

2011-03-01

Full Text Available Abstract Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic. Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.

Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model

OpenAIRE

Luca Puviani; Sidita Rama

2016-01-01

Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of th...

Randomized clinical trial comparing oral prednisone (50 mg) with placebo before laparoscopic cholecystectomy

DEFF Research Database (Denmark)

Bisgaard, Thue; Schulze, S.; Hjortso, N.C.

2008-01-01

cholecystectomy. Methods In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain......-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). Conclusion There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy Udgivelsesdato: 2008/2...

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

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Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological

Intervenciones Placebo Para Incrementar el Rendimiento Deportivo: un Tema Revisitado

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MILDRETH LARQUIN-CASTILLO

2015-01-01

Full Text Available Las intervenciones psicológicas para incrementar el rendimiento de los deportistas han ganado gran popularidad. En este artículo se realizó una revisión de la utilización de intervenciones placebo para potenciar el rendimiento deportivo, a partir de la cual se concluyó que el contexto de aplicación, los rasgos de personalidad del deportista y el ritual de intervención han sido propuestos como los factores más relevantes a tomar en consideración. Se estima que, a pesar de las limitaciones, las intervenciones placebo constituyen alternativas eficaces que tienen distintos modos de aplicación. La utilización de vías conscientes y no-conscientes para activar el efecto placebo se materializa en el empleo de las potencialidades que brindan tanto la sugestión verbal como el priming.

Placebo effect in clinical trial design for irritable bowel syndrome.

Science.gov (United States)

Shah, Eric; Pimentel, Mark

2014-04-30

Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various ap-proaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.

New validated recipes for double-blind placebo-controlled low-dose food challenges.

Science.gov (United States)

Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

2013-05-01

Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Vortioxetine versus placebo in major depressive disorder comorbid with social anxiety disorder.

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Liebowitz, Michael R; Careri, Jason; Blatt, Kyra; Draine, Ann; Morita, Junko; Moran, Melissa; Hanover, Rita

2017-12-01

Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD) are highly comorbid, yet the combined condition has not been subject to any placebo-controlled treatment trials. This study reports a trial of vortioxetine, an antidepressant that has also shown benefit in Generalized Anxiety Disorder (GAD), in patients meeting DSM-5 criteria for both MDD and SAD. The study was a 12-week double-blind, placebo-controlled comparison of vortioxetine 10-20 mg/day or placebo administered on a 1:1 ratio. The study was designed to include 40 male or female outpatients aged 18-70 years. The primary endpoint was the "composite" Clinical Global Impression of Improvement (CGI-I) responder rate, factoring in improvement in both MDD and SAD features. Major secondary outcome measures were changes on the Montgomery Asberg Depression Rating Scale (MADRS) and Liebowitz Social Anxiety Scale (LSAS). On the composite CGI-I, 10 of 20 (50%) vortioxetine and six of 20 (30%) placebo-treated patients were rated as responders, a non-significant difference. However, vortioxetine-treated patients did show significantly greater improvement than those on placebo on both the MADRS (effect size 0.672) and LSAS (effect size 0.714). Efficacy in depression was seen before improvement in SAD. Adverse effects were similar to those previously reported. In this preliminary trial vortioxetine appears safe and effective for patients with MDD comorbid with SAD, with robust effect sizes on dimensional measures of both depression and social anxiety, but failure to separate from placebo on the primary outcome measure of composite responder rate. More studies of patients with comorbid conditions are needed, as this mirrors what is often seen in clinical practice. © 2017 Wiley Periodicals, Inc.

Immunomodulatory effects of ResistAid™: A randomized, double-blind, placebo-controlled, multidose study.

Science.gov (United States)

Udani, Jay K

2013-01-01

To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18-61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine).

Informing Patients About Placebo Effects: Using Evidence, Theory, and Qualitative Methods to Develop a New Website.

Science.gov (United States)

Greville-Harris, Maddy; Bostock, Jennifer; Din, Amy; Graham, Cynthia A; Lewith, George; Liossi, Christina; O'Riordan, Tim; White, Peter; Yardley, Lucy; Bishop, Felicity L

2016-06-10

According to established ethical principles and guidelines, patients in clinical trials should be fully informed about the interventions they might receive. However, information about placebo-controlled clinical trials typically focuses on the new intervention being tested and provides limited and at times misleading information about placebos. We aimed to create an informative, scientifically accurate, and engaging website that could be used to improve understanding of placebo effects among patients who might be considering taking part in a placebo-controlled clinical trial. Our approach drew on evidence-, theory-, and person-based intervention development. We used existing evidence and theory about placebo effects to develop content that was scientifically accurate. We used existing evidence and theory of health behavior to ensure our content would be communicated persuasively, to an audience who might currently be ignorant or misinformed about placebo effects. A qualitative 'think aloud' study was conducted in which 10 participants viewed prototypes of the website and spoke their thoughts out loud in the presence of a researcher. The website provides information about 10 key topics and uses text, evidence summaries, quizzes, audio clips of patients' stories, and a short film to convey key messages. Comments from participants in the think aloud study highlighted occasional misunderstandings and off-putting/confusing features. These were addressed by modifying elements of content, style, and navigation to improve participants' experiences of using the website. We have developed an evidence-based website that incorporates theory-based techniques to inform members of the public about placebos and placebo effects. Qualitative research ensured our website was engaging and convincing for our target audience who might not perceive a need to learn about placebo effects. Before using the website in clinical trials, it is necessary to test its effects on key outcomes

Patient attitudes about the clinical use of placebo: qualitative perspectives from a telephone survey.

Science.gov (United States)

Ortiz, Robin; Chandros Hull, Sara; Colloca, Luana

2016-04-04

To examine qualitative responses regarding the use of placebo treatments in medical care in a sample of US patients.Survey studies suggest a deliberate clinical use of placebos by physicians, and prior research has found that although most US patients find placebo use acceptable, the rationale for these beliefs is largely unknown. Members of the Outpatient Clinic at the Kaiser Permanente Northern California interviewed research participants who had been seen for a chronic health problem at least once in the prior 6 months. 853 women (61%) and men, white (58%) and non-white participants aged 18-75 years. Qualitative responses on perceptions of placebo use from one-time telephone surveys were analysed for common themes and associations with demographic variables. Prior results indicated that a majority of respondents felt it acceptable for doctors to recommend placebo treatments. Our study found that a lack of harm (n=291, 46.1%) and potential benefit (n=250, 39.6%) were the most common themes to justify acceptability of placebo use. Responses citing potential benefit were associated with higher education (r=0.787; pright to know and power of the mind. Older age was associated with likelihood to cite overall physician, as opposed to treatment, related themes (r=0.753; prights-and-licensing/

Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study

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Homa Sadeghian

2015-01-01

Full Text Available Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive and preventive (prophylactic treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants, and anti-epileptic drugs (valproate, gabapentin, etc. Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27, valproate 500 mg/d (n = 32 or placebo (n = 26. The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0% patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6% for valproate group and 4 (15.4% for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate.

Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Christensen, Jakob; Petrenaite, Vaiva; Attermann, Jørn

2007-01-01

and taking combination-type oral contraceptives, were randomized to treatment with placebo or a standard combination-type contraceptive pill. The dose-corrected trough plasma concentration of LTG and the ratio of N-2-glucuronide/unchanged LTG on urine after 21 days of concomitant placebo treatment...... was analyzed versus those after 21 days of concomitant treatment with the oral contraceptive pill. RESULTS: The mean dose-corrected LTG concentration after placebo treatment was 84%[95% confidence interval (CI), 45-134%] higher than after oral contraceptives, signifying an almost doubling of the concentration...

"Live high-train low" using normobaric hypoxia: a double-blinded, placebo-controlled study

DEFF Research Database (Denmark)

Siebenmann, Christoph; Robach, Paul; Jacobs, Robert A

2012-01-01

The combination of living at altitude and training near sea level [live high-train low (LHTL)] may improve performance of endurance athletes. However, to date, no study can rule out a potential placebo effect as at least part of the explanation, especially for performance measures. With the use o...... of a placebo-controlled, double-blinded design, we tested the hypothesis that LHTL-related improvements in endurance performance are mediated through physiological mechanisms and not through a placebo effect. Sixteen endurance cyclists trained for 8 wk at low altitude (...

Modeling and simulation of placebo response and dropout patterns in treatment of schizophrenia

NARCIS (Netherlands)

Pilla Reddy, Venkatesh; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; de Greef, Rik; Liu, Jing; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

2010-01-01

Objectives: Unpredictable variation in placebo response within and among clinical trials can substantially affect conclusions about the efficacy of new antipsychotic medications. Developing a robust placebo model accounting for factors like dropouts, disease progression and trial design is crucial

Is TENS purely a placebo effect? A controlled study on chronic low back pain.

Science.gov (United States)

Marchand, S; Charest, J; Li, J; Chenard, J R; Lavignolle, B; Laurencelle, L

1993-07-01

Although high-frequency low-intensity transcutaneous electric nerve stimulation (TENS) has been extensively used to relieve low back pain, experimental studies of its effectiveness have yielded contradictory findings mainly due to methodological problems in pain evaluation and placebo control. In the present study, separate visual analog scales (VAS) were used to measure the sensory-discriminative and motivational-affective components of low back pain. Forty-two subjects were randomly assigned to 1 of 3 groups: TENS, placebo-TENS, and no treatment (control). In order to measure the short-term effect of TENS, VAS pain ratings were taken before and after each treatment session. Also, to measure long-term effects, patients rated their pain at home every 2 h throughout a 3-day period before and 1 week, 3 months and 6 months after the treatment sessions. In comparing the pain evaluations made immediately before and after each treatment session, TENS and placebo-TENS significantly reduced both the intensity and unpleasantness of chronic low back pain. TENS was significantly more efficient than placebo-TENS in reducing pain intensity but not pain unpleasantness. TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness. This additive effect was not found for placebo-TENS. When evaluated at home, pain intensity was significantly reduced more by TENS than placebo-TENS 1 week after the end of treatment, but not 3 months and 6 months later. At home evaluation of pain unpleasantness in the TENS group was never different from the placebo-TENS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

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Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

2014-01-01

Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

["Placebo effect", from personal convictions to collective representations: A psychosocial reading of a pharmacodynamic phenomenon].

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Balez, R; Couturaud, F; Touffet, L

2015-11-01

After starting with a brief historical account of the placebo effect organized around the elaboration of clinical trials and around sham therapy as a method, we will offer a psychosocial point of view on the placebo phenomenon. The placebo effect is at the heart of medicine and particularly of therapeutic trials from theoretical research on a drug to its acceptance and its use in every-day clinical practice. The placebo effect intermingles biology, relationships and the context of therapeutic interactions. This type of phenomenon originates as much from biology as from human psychology. Our article puts more precisely into question the part that psychology has in the placebo phenomenon and suggests a chart to address it. This chart refers both to the pharmacodynamic effect given to drugs in a subjective way, and to the collective representations and social interactions depending on them. What can we say about the psychosociological dimensions of the placebo effect? How is it possible to organize the scope of these dimensions to base systematic studies on them in the field of clinical trials? We try to give elements of response to these questions by suggesting the study of the placebo effect as an original field of study by necessarily mobilizing both health sciences and the human and social sciences. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Induction of nocebo and placebo effects on itch and pain by verbal suggestions

NARCIS (Netherlands)

Laarhoven, A.I.M. van; Vogelaar, M.L.; Wilder-Smith, O.H.G.; Riel, P.L.C.M. van; Kerkhof, P.C.M. van de; Kraaimaat, F.W.; Evers, A.W.M.

2011-01-01

Physical complaints, such as pain, can be effectively reduced by placebo effects through induction of positive expectations, or increased by nocebo effects through induction of negative expectations. In the present study, verbally induced nocebo and placebo effects on itch were experimentally

Evaluation of flurazepam and placebo on sleep disorders in childhood

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Rubens Reimão

1982-03-01

Full Text Available The clinically observed results in 40 patients, from 1 to 15 years old, presenting sleep disturbances, in a comparative and statistically approached study of flurazepam 15mg daily against placebo, are reported. Placebo was administered, followed by the drug, during 14 days each. The chief complaints were sleepwalking, sleep-talking, sleep terror, sleep-related bruxism, sleep-related headbanging, insomnia and excessive movements during sleep. A significant effect of flurazepam on sleepwalking, sleep-talking, bruxism, sleep terror and excessive movement during sleep, was observed. The insomniac and headbanging patients were not enough for statistical analysis. Flurazepam side effects were excessive drowsiness during daytime in 3 cases; irritability, 3 cases; nausea and vomiting, 2 cases, and were not correlated with age. Placebo side effects were similar, except for nausea and vomiting which were not observed. It was necessary to discontinue flurazepam in 2 cases, because of excessive drowsiness during daytime, which did not improve when reducing the dose.

Caffeine counteracts impairments in task-oriented psychomotor performance induced by chlorpheniramine: a double-blind placebo-controlled crossover study.

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Kim, Sung-Wan; Bae, Kyung-Yeol; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Kim, Jong-Keun; Kang, Gaeun; Yoon, Jin-Sang

2013-01-01

This study aimed to evaluate the effects of chlorpheniramine on psychomotor performance and the counteracting effects of caffeine on those sedative antihistamine actions. Sixteen healthy young men participated in this study. Using a double-blind placebo-controlled crossover design, each subject was administered one of the following conditions in a random order with a one-week interval: 'placebo-placebo', '4 mg of chlorpheniramine-placebo', 'placebo-200 mg of caffeine' or '4 mg of chlorpheniramine-200 mg of caffeine'. Before and after the treatments, psychomotor functions were assessed using a battery of tests. Additionally, subjective responses were assessed using a visual analogue scale (VAS). Psychomotor performance changed over time in different ways according to the combination of study medications. In the 'chlorpheniramine-placebo' condition, reaction times of the compensatory tracking task were significantly impaired compared with the other three conditions. In addition, the number of omission errors of the continuous performance test were significantly greater compared with the 'placebo-caffeine' condition. However, the response pattern of the 'chlorpheniramine-caffeine' condition was not significantly different from that of the 'placebo-placebo' condition. Changes of VAS for sleepiness were significantly greater in the 'chlorpheniramine-placebo' condition compared with the other three conditions. In conclusion, chlorpheniramine significantly increases subjective sleepiness and objectively impairs psychomotor performance. However, caffeine counteracts these sedative effects and psychomotor impairments.

Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

DEFF Research Database (Denmark)

Juul, Rasmus V; Foster, David J R; Upton, Richard N

2014-01-01

The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine...... in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed......, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described....

Placebo effect of an inert gel on experimentally induced leg muscle pain

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James G Hopker

2010-11-01

Full Text Available James G Hopker1, Abigail J Foad2, Christopher J Beedie2, Damian A Coleman2, Geoffrey Leach11Centre for Sports Studies, University of Kent, Chatham, Kent, UK; 2Department of Sports Science, Tourism and Leisure, Canterbury Christ Church University, Canterbury, Kent, UKPurpose: This study examined the therapeutic effects of an inert placebo gel on experimentally induced muscle pain in a sports therapy setting. It aimed to investigate the degree to which conditioned analgesia, coupled with an expectation of intervention, was a factor in subsequent analgesia.Methods: Participants were sixteen male and eight female sports therapy students at a UK University. With institutional ethics board approval and following informed consent procedures, each was exposed to pain stimulus in the lower leg in five conditions, ie, conditioning, prebaseline, experimental (two placebo gel applications, and postbaseline. In conditioning trials, participants identified a level of pain stimulus equivalent to a perceived pain rating of 6/10. An inert placebo gel was then applied to the site with the explicit instruction that it was an analgesic. Participants were re-exposed to the pain stimulus, the level of which, without their knowledge, had been decreased, creating the impression of an analgesic effect resulting from the gel. In experimental conditions, the placebo gel was applied and the level of pain stimulus required to elicit a pain rating of 6/10 recorded.Results: Following application of the placebo gel, the level of pain stimulus required to elicit a pain rating of 6/10 increased by 8.2%. Application of the placebo gel significantly decreased participant’s perceptions of muscle pain (P = 0.001.Conclusion: Subjects’ experience and expectation of pain reduction may be major factors in the therapeutic process. These factors should be considered in the sports therapeutic environment.Keywords: conditioning, expectation, perception, positive belief, sports therapy

Lycopene in the management of oral lichen planus: A placebo-controlled study

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Nisheeth Saawarn

2011-01-01

Settings and Design: This prospective, randomized, double-blind, placebo-controlled study was done in the Oral Medicine Department of a postgraduate teaching dental hospital in India. Materials and Methods: Thirty symptomatic OLP patients, randomly divided into two groups of 15 each, were administered lycopene 8 mg/day and an identical placebo, respectively, for 8 consecutive weeks. Burning sensation using visual analogue scale and overall treatment response using Tel Aviv-San Francisco scale were recorded at every visit. The data obtained were analyzed statistically using Wilcoxon Rank test, Mann-Whitney and Fischer′s Exact test. Results: A higher (84% reduction in burning sensation was seen in lycopene than in the placebo group (67%. All 15 (100% patients in the lycopene group showed 50% or more benefit and 11 (73.3% patients showed 70-100% benefit, while this number was only 10 and 4 (26.7%, respectively, in the placebo group. Conclusion: Lycopene was very effective in the management of OLP, and oxidative stress may have a role in disease pathogenesis.

Quantifying the placebo effect in psychological outcomes of exercise training: a meta-analysis of randomized trials.

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Lindheimer, Jacob B; O'Connor, Patrick J; Dishman, Rod K

2015-05-01

The placebo effect could account for some or all of the psychological benefits attributed to exercise training. The magnitude of the placebo effect in psychological outcomes of randomized controlled exercise training trials has not been quantified. The aim of this investigation was to estimate the magnitude of the population placebo effect in psychological outcomes from placebo conditions used in exercise training studies and compare it to the observed effect of exercise training. Articles published before 1 July 2013 were located using Google Scholar, MEDLINE, PsycINFO, and The Cochrane Library. To be included in the analysis, studies were required to have (1) a design that randomly assigned participants to exercise training, placebo, and control conditions and (2) an assessment of a subjective (i.e., anxiety, depression, energy, fatigue) or an objective (i.e., cognitive) psychological outcome. Meta-analytic and multi-level modeling techniques were used to analyze effects from nine studies involving 661 participants. Hedges' d effect sizes were calculated, and random effects models were used to estimate the overall magnitude of the placebo and exercise training effects. After adjusting for nesting effects, the placebo mean effect size was 0.20 (95% confidence interval [CI] -0.02, 0.41) and the observed effect of exercise training was 0.37 (95% CI 0.11, 0.63). A small body of research suggests both that (1) the placebo effect is approximately half of the observed psychological benefits of exercise training and (2) there is an urgent need for creative research specifically aimed at better understanding the role of the placebo effect in the mental health consequences of exercise training.

Double blind, placebo-controlled trial of Tranexamic acid on recent internal hemorrhoid bleeding

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Abdul A. Rani

2002-12-01

Full Text Available Double blind randomized placebo controlled trial was conducted to evaluate the efficacy of Tranexamic acid in 54 patients with recent hemorrhoid bleeding. Age, gender, body weight, height, grade of hemorrhoid, time of onset of recent bleeding were comparable between two groups. Analysis of haemostatic effect or stop bleeding as an immediate outcome of this study revealed that in the grade 2 patients, 23/23 (100% of tranexamic group and 18/23(78.26% of placebo group the bleeding stop. After 3 days of observation, there was statistically significant different for the rate of stop bleeding as well as at the end of observation. Bleeding stop earlier in the Tranexamic group with median 4 days (3-5 days, compare to placebo, median 11(9.55-12.45. Analysis of recurrent bleeding as an outcome of this study revealed that in the placebo group 9/18(50% of grade 2 patients and all grade 3 (100%patients suffered from recurrent bleeding. Since the days 4, both group have significant different time for recurrent bleeding and at the end of observation, cumulative probability of free of bleeding between two groups significantly different. Median still stop bleeding in the placebo group was 36 days, and the tranexamic group never reaches the median until the end of observation. Conclusion: tranexamic acid was an effective drug to stop recent hemorrhoid bleeding and prevent further recurrent bleeding, significantly better than placebo. (Med J Indones 2002;11: 215-21Keywords: Tranexamic acid, hemorrhoid bleeding, haemostatic effect, recurrent bleeding.

Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

NARCIS (Netherlands)

Wieringen, S. van; Jansen, T.; Smits, M.G.; Nagtegaal, J.E.; Coenen, A.M.L.

2001-01-01

Objective: To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the

Characteristics of Placebo Responders in Pediatric Clinical Trials of Attention-Deficit/Hyperactivity Disorder

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Newcorn, Jeffrey H.; Sutton, Virginia K.; Zhang, Shuyu; Wilens, Timothy; Kratochvil, Christopher; Emslie, Graham J.; D'Souza, Deborah N.; Schuh, Leslie M.; Allen, Albert J.

2009-01-01

Objective: Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo…

Trick or treat: The effect of placebo on the power of pharmacogenetic association studies

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Singer Clara

2005-03-01

Full Text Available Abstract The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drugtreated patients. We show that: (i the placebo 'response' strongly affects the statistical power of association studies -- even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii power is dramatically increased when adding markers; (iv an optimal study design includes a similar number of placebo- and drugtreated patients; and (v in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.

Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus.

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Syngelaki, Argyro; Nicolaides, Kypros H; Balani, Jyoti; Hyer, Steve; Akolekar, Ranjit; Kotecha, Reena; Pastides, Alice; Shehata, Hassan

2016-02-04

Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin. In this double-blind, placebo-controlled trial, we randomly assigned pregnant women without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35 to receive metformin, at a dose of 3.0 g per day, or placebo (225 women in each group) from 12 to 18 weeks of gestation until delivery. The BMI was calculated at the time of study entry (12 to 18 weeks of gestation). The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD (equivalent to a 50% reduction, from 20% to 10%, in the incidence of large-for-gestational-age neonates). Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia, as well as the incidence of adverse neonatal outcomes. Randomization was performed with the use of computer-generated random numbers. The analysis was performed according to the intention-to-treat principle. A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], Pmetformin group than in the placebo group. There were no significant between-group differences in the incidence of gestational diabetes, large

Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial.

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Li, Jin; Qin, Shukui; Xu, Ruihua; Yau, Thomas C C; Ma, Brigette; Pan, Hongming; Xu, Jianming; Bai, Yuxian; Chi, Yihebali; Wang, Liwei; Yeh, Kun-Huei; Bi, Feng; Cheng, Ying; Le, Anh Tuan; Lin, Jen-Kou; Liu, Tianshu; Ma, Dong; Kappeler, Christian; Kalmus, Joachim; Kim, Tae Won

2015-06-01

In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [regorafenib 160 mg once daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3-12·2), overall survival was significantly better with regorafenib

Greater incidence of depression with hypnotic use than with placebo

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Kripke Daniel F

2007-08-01

Full Text Available Abstract Background Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo. Methods The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed. Results Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p Conclusion Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.

Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study.

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Clayton, Anita H; Croft, Harry A; Yuan, James; Brown, Louise; Kissling, Robert

2018-01-01

Depression is often associated with sexual dysfunction, and pharmacologic treatment for hypoactive sexual desire disorder can be considered in women receiving treatment for depression. To evaluate the safety of flibanserin in women treated for depression with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. In this double-blinded, randomized, placebo-controlled trial, women with remitted or mild depression treated with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors who were not postmenopausal and were experiencing symptoms of hypoactive sexual desire disorder (ie, decreased sexual desire and related distress) received flibanserin 50 mg at bedtime (qhs) for 2 weeks and up-titrated to 100 mg qhs, flibanserin 100 mg qhs for the entire treatment period, or placebo for up to 12 weeks. Safety assessment included adverse events and symptoms of depression and anxiety. 73 patients were randomly assigned to flibanserin (both dose groups combined) and 38 to placebo. The sponsor terminated the study early at discontinuation of the development of flibanserin. Treatment duration was at least 8 weeks for 84.9% and 94.7% of patients in the flibanserin and placebo groups, respectively. The most common adverse events (incidence ≥ 2% in the flibanserin group and higher than that in the placebo group) included dry mouth (5.5% for flibanserin vs 2.6% for placebo), insomnia (5.5% vs 2.6%), back pain (4.1% vs 2.6%), and dizziness (4.1% vs 0.0%). There were no serious adverse events and no instances of suicidal ideation or behavior. The proportions of patients with symptom worsening in the flibanserin and placebo groups, respectively, were 6.9% and 21.6% for depression and 1.4% and 2.7% for anxiety. Remission of depression at study end point, as measured by the Quick Inventory of Depressive Symptomatology-Self Report, was experienced by 19.4% of flibanserin-treated patients and 10.8% of patients

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

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Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

2014-01-01

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

A survey of patient preferences for a placebo orodispersible tablet

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Wade AG

2012-03-01

Full Text Available Alan G Wade1, Gordon M Crawford1, David Young21CPS Research, Glasgow, UK; 2Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, UKAim: To assess the attitudes and preferences of patients currently being treated for depression or anxiety disorders with traditional oral antidepressants relative to a placebo orodispersible (ODT formulation of escitalopram.Methods: This was an open study collecting patient-reported outcome data from patients with anxiety or depression that were treated with oral antidepressant medication on Day 0 before and after receiving a single placebo ODT, and on Day 3 or 4 after receiving two further daily doses of placebo ODT. Patients aged 18–80 years who were currently receiving treatment with oral antidepressants were recruited from general practice and by advertising. Patients with significant symptoms of anxiety or depression (scoring ≥9 on either the depression or anxiety subscales of the Hospital Anxiety and Depression Scale were included in the study.Results: A total of 150 patients were enrolled in and completed the study. About 37% of the patients had had trouble with swallowing tablets, and patients with higher depression scores reported more general swallowing problems than those with lower scores (P = 0.002. Most patients (75.3% believed that an ODT might work faster but that it would make no difference to the effectiveness of the medication (63.1% or the number of side effects (81.3%. About 96% of the patients reported experiencing a pleasant taste following the placebo ODT, although seven patients did not like its taste or aftertaste. This study found that 80.7% of patients reported that the tablets were easy or very easy to get out of the packaging.Conclusion: Based on the results of the placebo version of escitalopram ODT, the escitalopram ODT is likely to be well accepted by patients suffering from anxiety or depressive symptoms.Keywords: ODT, swallowing difficulties

Can homeopathically prepared mercury cause symptoms in healthy volunteers? A randomized, double-blind placebo-controlled trial.

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Vickers, A J; van Haselen, R; Heger, M

2001-04-01

To pilot a method for determining whether homeopathically prepared mercury causes more symptoms (a "drug proving") in healthy volunteers than placebo. One hundred and eighteen (118) healthy volunteers ages 18 to 65 were recruited by local advertising. Subjects unfamiliar with homeopathy undertook a 1-week single-blind placebo run-in, a 1-week of double-blind, randomized treatment on either homeopathically prepared mercury 12C or placebo, and a third week of placebo run-out. Each day, symptoms were recorded on a checklist that included both true mercury symptoms and symptoms not expected to be caused by mercury (false symptoms). Additional symptoms were assessed by open reporting. Outcome was assessed by calculating a score for each day as the number of true symptoms minus the number of false symptoms. The mean score during placebo was then subtracted from the mean score for weeks two and three of the trial. Fourteen (14) subjects dropped out during placebo run-in. The remaining 104 completed the trial. Baseline comparability was good. Mean difference score was -0.125 (SD 3.47) for mercury and -0.221 (SD 3.01) for placebo (p > 0.2). No significant differences between groups were found for the number of subjects meeting predefined criteria for a drug-proving reaction. This pilot study failed to find evidence that mercury 12C causes significantly more symptoms in healthy volunteers than placebo. Questionnaires with a limited number of gross symptoms do not seem to be an appropriate methodological technique in drug proving research. If drug-proving phenomena exist, they appear to be rare.

Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled trial.

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de Bejczy, Andrea; Löf, Elin; Walther, Lisa; Guterstam, Joar; Hammarberg, Anders; Asanovska, Gulber; Franck, Johan; Isaksson, Anders; Söderpalm, Bo

2015-11-01

Alcohol dependence is a devastating illness affecting a large population, and new pharmacological treatments with good efficacy are greatly needed. One potential candidate is varenicline, a smoking cessation agent with partial agonist action at α4 β2 nicotinic acetylcholine receptors. A total of 160 subjects, 30 to 70 years of age, fulfilling DSM-IV criteria for alcohol dependence without any serious physical or mental disorders, were recruited through advertisement at 3 university clinics in Sweden during March 2009 to January 2011. After a 2-week placebo run-in period, subjects received 2 mg varenicline daily (titrated from 0.5 mg during first week) or placebo for 12 weeks in a double-blind manner. The primary outcome was the proportion of heavy drinking days, measured by self-reported alcohol consumption. Primary and secondary outcomes were calculated as a mean over the 10-week steady-state active treatment period. In the primary outcome analysis, no effect of varenicline over placebo was found (p = 0.73 for the intention to treat [ITT] and 0.92 for per protocol [PP]). Secondary outcome analysis found a significant reduction of specific alcohol marker phosphatidylethanol (PEth) in the blood in the varenicline group compared to placebo (p = 0.02 ITT). Craving (p = 0.048 PP) and Alcohol Use Disorders Identification Test (AUDIT) scores (p = 0.015 ITT) were also reduced in the active treatment group. PEth more strongly correlated with self-reported alcohol consumption than carbohydrate-deficient ttransferrin and γ-glutamyl transferase, and correlation coefficients were higher in the varenicline group than in the placebo group for all markers. Although the results of the main outcome of this study did not support an effect of varenicline in alcohol-dependent individuals, the secondary analyses of PEth, craving and AUDIT score support an effect of varenicline on alcohol consumption. The disclosure of a treatment effect and the lack of a clear placebo effect when

Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial.

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Park, Susanna B; Vucic, Steve; Cheah, Benjamin C; Lin, Cindy S-Y; Kirby, Adrienne; Mann, Kristy P; Zoing, Margie C; Winhammar, Jennica; Kiernan, Matthew C

2015-12-01

Abnormalities in membrane excitability and Na(+) channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na(+) channel blocker and membrane stabiliser flecainide in ALS. A double-blind, placebo-controlled, randomised clinical trial of flecainide (200 mg/day) for 32-weeks with a 12-week lead-in phase was conducted in participants with probable or definite ALS recruited from multiple Australian centres (ANZCT Registry number ACTRN12608000338369). Patients were reviewed by a cardiologist to rule out cardiac contraindications. Participants were randomly assigned (1:1) to flecainide or placebo using stratified permuted blocks by a central pharmacy. The primary outcome measure was the slope of decline of the ALS Functional Rating Scale-revised (ALS FRS-r) during the treatment period. Between March 11, 2008 and July 1, 2010, 67 patients were screened, 54 of whom were randomly assigned to receive flecainide (26 patients) or placebo (28 patients). Four patients in the flecainide group and three patients in the placebo group withdrew from the study. One patient in the flecainide group died during the study, attributed to disease progression. Flecainide was generally well tolerated, with no serious adverse events reported in either group. There was no significant difference in the rate of decline in the primary outcome measure ALS-FRS-r between placebo and flecainide treated patients (Flecainide 0.65 [95% CI 0.49 to 0.98]; Placebo 0.81 [0.49 to 2.12] P = 0.50). However, the rate of decline of the neurophysiological index was significantly reduced in the flecainide group (Flecainide 0.06 [0.01 to 0.11]; Placebo 0.14 [0.09 to 0.19], P = 0.02). Placebo-treated patients demonstrated greater CMAP amplitude reduction during the course of the study in the subset of patients with a reduced baseline CMAP amplitude (Flecainide: - 15 ± 12%; Placebo - 59 ± 12%; P = 0.03). Flecainide

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

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Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Intermittent or daily montelukast versus placebo for episodic asthma in children.

Science.gov (United States)

Valovirta, Erkka; Boza, Maria L; Robertson, Colin F; Verbruggen, Nadia; Smugar, Steven S; Nelsen, Linda M; Knorr, Barbara A; Reiss, Theodore F; Philip, George; Gurner, Deborah M

2011-06-01

No standard, optimal treatment exists for severe intermittent (ie, episodic) asthma in children. However, evidence suggests that both daily and episode-driven montelukast are effective for this phenotype. To assess the regimen-related efficacy of montelukast in treating pediatric episodic asthma. A multicenter, randomized, double-blind, double-dummy, parallel-group, 52-week study was performed in children 6 months to 5 years of age comparing placebo with two regimens of montelukast 4 mg: (1) daily; or (2) episode-driven for 12 days beginning with signs/symptoms consistent with imminent cold or breathing problem. The main outcome measure was the number of asthma episodes (symptoms requiring treatment) culminating in an asthma attack (symptoms requiring physician visit, emergency room visit, corticosteroids, or hospitalization). Five hundred eighty-nine patients were randomized to daily montelukast, 591 to intermittent montelukast, and 591 to placebo. Compared with placebo, no significant difference was seen between daily montelukast (P = .510) or intermittent montelukast (P = .884) in the number of asthma episodes culminating in an asthma attack over 1 year. Daily montelukast reduced symptoms over the 12-day treatment period of asthma episodes compared with placebo (P = .045). Beta-agonist use was reduced with both daily (P = .048) and intermittent montelukast (P = .028) compared with placebo. However, because of prespecified rules for multiplicity adjustments (requiring a positive primary endpoint), statistical significance for secondary endpoints cannot be concluded. All treatments were well tolerated. Montelukast did not reduce the number of asthma episodes culminating in an asthma attack over 1 year in children 6 months to 5 years of age, although numerical improvements occurred in some endpoints. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effect of aromatherapy massage on menopausal symptoms: a randomized placebo-controlled clinical trial.

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Darsareh, Fatemeh; Taavoni, Simin; Joolaee, Soodabeh; Haghani, Hamid

2012-09-01

Menopause is a significant event in most women's lives because it marks the end of a woman's natural reproductive life. The purpose of this study was to determine the effect of aromatherapy massage on menopausal symptoms. A randomized placebo-controlled clinical trial was conducted at a menopausal clinic at a gynecology hospital in Tehran. The study population comprised 90 women who were assigned to an aromatherapy massage group, a placebo massage group, or a control group. Each participant in the aromatherapy massage group received 30-minute aromatherapy treatment sessions twice a week for 4 weeks with aroma oil, whereas participants in the placebo massage group received the same treatment with plain oil. No treatment was provided to participants in the control group. The outcome measures in this study were menopausal symptoms, as obtained through the Menopause Rating Scale. The mean baseline level of the menopausal score did not differ among all groups. However, after eight sessions of intervention, the Menopause Rating Scale score differed significantly among the three groups (P aromatherapy massage group and the placebo massage group had a lower menopausal score than the control group (P aromatherapy massage and the placebo massage groups were compared, the menopausal score for the aromatherapy massage group was found to be significantly lower (P aromatherapy massage were effective in reducing menopausal symptoms. However, aromatherapy massage was more effective than only massage.

A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain.

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McElroy, Susan L; Winstanley, Erin; Mori, Nicole; Martens, Brian; McCoy, Jessica; Moeller, Dianna; Guerdjikova, Anna I; Keck, Paul E

2012-04-01

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

A virtual experimenter to increase standardization for the investigation of placebo effects

Directory of Open Access Journals (Sweden)

Bjoern Horing

2016-07-01

Full Text Available Abstract Background Placebo effects are mediated by expectancy, which is highly influenced by psychosocial factors of a treatment context. These factors are difficult to standardize. Furthermore, dedicated placebo research often necessitates single-blind deceptive designs where biases are easily introduced. We propose a study protocol employing a virtual experimenter – a computer program designed to deliver treatment and instructions – for the purpose of standardization and reduction of biases when investigating placebo effects. Methods To evaluate the virtual experimenter’s efficacy in inducing placebo effects via expectancy manipulation, we suggest a partially blinded, deceptive design with a baseline/retest pain protocol (hand immersions in hot water bath. Between immersions, participants will receive an (actually inert medication. Instructions pertaining to the medication will be delivered by one of three metaphors: The virtual experimenter, a human experimenter, and an audio/text presentation (predictor “Metaphor”. The second predictor includes falsely informing participants that the medication is an effective pain killer, or correctly informing them that it is, in fact, inert (predictor “Instruction”. Analysis will be performed with hierarchical linear modelling, with a sample size of N = 50. Results from two pilot studies are presented that indicate the viability of the pain protocol (N = 33, and of the virtual experimenter software and placebo manipulation (N = 48. Discussion It will be challenging to establish full comparability between all metaphors used for instruction delivery, and to account for participant differences in acceptance of their virtual interaction partner. Once established, the presence of placebo effects would suggest that the virtual experimenter exhibits sufficient cues to be perceived as a social agent. He could consequently provide a convenient platform to investigate effects of

The antidepressant debate and the balanced placebo trial design: an ethical analysis.

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Waring, Duff R

2008-12-01

There is ongoing debate about whether randomized, placebo-controlled trials under a double-blind have reliably established the pharmacological efficacy of antidepressants. Numerous meta-analyses of antidepressant efficacy trials, e.g., Kirsch et al. [Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. food and drug administration. Prevention and Treatment, 5, Article 23. (Retrieved July 19, 2007 from http://journals.apa.org/prevention/volume5)], have shown a modest drug-placebo difference but methodological problems with standard trial design preclude a definitive conclusion that this difference results from specific biological effects of antidepressants or the nonspecific factors that have not been adequately excluded. Standard trial design assumes the additivity thesis of pharmacological efficacy, being the assumption that the specific or "true" magnitude of the pharmacological effect is limited to the difference between the drug and placebo responses in a standard trial. If the drug effects are as small as these meta-analyses suggest, then their clinical effectiveness is questionable. If the drug effects are actually larger but masked by placebo effects, then the additivity thesis is not valid and we risk false negative results with standard trial design. Kirsch et al. propose an alternative, four arm balanced placebo trial design (BPTD) that can accurately test the additivity thesis. The BPTD uses antidepressants, active placebos and the intentional deception of research subjects. My focal question is whether the BPTD is ethically defensible. I will explore two objections that can be raised against it: 1) lying to BPTD research subjects violates their autonomy and exploits their illness and 2) the BPTD may not enable us to test the additivity thesis with accuracy, i.e., it may contribute to the masking of drug effects that it aims to avoid. I argue that these

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

DEFF Research Database (Denmark)

Baandrup, Lone; Lindschou, Jane; Winkel, Per

2016-01-01

OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.

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Sunay, Didem; Sunay, Melih; Aydoğmuş, Yasin; Bağbancı, Sahin; Arslan, Hüseyin; Karabulut, Ayhan; Emir, Levent

2011-05-01

Acupuncture therapy has been used by many researchers in both male and female sexual dysfunction studies. To determine whether acupuncture is effective as a premature ejaculation (PE) treatment compared with paroxetine and placebo. The study was conducted with methodologic rigor based on Consolidated Standards of Reporting Trials (CONSORT) criteria. Ninety patients referred to the urology clinic at a tertiary training and research hospital with PE were included in this randomized controlled trial and randomly assigned into paroxetine, acupuncture, and placebo groups. Heterosexual, sexually active men aged between 28 and 50 yr were included. Men with other sexual disorders, including erectile dysfunction; with chronic psychiatric or systemic diseases; with alcohol or substance abuse; or who used any medications were excluded. The medicated group received paroxetine 20 mg/d; the acupuncture or sham-acupuncture (placebo) groups were treated twice a week for 4 wk. Intravaginal ejaculation latency times (IELTs) and the Premature Ejaculation Diagnostic Tool (PEDT) were used to assess PE. IELTs were calculated by using a partner-held stopwatch. Data were analyzed statistically. Median PEDT scores of paroxetine, acupuncture, and placebo groups were 17.0, 16.0, and 15.5 before treatment, and 10.5, 11.0, and 16.0 after treatment, respectively (p=0.001, p=0.001, and p=0.314, respectively). Subscores after treatment were significantly lower than subscores before treatment in the paroxetine and acupuncture groups but remained the same in the placebo group. Significant differences were found between mean-rank IELTs of the paroxetine and placebo groups (p=0.001) and the acupuncture and placebo groups (p=0.001) after treatment. Increases of IELTs with paroxetine, acupuncture, and placebo acupuncture were 82.7, 65.7, and 33.1 s, respectively. Extent of ejaculation delay induced by paroxetine was significantly higher than that of acupuncture (p=0.001). The most important limitation

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.

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Schellenberg, R

2001-01-20

To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (Pagnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

[Research ethics and the use of placebo: status of the debate in Canada].

Science.gov (United States)

Keating, Bernard

2004-01-01

The question of the use of the placebo is one of the most controversial in the field of the ethics of research today. The use of the placebo remains the standard practice of biomedical research in spite of the fact that various revisions of the Helsinki Declaration have sought to limit its use. In Canada, the Tri-council policy statement: Ethical conduct for research involving humans adopted a very restrictive position with respect to the use of placebos, precisely defining the situations in which its use would meet the demands of ethical research. The positions taken by the various ethical decision-making bodies are, however, hardly shared by regulatory bodies such as the Food and drug administration (FDA), the Council for international organization of medical sciences (CIOMS) or the European agency for the evaluation of medicinal products (EMEA). This divergence of opinions reveals two quite different conceptions of what constitutes the ethical. In the case of decision-making bodies in the ethical field, it is clearly medicine's Hippocratic Oath which explains their reluctance to use placebos. The first responsibility of the doctor is to "do no harm" to his or her patient. This duty is inherent to the medical profession and as such is not grounded in the view of medicine as a contract for care. In the case of regulatory bodies, it is the vision of "medicine as contract" which is in view; and it is this notion that justifies the use of placebos once free and informed consent has been obtained. It is also worth noting that these regulatory bodies make frequent use of arguments based on utilitarian ends. In an unprecedented move, the World medical association published in October 2001 a clarification note about the use of placebos. An analysis of this text raises the question about its real meaning: clarification or concession?

Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma.

Science.gov (United States)

Wong, Eliza L Y; Sung, Rita Yn Tz; Leung, Ting Fan; Wong, Yeuk Oi; Li, Albert M C; Cheung, Kam Lau; Wong, Chun Kwok; Fok, Tai Fai; Leung, Ping Chung

2009-10-01

The purpose of this trial was to evaluate whether the herbal formula of CUF2 used as complementary therapy improves the clinical symptoms and biochemical markers in children with asthma using inhaled corticosteroids. In a double-blind, placebo-controlled prospective trial, 85 children with asthma aged 7-15 years were randomly assigned to receive either a daily oral herbal formula of 0.619-g CUF2 capsule of dried aqueous extract with an equal weight of five herbs (Astragalus mongholius Bunge, Cordyceps sinensis Sacc., Radix stemonae, Bulbus fritillariae cirrhosae, and Radix scutellariae) or placebo for 6 months. The primary endpoint was the change in steroids dosage; the secondary outcomes included the disease severity score, lung function test, and biochemical markers in blood. Eighty-five (85) children (42 on active treatment and 43 on placebo) completed the 6-month clinical trial. Children randomized to the herbal formula of CUF2 and the placebo showed a similar improvement in clinical symptoms and biomedical markers. The comparison between the CUF2 group and the placebo group showed no significant difference on the dosage of steroids (-2.3 versus -3.1 mg, p = 0.915), disease severity score (-2.3 versus -3.1, p = 0.215), and lung function test of forced expiratory volume in 1 second/forced vital capacity percent (0.1 versus 0.6%, p = 0.809) and peak expiratory flow rate (-7.3 versus -0.6 l/minutes, p = 0.118). No significant difference was found between the two study groups in the biochemical outcomes measured. The intervention effect of CUF2 was smaller than the placebo effect. This study provides no evidence to support the use of the herbal formula of CUF2 in children with asthma. Parents are thus advised to discuss with health professionals before choosing an herbal formula in preference to conventional treatment modes.

Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial.

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Furyk, Jeremy S; Chu, Kevin; Banks, Colin; Greenslade, Jaimi; Keijzers, Gerben; Thom, Ogilvie; Torpie, Tom; Dux, Carl; Narula, Rajan

2016-01-01

We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter. This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion. There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups. We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

State-dependent memory effects using caffeine and placebo do not extend to metamemory.

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Kelemen, William L; Creeley, Catherine E

2003-01-01

The authors examined the impact of caffeine on human memory and predictions of memory (i.e., metamemory). On Day 1, 83 college students drank a sweetened beverage containing either caffeine (4 mg/kg body weight) or a placebo before they studied 40 pairs of words. While the participants studied, they predicted their future memory performance for each word pair. On Day 2, the participants again received caffeine or a placebo before the memory test. The participants who drank the same beverage on both days (either caffeine or a placebo) recalled more word pairs than did those who drank different beverages (caffeine on 1 day and a placebo on the other day). In contrast, memory predictions were more accurate when the beverages did not match on both days. These data provide evidence for state-dependent memory when caffeine is used, but not for state-dependent metamemory. People's memory and their predictions of memory can be influenced in different ways if they drink caffeine before they study or take a test.

Placebo response in binge eating disorder: a pooled analysis of 10 clinical trials from one research group.

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Blom, Thomas J; Mingione, Carolyn J; Guerdjikova, Anna I; Keck, Paul E; Welge, Jeffrey A; McElroy, Susan L

2014-03-01

The aim of this study was to gain further understanding of placebo response in binge eating disorder. We pooled participant-level data from 10 double-blind, placebo-controlled, randomized trials of medications for binge eating disorder. The primary outcomes were response (75% reduction in binge eating episodes), cessation of binge eating episodes, change in mean weekly binge eating episodes and binge eating episodes per week. Of 234 participants receiving placebo, 89 (38%) were responders and 59 (26%) attained cessation. Placebo-treated participants significantly reduced their binge eating. The mean (SD) binge eating episodes per week at baseline was 5.2 (3.2) and at endpoint was 2.2 (2.6). Lower baseline binge eating episode frequency and longer study participation were significantly associated with response and cessation. Less severe eating pathology at baseline was associated with higher placebo response and cessation rates. Future clinical trials may want to stipulate that participants exceed a threshold of illness severity, which may lead to better placebo and drug separation. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

Directory of Open Access Journals (Sweden)

Matthias Huber

Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

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Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that

Sodium valproate in the treatment of aggressive behavior in patients with dementia--a randomized placebo controlled clinical trial

NARCIS (Netherlands)

Sival, Rob C.; Haffmans, P. M. Judith; Jansen, Paul A. F.; Duursma, Sijmen A.; Eikelenboom, Piet

2002-01-01

OBJECTIVES: The efficacy and tolerability of sodium valproate 2 x 240 mg compared to placebo were investigated in aggressive behavior in dementia. DESIGN: A randomized, placebo controlled, double-blind cross-over design. The trial included a baseline period (one week); a placebo period (three

Predictive factors for the placebo effect in clinical trials for dry eye: a pooled analysis of three clinical trials.

Science.gov (United States)

Imanaka, Takahiro; Sato, Izumi; Tanaka, Shiro; Kawakami, Koji

2017-11-01

Placebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the placebo response in clinical trials for dry eye. In this study, we investigated the predictive factors for the placebo effect in dry eye clinical trials. A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled randomised clinical trials were analysed by simple and multivariable regression analysis. The corneal fluorescein (FL) staining score and dry eye symptoms were studied at week 4. The variables of interest included gender, age, complications of Sjögren's syndrome, Schirmer's test I value, tear break-up time and conjunctival hyperaemia score. We also conducted a stratified analysis according to the patients' age. Among all the studied endpoints, the baseline scores were significantly related to the corresponding placebo response. In addition, for the FL score and the dryness score, age was a significant predictor of the placebo response (p=0.04 and p<0.0001, respectively). Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores. The baseline scores and age were predictive factors of the placebo response in frequently used endpoints, such as FL score or dryness symptoms. These patient characteristics can be controlled by study design, and our findings enable the design of more efficient placebo-controlled studies with good statistical power. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Reiki Is Better Than Placebo and Has Broad Potential as a Complementary Health Therapy

Science.gov (United States)

2017-01-01

This study reviews the available clinical studies of Reiki to determine whether there is evidence for Reiki providing more than just a placebo effect. The available English-language literature of Reiki was reviewed, specifically for peer-reviewed clinical studies with more than 20 participants in the Reiki treatment arm, controlling for a placebo effect. Of the 13 suitable studies, 8 demonstrated Reiki being more effective than placebo, 4 found no difference but had questionable statistical resolving power, and only one provided clear evidence for not providing benefit. Viewed collectively, these studies provide reasonably strong support for Reiki being more effective than placebo. From the information currently available, Reiki is a safe and gentle “complementary” therapy that activates the parasympathetic nervous system to heal body and mind. It has potential for broader use in management of chronic health conditions, and possibly in postoperative recovery. Research is needed to optimize the delivery of Reiki. PMID:28874060

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

Science.gov (United States)

Sahlsten, Hanna; Virtanen, Juuso; Joutsa, Juho; Niinivirta-Joutsa, Katri; Löyttyniemi, Eliisa; Johansson, Reijo; Paavola, Janika; Taiminen, Tero; Sjösten, Noora; Salonen, Jaakko; Holm, Anu; Rauhala, Esa; Jääskeläinen, Satu K

2017-09-01

Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). Thirty-nine patients (mean age 50.3 years). The mean tinnitus intensity (F 3  = 15.7, p tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

The effect of melatonin on sleep quality after laparoscopic cholecystectomy: a randomized, placebo-controlled trial

DEFF Research Database (Denmark)

Gögenur, Ismail; Kücükakin, Bülent; Bisgaard, Thue

2009-01-01

= 60) or placebo (n = 61) for 3 nights after surgery. Subjective sleep quality, sleep duration, sleep timing, and subjective discomfort (fatigue, general well-being, and pain) were measured. RESULTS: Sleep latency was significantly reduced in the melatonin group (mean [sd] 14 min [18]) compared...... with placebo (28 min [41]) on the first postoperative night (P = 0.015). The rest of the measured outcome variables did not differ between groups. CONCLUSIONS: Melatonin did not improve subjective sleep quality or discomfort compared with placebo after laparoscopic cholecystectomy....

Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

Science.gov (United States)

Elberling, J; Duus Johansen, J; Dirksen, A; Mosbech, H

2006-08-01

Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics Revisão da eficácia do placebo nos ensaios clínicos que comparam antipsicóticos típicos e atípicos

Directory of Open Access Journals (Sweden)

Irismar Reis de Oliveira

2009-03-01

Full Text Available OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.OBJETIVO: Revisar a eficácia do placebo em comparação com a dos antipsicóticos atípicos e típicos no tratamento da esquizofrenia e do transtorno

Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

Directory of Open Access Journals (Sweden)

Bouwense SA

2015-07-01

Full Text Available Stefan AW Bouwense,1 Søren S Olesen,2 Asbjørn M Drewes,2 Harry van Goor,1 Oliver HG Wilder-Smith31Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands; 2Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 3Pain and Nociception Neuroscience Research Group, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud university medical center, Nijmegen, The NetherlandsBackground: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders to placebo or pregabalin treatment. Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15 or placebo (n=12; n=17 treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT in dermatomes C5 (generalized effects and Ventral T10 (segmental effects. Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM paradigm. Results: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA vs placebo responders (−0.1 mA; P=0.015. This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9% vs placebo responders (−17%; P<0.001. CPM changed significantly vs baseline only for pregabalin responders (P=0.006. Conclusion: This hypothesis

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study.

Science.gov (United States)

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas

Buprenorphine Implants for Treatment of Opioid Dependence: Randomized Comparison to Placebo and Sublingual Buprenorphine/Naloxone

Science.gov (United States)

Rosenthal, Richard N.; Ling, Walter; Casadonte, Paul; Vocci, Frank; Bailey, Genie L.; Kampman, Kyle; Patkar, Ashwin; Chavoustie, Steven; Blasey, Christine; Sigmon, Stacey; Beebe, Katherine L.

2015-01-01

Aims To evaluate safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Design Randomized, double-blind, placebo-controlled trial. Subjects received either 4 buprenorphine implants (80 mg/implant) (n=114), 4 placebo implants (n=54), or open-label BNX (12–16 mg/d) (n=119). Setting 20 addiction treatment centers. Participants Adult outpatients (ages 18 to 65) with DSM-IV-TR opioid dependence. Measurements The primary efficacy endpoint was the percent of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). Findings The BI CDF was significantly different from placebo (P<.0001). Mean (95% CI) proportions of urines negative for opioids were: BI: 31.2% (25.3, 37.1) and PI: 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64% vs. 26%, P<.0001), lower clinician-rated (P<.0001) and patient-rated (P<.0001) withdrawal, lower patient-ratings of craving (P<.0001), and better subjects’ (P=.031) and clinicians’ (P=.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P=.0016). Minor implant-site reactions were comparable in the buprenorphine (27.2% [31/114]) and placebo groups (25.9% [14/54]). BI were non-inferior to BNX on percent urines negative for opioids [mean (95% CI): 33.5 (27.3, 39.6); CI for the difference of proportions, (−10.7, 6.2)]. Conclusions Compared with placebo, buprenorphine implants result in significantly less frequent opioid use, and are non-inferior to sublingual buprenorphine/naloxone tablets. PMID:23919595

A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

DEFF Research Database (Denmark)

Vollmer, T L; Sorensen, P S; Selmaj, K

2014-01-01

The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores...... months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly...... reduced with laquinimod [-18 %, risk ratio (RR) = 0.82, 95 % CI 0.66-1.02; p = 0.075] vs. placebo. Laquinimod significantly reduced PBVC (28 %, p change in confirmed disability worsening with laquinimod measured...

Efficacy of atomoxetine in adult attention-Deficit/Hyperactivity Disorder: a drug-placebo response curve analysis

Directory of Open Access Journals (Sweden)

Reimherr Fred

2005-10-01

Full Text Available Abstract Background The objective of this study was to evaluate the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD among adults by using drug-placebo response curve methods. Methods We analyzed data from two double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256 with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomized to 10 weeks of treatment with atomoxetine or placebo, and were assessed with the Conners Adult ADHD Rating Scales and the Clinical Global Impression of ADHD Severity scale before and after treatment. Results Those treated with atomoxetine were more likely to show a reduction in ADHD symptoms than those receiving placebo. Across all measures, the likelihood that an atomoxetine-treated subject improved to a greater extent than a placebo-treated subject was approximately 0.60. Furthermore, atomoxetine prevented worsening of most symptom classes. Conclusion From these findings, we conclude that atomoxetine is an effective treatment for ADHD among adults when evaluated using several criteria.

Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder.

Science.gov (United States)

Soler, Joaquim; Pascual, Juan Carlos; Campins, Josefa; Barrachina, Judith; Puigdemont, Dolors; Alvarez, Enrique; Pérez, Victor

2005-06-01

The aim of this study was to determine the efficacy and safety of dialectical behavior therapy plus olanzapine compared with dialectical behavior therapy plus placebo in patients with borderline personality disorder. Sixty patients with borderline personality disorder were included in a 12-week, double-blind, placebo-controlled study. All patients received dialectical behavior therapy and were randomly assigned to receive either olanzapine or placebo following a 1-month baseline period. Seventy percent of the patients completed the 4-month trial. Combined treatment showed an overall improvement in most symptoms studied in both groups. Olanzapine was associated with a statistically significant improvement over placebo in depression, anxiety, and impulsivity/aggressive behavior. The mean dose of olanzapine was 8.83 mg/day. A combined psychotherapeutic plus pharmacological approach appears to lower dropout rates and constitutes an effective treatment for borderline personality disorder.

Placebo response and remission rates in randomised trials of induction andmaintenance therapy for ulcerative colitis

NARCIS (Netherlands)

Jairath, Vipul; Zou, G. Y.; Parker, Claire E.; Macdonald, John K.; AlAmeel, Turki; Al Beshir, Mohammad; Almadi, Majid A.; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel R.; Koutsoumpas, Andreas; Minas, Elizabeth; Mosli, Mahmoud H.; Samaan, Mark; Khanna, Reena; Travis, Simon; D'Haens, Geert; Sandborn, William J.; Feagan, Brian G.

2017-01-01

Background It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

Science.gov (United States)

Leather, A T; Studd, J W; Watson, N R; Holland, E F

1999-02-01

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Differential Effectiveness of Electromyograph Feedback, Verbal Relaxation Instructions, and Medication Placebo with Tension Headaches

Science.gov (United States)

Cox, Daniel J.; And Others

1975-01-01

Adults with chronic tension headaches were assigned to auditory electromyograph (EMG) feedback (N=9), to progressive relaxation (N=9), and to placebo treatment (N=9). Data indicated that biofeedback and verbal relaxation instructions were equally superior to the medicine placebo on all measured variables in the direction of clinical improvement,…

Tratamento da parada cardíaca experimental com adrenalina, vasopressina ou placebo

Directory of Open Access Journals (Sweden)

Manoel Ângelo Gomes Palácio

2013-12-01

Full Text Available FUNDAMENTO: Na ressuscitação cardiopulmonar (RCP prolongada, o efeito dos vasoconstritores não foi plenamente esclarecido. OBJETIVOS: Avaliar o efeito pressórico da adrenalina e da vasopressina, e observar o retorno da circulação espontânea (RCE. MÉTODOS: Estudo prospectivo, randomizado, cego e placebo-controlado. Após sete minutos em fibrilação ventricular, porcos receberam ciclos de dois minutos de RCP. Tentou-se a desfibrilação (4 J/kg uma vez aos 9 minutos e após cada ciclo, conforme o ritmo verificado, reiniciando-se a RCP imediatamente. Aos 9 minutos e depois de cada cinco minutos, aplicou-se adrenalina 0,02 mg/kg (n = 12 porcos, ou vasopressina 0,4 U/kg (n = 12, ou solução salina 0,9% 0,2 mL/kg (n = 8. A RCP continuou por 30 minutos ou até o RCE. RESULTADOS: A pressão de perfusão coronária aumentou para aproximadamente 20 mmHg nos três grupos. Com os vasoconstritores, a pressão alcançou 35 mmHg versus 15 mmHg com placebo (p < 0,001. Com vasopressina, manteve-se efeito de 15-20 mmHg após três doses versus zero com adrenalina ou placebo. Observou-se o RCE com frequência diferente (p = 0,031 entre adrenalina (10/12, vasopressina (6/12 e placebo (2/8. O tempo médio até o RCE não diferiu (16 minutos, nem o número de doses recebidas até então (uma ou duas. Entre os vasoconstritores não houve diferença significante, mas, frente ao placebo, apenas a adrenalina aumentou significantemente o RCE (p = 0,019. CONCLUSÃO: O efeito pressórico inicial dos vasoconstritores foi equivalente, e a vasopressina manteve um efeito tardio na ressuscitação prolongada. Apesar disso, comparando-se ao placebo, apenas a adrenalina aumentou significantemente a frequência do retorno da circulação espontânea.

Topical sucralfate treatment of anal fistulotomy wounds: a randomized placebo-controlled trial.

Science.gov (United States)

Gupta, Pravin J; Heda, Purushottam S; Shrirao, Subhash A; Kalaskar, Surekha S

2011-06-01

Sucralfate is a cytoprotective agent which adheres to mucoproteins and forms a protective barrier at wound sites. In oral form it is a common ulcer medication, and as a topical preparation it has been used to treat a wide variety of wounds. The present study was designed to evaluate the effectiveness and safety of topical sucralfate in wound healing after anal fistulotomy. Double-blind, randomized controlled study comparing topical application of sucralfate or placebo. Private outpatient clinic specializing in anorectal disease in Nagpur, India. Patients with a wound length of at least 5 cm after low anal fistulotomy were eligible for the study. Patients were randomly assigned to receive ointment containing 7% sucralfate or a placebo ointment consisting of petroleum jelly. Patients were instructed to apply approximately 3 g of ointment to the wound twice daily after a sitz bath for 6 weeks or until the wound had healed. The wounds were examined by a blinded independent observer at 2, 4, and 6 weeks after the operation. The primary end point was the proportion of patients with wounds that had completely healed. Secondary end points included amount of mucosal covering (scored by the observer), adverse events, and postoperative pain (self-rated on a visual analog scale). Of 80 participants (29 women, 51 men; median age, 23 (range, 17-49) years), 76 participants completed the trial (sucralfate, 39; placebo, 37). At 6-week follow-up, complete wound healing was achieved in 37 patients (95%) in the sucralfate group and 27 patients (73%) in the placebo group (P = .009). Mucosal coverage of the wound was significantly greater with sucralfate than with placebo at each measurement point (P = .01). No adverse events were observed. Postoperative pain scores were significantly lower for sucralfate than for placebo at 2 and 4 weeks after the start of treatment. Wound tissue specimens were not available for morphological and ultrastructural analysis. The results of this study add

Placebo cessation in binge eating disorder: effect on anthropometric, cardiovascular, and metabolic variables.

Science.gov (United States)

Blom, Thomas J; Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

2015-01-01

The aim of this study was to evaluate the effects of cessation of binge eating in response to placebo treatment in binge eating disorder (BED) on anthropometric, cardiovascular, and metabolic variables. We pooled participant-level data from 10 randomized, double-blind, placebo-controlled trials of medication for BED. We then compared patients who stopped binge eating with those who did not on changes in weight, body mass index (BMI), systolic and diastolic blood pressure, pulse, and fasting lipids and glucose. Of 234 participants receiving placebo, 60 (26%) attained cessation from binge eating. Patients attaining cessation showed modestly decreased diastolic blood pressure compared with patients who continued to binge eat. Weight and BMI remained stable in patients who stopped binge eating, but increased somewhat in those who continued to binge eat. Patients who stopped binge eating with placebo had greater reductions in diastolic blood pressure and gained less weight than patients who continued to binge eat. Self-report of eating pathology in BED may predict physiologic variables. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Le placebo a-t-il sa place dans la relation soignant–soigné à l’hôpital ?

OpenAIRE

Tacheau , M.; Reny , J.; Crépin , E.; Akhdari , M.; Héron , Anne

2017-01-01

International audience; Some complaints and some diseases lead caregivers to use placebos. What is the caregiver’s intention in this case? Is placebo compatible with the confidence inherent to the relationship between medical team and patient? Could it be considered as a “benevolent lie”? Would it be confusion between placebo and placebo effect? Social and medical representations of care are impregnated with the culture of action. Pharmacological treatment is currently the preponderant respon...

You Can't Always Get What You Want: The Influence of Choice on Nocebo and Placebo Responding.

Science.gov (United States)

Bartley, Hannah; Faasse, Kate; Horne, Rob; Petrie, Keith J

2016-06-01

Choice may be an important influence on the effectiveness and side effects of medical treatments. We investigated the impact of having a choice of medication compared to no choice on both nocebo and placebo responding. Sixty-one participants were randomly assigned to either choose between or be assigned to one of the two equivalent beta-blocker medications (actually placebos) for pre-examination anxiety. There was a greater nocebo response in the no choice group and an increased placebo response in the choice group. Participants in the no choice group attributed significantly more side effects to the tablet than the choice group (p = 0.045), particularly at the 24-h follow-up (p = 0.002). The choice group showed a stronger placebo response in heart rate than the non-choice group. Not being given a choice of medication increased the nocebo effect and reduced the placebo response to the treatment.

Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

Science.gov (United States)

Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

2017-09-08

In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review

DEFF Research Database (Denmark)

Hougaard, Anders; Tfelt-Hansen, Peer

2016-01-01

of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying...... reports of RCTs. RESULTS: A placebo arm was used in requiring more than 75,000 patient days, no difference...... was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine...

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing*

Science.gov (United States)

Antoine, Denis G.; Strain, Eric C.; Tompkins, D. Andrew; Bigelow, George E.

2013-01-01

Background Abuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers. Methods Data were collected from 23 completers of the qualification phase of an abuse liability study. Opioid abusing participants received 30 mg oxycodone and placebo orally on separate days, and were characterized as qualifiers (vs. non-qualifiers) if their peak visual analog scale liking rating for oxycodone was at least 20 points higher than placebo’s peak rating. Groups were compared on demographic characteristics, drug history, and physiologic, subject and observer ratings. Results 61% of participants were qualifiers and 39% were non-qualifiers. Groups had similar demographic characteristics, drug use histories, and pupillary constriction responses. However, unlike qualifiers, non-qualifiers had an exaggerated placebo response for the liking score (p=0.03) and an attenuated oxycodone response for the liking score (p<.0001). Non-qualifiers’ failure to differentiate oxycodone versus placebo was evident for subject and observer ratings. Conclusion Different subjective responses to identical stimuli support the use of a qualification phase in abuse liability assessments. Further research should explore objective measures that may better account for these differences, determine optimal qualification criteria, and explore the developmental course of drug use. This study also documents certain opioid abusers fail to differentiate 30 mg of oxycodone from placebo, a phenomenon deserving further study. PMID:23369645

Placebo HAART Regimen as a Method for Teaching Medication Adherence Issues to Students

OpenAIRE

Sutton, Eliza L; Transue, Emily R; Comes E, Susan; Paauw, Douglas S

2005-01-01

Placebo medication regimens may help educate students about adherence issues. In this randomized trial, 23 third-year medical students took a 2-week placebo regimen mimicking highly active antiretroviral therapy (HAART) during their medicine clerkship; 15 students served as controls. Although no effect was demonstrated from this intervention on an evaluation instrument examining attitudes and beliefs about medication nonadherence, all 23 student-subjects agreed in postintervention interviews ...

Prevalence of lactose intolerance in Chile: a double-blind placebo study.

Science.gov (United States)

Latorre, Gonzalo; Besa, Pablo; Parodi, Carmen G; Ferrer, Verónica; Azocar, Lorena; Quirola, Marife; Villarroel, Luis; Miquel, Juan F; Agosin, Eduardo; Chianale, José

2014-01-01

Lactase non-persistence (LNP), or primary hypolactasia, is a genetic condition that mediates lactose malabsorption and can cause lactose intolerance. Here we report the prevalence of lactose intolerance in a double-blind placebo study. The LCT C>T-13910 variant was genotyped by RT-PCR in 121 volunteers and lactose malabsorption was assessed using the hydrogen breath test (HBT) after consuming 25 g of lactose. Lactose intolerance was assessed by scoring symptoms (SS) using a standardized questionnaire following challenge with a lactose solution or saccharose placebo. The LNP genotype was observed in 57% of the volunteers, among whom 87% were HBT⁺. In the HBT⁺ group the median SS was 9 and in the HBT⁻ group the median SS was 3 (p lactose intolerance was defined as the presence of an SS ≥ 6 points after subtracting the placebo effect and 34% of the study population met this definition. The LNP genotype was present in more than half of subjects evaluated and the observed prevalence of lactose intolerance was 34%. © 2014 S. Karger AG, Basel.

Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.

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André Russowsky Brunoni

Full Text Available BACKGROUND: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs and non-pharmacological (device- rTMS trials. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6 and rTMS studies (0.82; 95%C.I. 0.63 to 1. Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. CONCLUSIONS/SIGNIFICANCE: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies. The magnitude of the placebo response seems to be related with study population and study design rather than the intervention

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial.

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McGraw, Thomas

2016-01-01

To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation. The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or placebo solution for 14 days. The study comprised a screening period (visit 1), endoscopy procedure (visits 2 and 3), and followup telephone calls 30 days post-treatment. Safety end points included adverse events (AEs), clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions. A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment) or visit 3 (after treatment). Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo - nonsignificant difference of -7.5% (95% CI: -21.3, 6.3) between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because of an AE. PEG 3350 ASC is safe and well tolerated in patients with functional constipation (NCT01885104).

Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms.

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Gerber, G S; Kuznetsov, D; Johnson, B C; Burstein, J D

2001-12-01

To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial. The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate. The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73). Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

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Li Li

2010-05-01

Full Text Available Abstract Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p ® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0% subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601

A double-masked, placebo-controlled study of fluoxetine for hypochondriasis.

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Fallon, Brian A; Petkova, Eva; Skritskaya, Natalia; Sanchez-Lacay, Arturo; Schneier, Franklin; Vermes, Donna; Cheng, Jianfeng; Liebowitz, Michael R

2008-12-01

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, +/-23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis.

Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome

DEFF Research Database (Denmark)

Allegretti, Andrew S.; Israelsen, Mads; Krag, Aleksander

2017-01-01

) and abdominal pain (RR 1.54, 95% CI 0.97 to 2.43; 294 participants; low-quality evidence). We identified one ongoing trial on terlipressin versus placebo in participants with cirrhosis, ascites, and hepatorenal syndrome type 1. Three RCTs reported funding from a pharmaceutical company. The remaining trials did...... version of this systematic review found a potential beneficial effect of terlipressin on mortality and renal function in people with cirrhosis and hepatorenal syndrome. Objectives To assess the beneficial and harmful effects of terlipressin versus placebo/no intervention for people with cirrhosis...... until 21 November 2016. Selection criteria Randomised clinical trials (RCTs) involving participantswith cirrhosis and type 1 or type 2 hepatorenal syndrome allocated to terlipressin versus placebo or no intervention. We allowed co-administration with albumin administered to both comparison groups. Data...

Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

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Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

2008-06-01

Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

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Robinson, Michael; Oakes, Tina Myers; Raskin, Joel; Liu, Peng; Shoemaker, Scarlett; Nelson, J Craig

2014-01-01

To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights

The power and value of placebo and nocebo in painful osteoarthritis.

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Dieppe, P; Goldingay, S; Greville-Harris, M

2016-11-01

This paper reviews some recent advances in our understanding of the effects of sham or dummy interventions on pain and other symptoms in osteoarthritis (OA), and outlines two new approaches to the investigation of placebo and nocebo effects. We argue that the placebo effect provides us with a valuable way of investigating the nature of conditions like OA. For example, by examining which symptoms, biochemical markers or imaging features do or do not respond to placebo, we might learn more about the relationships between pathology and symptoms in OA. Placebo and nocebo effects are positive or negative outcomes resulting from the human interactions and contexts in which healthcare consultations take place. Subtle changes in behaviours and the environments in which consultations take place can have major effects on pain and other symptoms being experienced by people with OA. Nocebo effects are particularly powerful, leading to many health-care professionals (HCPs) causing unintended harm to their clients. Based on our own research, we conclude that beneficial outcomes are most likely to occur when both the (HCP) and the client feel safe and relaxed, and when the experiences of the client are validated by the (HCP). These findings have important implications for clinical practice. We believe that research in this field needs to be 'trans-disciplinary', escaping from the constraints of the purely biomedical, deterministic, positivist paradigm of most medical research. We provide the example of our own work which combines performance studies and scholarship, with psychology and medicine. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Disability and pain after cortisone versus placebo injection for trapeziometacarpal arthrosis and de Quervain syndrome

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Makarawung, Dennis J. S.; Becker, Stéphanie J. E.; Bekkers, Stijn; Ring, David

2013-01-01

This study tested the null hypothesis that type of injection (corticosteroid vs. placebo) is not a predictor of arm-specific disability as measured with the Disabilities of Arm, Shoulder and Hand questionnaire 1 to 3 months after injection of dexamethasone or placebo for treatment of

The Effect of Korean Red Ginseng on Sexual Function in Premenopausal Women: Placebo-Controlled, Double-Blind, Crossover Clinical Trial

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Ho Seok Chung

2015-01-01

Full Text Available This study investigated whether Korean red ginseng (KRG extracts could improve sexual function in premenopausal women. Forty-one premenopausal women participated in this placebo-controlled, double-blind, and crossover clinical study with administration of either three ginseng capsules (1 g per capsule or placebo daily. After 8 weeks of medication of KRG or placebo, medication was changed for the subjects to placebo or KRG after 2 weeks of washout period. The efficacy of KRG extracts was measured by using Female Sexual Function Index (FSFI. Results. Twenty-three women completed the study. Total FSFI scores increased after KRG treatment (from 20.13±2.87 to 23.98±4.10, p=0.015 and placebo treatment (from 20.06±2.64 to 23.78±3.28, p=0.003. However, this change was not significantly different between the two groups (p=0.702. KRG treatment significantly improved sexual desire, arousal, orgasm, and satisfaction domains; however, there was no treatment effect compared with placebo. There was a case of gastric discomfort after taking KRG extracts. Oral administration of KRG extracts improved sexual function in premenopausal women; however, there were no statistical significant changes compared to placebo. It implies that KRG extracts have a substantial placebo effect in premenopausal women with sexual dysfunction.

Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial Reatogenicidade de vacinas contra febre amarela em estudo randomizado, controlado com placebo

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Luiz Antonio Bastos Camacho

2005-06-01

Full Text Available OBJECTIVE: To compare the reactogenicity of three yellow fever (YF vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots and placebo. METHODS: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil were administered ("day 0" following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests. RESULTS: Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.OBJETIVO: Comparar a reatogenicidade de três vacinas contra a febre amarela (FA das sub-cepas WHO-17D e 17DD (diferentes lotes-semente, e placebo. MÉTODOS: Foram recrutados 1.087 adultos elegíveis para vacinação contra FA no Rio de Janeiro, RJ, Brasil. Vacinas produzidas por Bio

Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial.

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Boeke, A J; Dekker, J H; van Eijk, J T; Kostense, P J; Bezemer, P D

1993-01-01

OBJECTIVE--To compare the effect of lactic acid locally, metronidazole orally and placebo in women with bacterial vaginosis. DESIGN--Randomised clinical trial. SETTING--30 general practices in the Netherlands. PATIENTS--125 women consulting the general practitioner for symptomatic bacterial vaginosis. MAIN OUTCOME MEASURES--Duration of subjective symptoms, recurrence of symptoms, clinically diagnosed cure, adverse events. RESULTS--Survival analysis showed a significantly faster disappearance of symptoms in the metronidazole category compared with both lactic acid and placebo (p = 0.0005 metronidazole v placebo, p = 0.0002 metronidazole v lactic acid p = 0.6521 lactic acid v placebo [The stratified Mantel Cox test]). The median duration until absence of symptoms was 21 days for metronidazole and 80 days for placebo. Disappearance of symptoms did not occur in 50% of the lactic acid group in 90 days. Recurrence rates of symptoms were similar over the treatment categories (p = 0.13 metronidazole v placebo and p = 0.12 lactic acid v placebo). After 2 weeks cure rates (cure defined as less than three of four clinical criteria present) were 83%, 49% and 47% for metronidazole, lactic acid and placebo category respectively. At that time cure rates (cure defined as none of three clinical criteria present) were 10%, 0% and 3%. After four weeks and three months these figures were: 55%, 20%, 20% and 64%, 28%, 28%. No differences in adverse events were found between the three interventions. CONCLUSIONS--Lactic acid suppositories are ineffective, metronidazole capsules are effective on signs and symptoms in bacterial vaginosis. A considerable proportion of the patients recover without active medication. PMID:8244360

Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers

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E. Tiralongo

2012-01-01

Full Text Available Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P<0.0005. However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P=0.05 during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.

A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state.

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Ashwin Patkar

Full Text Available OBJECTIVE: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD. METHODS: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE, while also meeting 2 or 3 (but not more nor less DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. RESULTS: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038. Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036. Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. CONCLUSIONS: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. TRIAL REGISTRATION: Clinicaltrials.gov NCT00490542.

A systematic review found no consistent difference in effect between more and less intensive placebo interventions

DEFF Research Database (Denmark)

Fässler, Margrit; Meissner, Karin; Kleijnen, Jos

2015-01-01

this hypothesis. STUDY DESIGN AND SETTING: Eligible trials were identified through electronic database searches and citation tracking up to February 2013. Placebo interventions in a trial were categorized into a more intense and a less intense intervention based on complexity, invasiveness, or route...... intense and the less intense placebo intervention, four studies found differences for single outcomes, and one study consistently reported significantly larger effects of the more intense placebo. An explorative meta-analysis yielded a standardized mean difference -0.22 (95% confidence interval: -0.46, 0...

Choto-san in the treatment of vascular dementia: a double-blind, placebo-controlled study.

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Terasawa, K; Shimada, Y; Kita, T; Yamamoto, T; Tosa, H; Tanaka, N; Saito, Y; Kanaki, E; Goto, S; Mizushima, N; Fujioka, M; Takase, S; Seki, H; Kimura, I; Ogawa, T; Nakamura, S; Araki, G; Maruyama, I; Maruyama, Y; Takaori, S

1997-03-01

In an earlier placebo-controlled study, we demonstrated that a kampo (Japanese herbal) medicine called Choto-san (Diao-Teng-San in Chinese) was effective in treating vascular dementia. To evaluate its efficacy using more objective criteria, we carried out a multi-center, double-blind study of Choto-san extract (7.5 g/day) and a placebo, each given three times a day for 12 weeks to patients suffering from this condition. The study enrolled and analyzed 139 patients, 50 males and 89 females, with a mean age of 76.6 years. Choto-san was statistically superior to the placebo in global improvement rating, utility rating, global improvement rating of subjective symptoms, global improvement rating of psychiatric symptoms and global improvement rating of disturbance in daily living activities. Such items as spontaneity of conversation, lack of facial expression, decline in simple mathematical ability, global intellectual ability, nocturnal delirium, sleep disturbance, hallucination or delusion, and putting on and taking off clothes were significantly improved at one or more evaluation points in those taking Choto-san compared to those taking the placebo. Furthermore, the change in revised version of Hasegawa's dementia scale from the beginning point in Choto-san group was tended to be higher than that in placebo group with no statistical significance. These results suggest that Choto-san is effective in the treatment of vascular dementia. Copyright © 1997 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.

Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial

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Andrew Scholey

2017-02-01

Full Text Available Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6, in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171 were randomized (1:1 to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.

Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China.

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He, Zhong; Chen, Rong; Zhou, Yingfang; Geng, Li; Zhang, Zhenyu; Chen, Shuling; Yao, Yanjun; Lu, Junli; Lin, Shouqing

2009-05-20

To investigate the efficacy and safety of VAC BNO 1095 extract in Chinese women suffering from moderate to severe premenstrual syndrome (PMS). Prospective, double-blind, placebo controlled, parallel-group, multi-center clinical trial design was employed. After screening and preparation phase lasting three cycles, Eligible patients were randomly assigned into treatment or placebo groups and had treatment with VAC extract or placebo for up to three cycles. Efficacy was assessed using the Chinese version PMS-diary (PMSD) and PMTS. Two hundred and seventeen women were eligible to enter the treatment phase (TP) and were randomly assigned into the treatment group (108) or the placebo group (109), 208 provided the efficacy data (treatment 104, placebo 104), and 202 completed the treatment phase (treatment 101, placebo 101). The mean total PMSD score decreased from 29.23 at baseline (0 cycle) to 6.41 at the termination (3rd cycle) for the treatment group and from 28.14 at baseline (0 cycle) to 12.64 at the termination (3rd cycle) for the placebo group. The total PMSD score of 3rd cycle was significantly lower than the baseline in both groups (pVitex agnus castus (VAC BNO 1095 corresponding to 40mg herbal drug) is a safe, well tolerated and effective drug of the treatment for Chinese women with the moderate to severe PMS.

Do placebo expectations influence perceived exertion during physical exercise?

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Hendrik Mothes

Full Text Available This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a the effects of exercise and b the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

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Emerson, Nichole M.; Farris, Suzan R.; Ray, Jenna N.; Jung, Youngkyoo; McHaffie, John G.; Coghill, Robert C.

2015-01-01

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p Mindfulness meditation reduced pain intensity (p = 0.032) and pain unpleasantness (p Mindfulness meditation also reduced pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia.

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Zeidan, Fadel; Emerson, Nichole M; Farris, Suzan R; Ray, Jenna N; Jung, Youngkyoo; McHaffie, John G; Coghill, Robert C

2015-11-18

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p pain intensity (p = 0.032) and pain unpleasantness (p pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain modulation. Recent findings have demonstrated that mindfulness meditation

Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.

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Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

2015-08-01

To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. RhEPO 40,000 IU fortnightly did not change the course of ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A double-blind randomized placebo-controlled pilot study of neuropsychiatric adverse events in abstinent smokers treated with varenicline or placebo.

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Garza, Dahlia; Murphy, Michael; Tseng, Li-Jung; Riordan, Henry J; Chatterjee, Anjan

2011-06-01

Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation. There have been spontaneous postmarketing reports of neuropsychiatric adverse events (NPAEs) in smokers without a history of psychiatric illness quitting with varenicline. One hundred ten smokers without history of psychiatric illness (screened by Structured Clinical Interview for DSM-IV) were randomized to 12 weeks of varenicline 1 mg twice daily (n = 55) or placebo. Adverse events were solicited systematically. Depressive symptoms, anxiety, aggression, and irritability were measured at baseline and weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Scale (HAM-A), and the Overt Aggression Scale-Modified (OAS-M). The Profile of Mood States (POMS) was administered daily. Mixed-model analysis of repeated measures was conducted to compare mean changes in scores between groups across study periods. Participants' mean baseline characteristics were 33 years of age, 22 cigarettes/day and Fagerström Test for Nicotine Dependence score > 7. Reported NPAEs were similar between groups. No suicidal events were reported. There were no significant differences between groups for the MADRS (treatment difference vs. placebo = .03, 95% confidence interval [CI] -.68-.73; NS), HAM-A (treatment difference [TD] = .14, 95% CI -.62-.90; NS), OAS-M Aggression subscale (TD = .5, 95% CI -1.18-2.18; NS), OAS-M Irritability subscale (TD = .08, 95% CI -.17-.34; NS), and the POMS total scores (TD = .5, 95% CI -.52-1.53; NS). There were no significant differences between groups on measures of depressive symptoms, anxiety, or aggression/hostility. Systematically solicited NPAEs were similar between the varenicline and placebo groups. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan.

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Asakura, Satoshi; Hayano, Taiji; Hagino, Atsushi; Koyama, Tsukasa

2016-01-01

This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). Patients aged 18-64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. This study has the www.japic.or.jp identifier: JapicCTI-121842. For the primary efficacy endpoint, the difference from placebo in the LSAS-J was -3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of -9.8 (p escitalopram 10 mg) and -10.1 (p escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.

Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study.

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Safarinejad, Mohammad Reza

2005-01-01

To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P Urtica dioica group (from 40.1 cc initially to 36.3 cc; P Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

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Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

The efficacy of agomelatine in elderly patients with recurrent major depressive disorder: a placebo-controlled study.

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Heun, Reinhard; Ahokas, Antti; Boyer, Patrice; Giménez-Montesinos, Natalia; Pontes-Soares, Fernando; Olivier, Valérie

2013-06-01

The present placebo-controlled study evaluated the efficacy, tolerability, and safety of 8-week treatment with agomelatine (25-50 mg/d by mouth) in elderly patients with major depressive disorder (MDD). Elderly outpatients aged ≥ 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD (DSM-IV-TR) were recruited in 27 clinical centers in Argentina, Finland, Mexico, Portugal, and Romania from November 2009 to October 2011. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17) total score. A total of 222 elderly patients entered the study (151 in the agomelatine group, 71 in the placebo group), including 69 patients aged 75 years and older. Agomelatine improved depressive symptoms in the elderly population, as evaluated by the HDRS17 total score, in terms of last postbaseline value (agomelatine-placebo difference: mean estimate [standard error] = 2.67 [1.06] points; P = .013) and response to treatment (agomelatine, 59.5%; placebo, 38.6%; P = .004). The agomelatine-placebo difference according to the Clinical Global Impressions-Severity of Illness scale (CGI-S) score was 0.48 (0.19). The agomelatine-placebo difference (estimate [standard error]) for remission on the HDRS17 was 6.9% (4.7%) and did not achieve statistical significance (P = .179, post hoc analysis). Clinically relevant effects of agomelatine were confirmed on all end points in the subset of severely depressed patients (HDRS17 total score ≥ 25 and CGI-S score ≥ 5 at baseline). Agomelatine was well tolerated by patients, with only minimal distinctions from placebo. The present study provides the first evidence that an 8-week treatment with agomelatine 25-50 mg/d efficiently relieves depressive symptoms and is well tolerated in elderly depressed patients older than 65 years. Controlled-Trials.com identifier: ISRCTN57507360. © Copyright 2011 Physicians Postgraduate Press, Inc.

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

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Shah, Gaurang R; Chaudhari, Manojkumar V; Patankar, Suresh B; Pensalwar, Shrikant V; Sabale, Vilas P; Sonawane, Navneet A

2012-09-15

Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial.

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Morice, Alyn H; McGarvey, Lorcan; Pavord, Ian D; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S

2017-07-01

To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. ClinicalTrials.gov: NCT01656668.

A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

Science.gov (United States)

Henderson, D C; Fan, X; Copeland, P M; Borba, C P; Daley, T B; Nguyen, D D; Zhang, H; Hayden, D; Freudenreich, O; Cather, C; Evins, A E; Goff, D C

2007-02-01

This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

EFFICACY OF CITALOPRAM IN TREATMENT OF PATHOLOGICAL SKIN PICKING, A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

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M Arbabi

2008-11-01

Full Text Available "nVarious studies suggest that selective serotonin reuptake inhibitors (SSRIs may be useful in treating pathological skin picking (PSP. This study sought to assess effectiveness of citalopram in comparison with placebo in treating PSP. Forty five individuals with PSP were recruited in a four-week, randomized clinical trial of citalopram (20 mg/day in comparison with placebo. Study measures assessing skin picking severity, mental health status, obsessive compulsive disorder and quality of life were given at baseline, weeks 2 and 4. PSP severity, general health status, obsession-compulsion severity and quality of life level were similar between two groups at baseline (P > 0.05. Treatment analyses revealed significant improvements in quality of life, general health status and obsession-compulsion severity in citalopram group compared to placebo group (P < 0.05. Mean PSP severity reduction in citalopram group was more than placebo group but this difference was not significant. Citalopram can improve general health status and quality of life in individuals with PSP but its effect on skin picking behavior doesn't differ significantly with placebo. Other trials with longer time are needed to determine the exact efficacy of citalopram on PSP

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

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Bone Kerry M

2009-06-01

Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

Placebo analgesia and reward processing: integrating genetics, personality, and intrinsic brain activity.

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Yu, Rongjun; Gollub, Randy L; Vangel, Mark; Kaptchuk, Ted; Smoller, Jordan W; Kong, Jian

2014-09-01

Our expectations about an event can strongly shape our subjective evaluation and actual experience of events. This ability, applied to the modulation of pain, has the potential to affect therapeutic analgesia substantially and constitutes a foundation for non-pharmacological pain relief. A typical example of such modulation is the placebo effect. Studies indicate that placebo may be regarded as a reward, and brain activity in the reward system is involved in this modulation process. In the present study, we combined resting-state functional magnetic resonance imaging (rs-fMRI) measures, genotype at a functional COMT polymorphism (Val158Met), and personality measures in a model to predict the magnitude of placebo conditioning effect indicated by subjective pain rating reduction to calibrated noxious stimuli. We found that the regional homogeneity (ReHo), an index of local neural coherence, in the ventral striatum, was significantly associated with conditioning effects on pain rating changes. We also found that the number of Met alleles at the COMT polymorphism was linearly correlated to the suppression of pain. In a fitted regression model, we found the ReHo in the ventral striatum, COMT genotype, and Openness scores accounted for 59% of the variance in the change in pain ratings. The model was further tested using a separate data set from the same study. Our findings demonstrate the potential of combining resting-state connectivity, genetic information, and personality to predict placebo effect. Copyright © 2014 Wiley Periodicals, Inc.

Male hormonal contraception: a double-blind, placebo-controlled study.

NARCIS (Netherlands)

Mommers, E.; Kersemaekers, W.M.; Elliesen, J.; Kepers, M.; Apter, D.; Behre, H.M.; Beynon, J.; Bouloux, P.M.; Costantino, A.; Gerbershagen, H.P.; Gronlund, L.; Heger-Mahn, D.; Huhtaniemi, I.; Koldewijn, E.L.; Lange, C.; Lindenberg, S.; Meriggiola, M.C.; Meuleman, E.J.H.; Mulders, P.F.A.; Nieschlag, E.; Perheentupa, A.; Solomon, A.; Vaisala, L.; Wu, F.C.; Zitzmann, M.

2008-01-01

BACKGROUND: This study was performed to assess spermatogenesis suppression and safety of a new combination of an etonogestrel (ENG) implant combined with testosterone undecanoate (TU) injections for male contraception. This is the first large placebo-controlled study for male hormonal contraception.

Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study

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Gunzler, Steven A.; Koudelka, Caroline; Carlson, Nichole E.; Pavel, Misha; Nutt, John G.

2011-01-01

Objective To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state. Design Randomized, double-blind, placebo-controlled, crossover clinical trial. Setting Academic movement disorders center. Patients Patients with Parkinson disease and motor fluctuations. Intervention Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (sub-threshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 μg/kg/h every 2 hours and 25 μg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 μg/kg/h every 2 hours and 100 μg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days. Main Outcome Measures Finger and foot tapping rates. Results There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P<.001) and trended toward increasing finger tapping compared with placebo infusions. Conclusions Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that pre-synaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease. PMID:18268187

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

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Jenkins TM

2012-07-01

Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

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McGraw T

2016-07-01

Full Text Available Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC of polyethylene glycol (PEG 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g ASC or placebo solution for 14 days. The study comprised a screening period (visit 1, endoscopy procedure (visits 2 and 3, and follow-up telephone calls 30 days post-treatment. Safety end points included adverse events (AEs, clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions.Results: A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment or visit 3 (after treatment. Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo – nonsignificant difference of -7.5% (95% CI: -21.3, 6.3 between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

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Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

2015-02-01

Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in

Los efectos placebo de la relación médico-paciente The placebo effects of the physician-patient relationship

Directory of Open Access Journals (Sweden)

Ricardo González Menéndez

2004-12-01

Full Text Available Luego de breves comentarios históricos que abordan la influencia del primer modelo psicoterapéutico en la ya superada tendencia a considerar la psicoterapia como fuera del alcance del médico generalista, se comentan los aportes de Carl Rogers al enfatizar la trascendencia de las actitudes del facultativo en la relación interpersonal y su mayor trascendencia sobre los métodos y recursos psicoterapéuticos elegidos. Se destaca igualmente los resultados similares obtenidos en estudios orientados a comparar diferentes modalidades psicoterapéuticas, hallazgos que ratifican la importancia de los vínculos afectivos establecidos entre el profesional de la salud y sus pacientes cuando la relación médico-paciente es exitosa. Se describen los 6 efectos placebo de esta relación descritos por Shapiro y Frank desde 1971 y se agregan otros 4 surgidos de las reflexiones del equipo de trabajo del autor. Se insiste en que las limitaciones iniciales establecidas al médico generalista sobre sus responsabilidades psicoterapéuticas, resultan actualmente insostenibles para los facultativos capaces de sensibilizarse ante el drama humano de un paciente. Se concluye que las pontecialidades terapéuticas implícitas en los efectos placebos descritos justifican cada vez más la incursión del médico generalista en la relación de ayuda psicológica.After some brief historical comments dealing with the influence of the first psychotherapeutic model on the already overcome trend to consider psychotherapy as out of the reach of the general physcian, the contributions of Carl Rogers are exposed on emphasizing the transcendency of the physcian's attitudes in the interpersonal relation and its greater transcendence in relation to the selected psychotherapeutic methods and resources. The similar results attained in the studies oriented to compare different psychotherapeutic modalities are also stressed. These findings ratify the importance of the affective links

A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision

DEFF Research Database (Denmark)

Ågren, Magnus S.; Ostenfeld, Ulla; Kallehave, Finn Lasse

2006-01-01

The purpose of this randomized, double-blind, placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years, were centrally randomized to either treatment with 3% zinc oxide...... (n = 33) or placebo (n = 31) by concealed allocation. Patients were followed with strict recording of beneficial and harmful effects including masked assessment of time to complete wound closure. Analysis was carried out on an intention-to-treat basis. Median healing times were 54 days (interquartile...... range 42-71 days) for the zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc oxide increased (p placebo...

Minoxidil 2% lotion for eyebrow enhancement: a randomized, double-blind, placebo-controlled, spilt-face comparative study.

Science.gov (United States)

Lee, Saridpong; Tanglertsampan, Chuchai; Tanchotikul, Mingkwan; Worapunpong, Nigun

2014-02-01

Topical minoxidil has been successfully used to treat androgenetic alopecia. It can also be applied to enhance eyebrows. However, there is no study comparing minoxidil lotion with placebo for eyebrow enhancement. In this trial, we determined the efficacy and safety of minoxidil 2% lotion for eyebrow enhancement compared with placebo. Forty patients were randomized for minoxidil on the eyebrow on one side of the face and placebo on the other. Efficacy was evaluated by global photographic assessment, eyebrow diameter, eyebrow count and subject's satisfaction. Side-effects were also evaluated. Thirty-nine patients (97.5%) completed the study. After 16 weeks, the minoxidil group achieved significantly better results in all measured outcomes compared to the placebo group. Side-effects were minor and did not preclude patients from continuing the study. Our study suggests that minoxidil 2% lotion is a safe and effective treatment for eyebrow hypotrichosis. © 2014 Japanese Dermatological Association.

A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.

Science.gov (United States)

Victor, Ronald G; Sweeney, H Lee; Finkel, Richard; McDonald, Craig M; Byrne, Barry; Eagle, Michelle; Goemans, Nathalie; Vandenborne, Krista; Dubrovsky, Alberto L; Topaloglu, Haluk; Miceli, M Carrie; Furlong, Pat; Landry, John; Elashoff, Robert; Cox, David

2017-10-24

To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD). Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg -1 ·d -1 , tadalafil 0.6 mg·kg -1 ·d -1 , or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome. Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil ( p = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil ( p = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state. Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age. NCT01865084. This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study123

Science.gov (United States)

Velmurugan, Shanti; Gan, Jasmine Ming; Rathod, Krishnaraj S; Khambata, Rayomand S; Ghosh, Suborno M; Hartley, Amy; Van Eijl, Sven; Sagi-Kiss, Virag; Chowdhury, Tahseen A; Curtis, Mike; Kuhnle, Gunter GC; Wade, William G; Ahluwalia, Amrita

2016-01-01

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a

Dopaminergic tone does not influence pain levels during placebo interventions in patients with chronic neuropathic pain.

Science.gov (United States)

Skyt, Ina; Moslemi, Kurosh; Baastrup, Cathrine; Grosen, Kasper; Benedetti, Fabrizio; Petersen, Gitte L; Price, Donald D; Hall, Kathryn T; Kaptchuk, Ted J; Svensson, Peter; Jensen, Troels S; Vase, Lene

2017-10-23

Placebo effects have been reported in patients with chronic neuropathic pain. Expected pain levels and positive emotions are involved in the observed pain relief, but the underlying neurobiology is largely unknown. Patients with neuropathic pain are highly motivated for pain relief, and as motivational factors such as expectations of reward, as well as pain processing in itself, are related to the dopaminergic system, it can be speculated that dopamine release contributes to placebo effects in neuropathic pain. Nineteen patients with neuropathic pain after thoracic surgery were tested during a placebo intervention consisting of open and hidden applications of the pain-relieving agent lidocaine (2 mL) and no treatment. The dopamine antagonist haloperidol (2 mg) and the agonist levodopa/carbidopa (100/25 mg) were administered to test the involvement of dopamine. Expected pain levels, desire for pain relief, and ongoing and evoked pain were assessed on mechanical visual analog scales (0-10). Significant placebo effects on ongoing (P ≤ 0.003) and evoked (P ≤ 0.002) pain were observed. Expectancy and desire accounted for up to 41.2% and 71.5% of the variance in ongoing and evoked pain, respectively, after the open application of lidocaine. We found no evidence for an effect of haloperidol and levodopa/carbidopa on neuropathic pain levels (P = 0.071-0.963). Dopamine seemed to influence the levels of expectancy and desire, yet there was no evidence for indirect or interaction effects on the placebo effect. This is the first study to suggest that dopamine does not contribute to placebo effects in chronic neuropathic pain.

A placebo-controlled investigation of synaesthesia-like experiences under LSD.

Science.gov (United States)

Terhune, Devin B; Luke, David P; Kaelen, Mendel; Bolstridge, Mark; Feilding, Amanda; Nutt, David; Carhart-Harris, Robin; Ward, Jamie

2016-07-29

The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.

Science.gov (United States)

Panés, Julian; Sandborn, William J; Schreiber, Stefan; Sands, Bruce E; Vermeire, Séverine; D'Haens, Geert; Panaccione, Remo; Higgins, Peter D R; Colombel, Jean-Frederic; Feagan, Brian G; Chan, Gary; Moscariello, Michele; Wang, Wenjin; Niezychowski, Wojciech; Marren, Amy; Healey, Paul; Maller, Eric

2017-06-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (ptofacitinib. NCT01393626 and NCT01393899. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence.

Science.gov (United States)

Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2017-08-01

Because electronic cigarettes (e-cigs) containing nicotine may relieve smoking abstinence symptoms similar to nicotine replacement therapy medication, we used within-subjects designs to test these effects with a first-generation e-cig in nonquitting and quitting smokers. In Study 1, 28 nontreatment-seeking smokers abstained overnight prior to each of 3 sessions. Minnesota Nicotine Withdrawal Scale (MNWS) withdrawal (and craving item) relief was assessed following 4 exposures (each 10 puffs) over 2 hr to e-cigs that either did (36 mg/ml) or did not (i.e., placebo, 0 mg/ml) contain nicotine or after no e-cig. Relief was greater after nicotine versus placebo e-cig (p < .05) but not after placebo versus no e-cig, showing relief was due to nicotine per se and not simple e-cig use behavior. Using a crossover design in Study 2, smokers preparing to quit soon engaged in 2 experimental 4-day quit periods on separate weeks. In weeks 1 and 3, all received a nicotine or placebo e-cig on Monday to use ad libitum while trying to abstain from smoking on Tuesday through Friday. (Week 2 involved resumption of ad libitum smoking.) MNWS and Questionnaire of Smoking Urges (QSU) craving were assessed at daily visits following 24-hr abstinence. Of 17 enrolled, 12 quit for ≥24 hr at least once, allowing test of relief because of e-cig use on quit days. Withdrawal and craving were reduced because of nicotine versus placebo e-cig use (both p < .05). In sum, compared with placebo e-cigs, nicotine e-cigs can relieve smoking abstinence symptoms, perhaps in a manner similar to Food and Drug Administration-approved nicotine replacement therapy products, although much more research with larger samples is needed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Ozenoxacin 1% cream in the treatment of impetigo: a multicenter, randomized, placebo- and retapamulin-controlled clinical trial.

Science.gov (United States)

Gropper, Savion; Albareda, Nuria; Chelius, Klaus; Kruger, Dawie; Mitha, Ismail; Vahed, Yacoob; Gani, Mashra; García-Alonso, Fernando

2014-01-01

We compared the efficacy and safety of ozenoxacin (a new nonfluorinated quinolone) 1% cream with placebo in the treatment of impetigo. In a randomized, double-blind, multicenter study, patients received ozenoxacin cream or placebo cream twice daily for 5 days (a third group received retapamulin 1% ointment as a control). Clinical, microbiological and laboratory evaluations were performed during follow-up (over 2 weeks). Ozenoxacin was superior to placebo (success rate 34.8 vs 19.2%; p = 0.003). Microbiological success was 70.8% for ozenoxacin and 38.2% for placebo after 3-4 days and 79.2% versus 56.6% after 6-7 days. Ozenoxacin produced more rapid microbiological clearance than retapamulin. All treatments were well tolerated. Ozenoxacin 1% cream was effective and safe in the treatment of impetigo.

A placebo-controlled comparison of ketamine with pethidine for the ...

African Journals Online (AJOL)

Southern African Journal of Anaesthesia and Analgesia ... of ketamine when compared with pethidine and placebo for the prevention of postanaesthetic shivering. ... Pain was assessed and recorded by means of a visual analogue scale.

A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa

DEFF Research Database (Denmark)

Miller, I; Lynggaard, C D; Lophaven, S

2011-01-01

BACKGROUND: Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. OBJECTIVES: To test the efficacy of adalimumab in HS. METHODS: This was a prospective, randomized, double-blinded, placebo-controlled,......BACKGROUND: Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. OBJECTIVES: To test the efficacy of adalimumab in HS. METHODS: This was a prospective, randomized, double-blinded, placebo......-controlled, two-centre clinical trial conducted in Denmark. Inclusion criteria were age above 18 years and a clinical diagnosis of moderate to severe HS defined as Hurley stage II or III for at least 6 months. The patients were randomized 1:2 (placebo/active). Actively treated patients received adalimumab 80 mg...... subcutaneously (s.c.) at baseline followed by 40 mg s.c. every other week for 12 weeks. Placebo-treated patients received identical-looking injections with no active ingredient. The medicine was dispensed in sequentially numbered computer-randomized containers. Participants, care givers and those assessing...

Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial.

Science.gov (United States)

Guerdjikova, Anna I; McElroy, Susan L; Winstanley, Erin L; Nelson, Eric B; Mori, Nicole; McCoy, Jessica; Keck, Paul E; Hudson, James I

2012-03-01

This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary outcome measure was weekly binge eating day frequency. In the primary analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02), weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass index and measures of eating pathology, depression, and anxiety did not differ between the two groups. Duloxetine may be effective for reducing binge eating, weight, and global severity of illness in BED with a comorbid current depressive disorder, but this finding needs confirmation in larger, placebo-controlled trials. Copyright © 2011 Wiley Periodicals, Inc.

Prophylaxis of irradiation-induced Diarrhea with smectite. Results of a placebo-controlled investigation

International Nuclear Information System (INIS)

Hombrink, J.; Froehlich, D.; Glatzel, M.; Krauss, A.; Thiel, H.J.; Meier, J.; Hamann, D.; Muecke, R.; Glaser, F.H.; Koest, S.

2000-01-01

Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (=Colina trademark ) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2x6 g smectite daily and 91 patients received 2x6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (≥3 pappy stools). Results: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume ≤837.5 ml, the other with a small bowel volume >837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. Conclusion: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis. (orig.) [de

The psychological behaviorism theory of pain and the placebo: its principles and results of research application.

Science.gov (United States)

Staats, Peter S; Hekmat, Hamid; Staats, Arthur W

2004-01-01

The psychological behaviorism theory of pain unifies biological, behavioral, and cognitive-behavioral theories of pain and facilitates development of a common vocabulary for pain research across disciplines. Pain investigation proceeds in seven interacting realms: basic biology, conditioned learning, language cognition, personality differences, pain behavior, the social environment, and emotions. Because pain is an emotional response, examining the bidirectional impact of emotion is pivotal to understanding pain. Emotion influences each of the other areas of interest and causes the impact of each factor to amplify or diminish in an additive fashion. Research based on this theory of pain has revealed the ameliorating impact on pain of (1) improving mood by engaging in pleasant sexual fantasies, (2) reducing anxiety, and (3) reducing anger through various techniques. Application of the theory to therapy improved the results of treatment of osteoarthritic pain. The psychological behaviorism theory of the placebo considers the placebo a stimulus conditioned to elicit a positive emotional response. This response is most powerful if it is elicited by conditioned language. Research based on this theory of the placebo that pain is ameliorated by a placebo suggestion and augmented by a nocebo suggestion and that pain sensitivity and pain anxiety increase susceptibility to a placebo.

Antioxidative Activity of Onion Peel Extract in Obese Women: A Randomized, Double-blind, Placebo Controlled Study.

Science.gov (United States)

Kim, Kyung-Ah; Yim, Jung-Eun

2015-09-01

Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman. This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively. Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption. These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women.

Placebo substitution for tnethyldopa in geriatric hypertensive patients

African Journals Online (AJOL)

and the benefit of treatment is still disputed.6 The aim of this study was to substitute a matching placebo for methyldopa in order to evaluate the effect of removal of a drug from the antihypertensive regimen of elderly patients without concomitantly inducing a sense of in- security. Sex (female/male) 16/2. Mean age (yrs). 75,7.

A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

OpenAIRE

Little, A; Levy, R; Chuaqui-Kidd, P; Hand, D

1985-01-01

The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improve...

A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder.

Science.gov (United States)

Westenberg, Herman G M; Stein, Dan J; Yang, Haichen; Li, David; Barbato, Luigi M

2004-02-01

This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

Science.gov (United States)

Devanand, D P; Nobler, Mitchell S; Cheng, Jocelyn; Turret, Nancy; Pelton, Gregory H; Roose, Steven P; Sackeim, Harold A

2005-01-01

The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

A Randomized Double-blind Placebo-controlled Trial to Assess the Effect of Tamarind seed in Premature Ejaculation

Directory of Open Access Journals (Sweden)

Abdulla Homayuonfar

2018-01-01

Full Text Available Background: This randomized clinical trial was aimed to evaluate the effect of oral use of tamarind seed powder as an herbal product in patients affected by premature ejaculation (PE. Materials and Methods: In this study, 75 patients randomized in tamarind group (25 patients received daily 130 mg tamarind seed powder, paroxetine group (25 patients received daily 20 mg paroxetine, and placebo group (25 patients. Patients received the treatment regimen for 4 weeks. The primary outcome was intravaginal ejaculatory latency time (IELT. The secondary outcomes were PE diagnostic tool score, sexual function using International Index of Erectile Function (IIEF, and complications. Studied sexual functions include erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. Results: The mean of IELT in tamarind, paroxetine, and placebo groups at baseline was 35.2 ± 26.5, 38 ± 27.6, and 44 ± 34.9 s and at the end of study was 49.5 ± 48.2, 147.4 ± 209.6, and 46.9 ± 37.6 s, respectively, which in paroxetine group significantly increased compared to other groups. IIEF scores for orgasmic function and intercourse satisfaction for paroxetine after treatment significantly increased than that of other groups. The differences between tamarind and placebo groups for studied variables were not statistically significant. The mean of increases in IELT for tamarind, paroxetine, and placebo groups was 14.35 ± 34.3, 109.4 ± 213.4, and 2.9 ± 9.3 s, respectively, which in paroxetine group was significantly higher than other groups and in tamarind group was significantly higher than placebo. Conclusions: Paroxetine was significantly better than tamarind seed powder and placebo although side effect in paroxetine was more frequent. IELT significantly more increased in tamarind group compared to placebo.

Effect of Zingiber officinale R. rhizomes (ginger on pain relief in primary dysmenorrhea: a placebo randomized trial

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Rahnama Parvin

2012-07-01

Full Text Available Abstract Background Zingiber officinale R. rhizome (ginger is a popular spice that has traditionally been used to combat the effects of various inflammatory diseases. The aim of this study was to evaluate the effects of ginger on pain relief in primary dysmenorrhea. Method This was a randomized, controlled trial. The study was based on a sample of one hundred and twenty students with moderate or severe primary dysmenorrhea. The students were all residents of the dormitories of Shahed University. They were randomly assigned into two equal groups, one for ginger and the other for placebo in two different treatment protocols with monthly intervals. The ginger and placebo groups in both protocols received 500 mg capsules of ginger root powder or placebo three times a day. In the first protocol ginger and placebo were given two days before the onset of the menstrual period and continued through the first three days of the menstrual period. In the second protocol ginger and placebo were given only for the first three days of the menstrual period. Severity of pain was determined by a verbal multidimensional scoring system and a visual analogue scale. Results There was no difference in the baseline characteristics of the two groups (placebo n = 46, ginger n = 56. The results of this study showed that there were significant differences in the severity of pain between ginger and placebo groups for protocol one (P = 0.015 and protocol two (P = 0.029. There was also significant difference in duration of pain between the two groups for protocol one (P = 0.017 but not for protocol two (P = 0.210. Conclusion Treatment of primary dysmenorrhea in students with ginger for 5 days had a statistically significant effect on relieving intensity and duration of pain. Trial registration IRCT201105266206N3

A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis.

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Abzug, Mark J; Michaels, Marian G; Wald, Ellen; Jacobs, Richard F; Romero, José R; Sánchez, Pablo J; Wilson, Gregory; Krogstad, Paul; Storch, Gregory A; Lawrence, Robert; Shelton, Mark; Palmer, April; Robinson, Joan; Dennehy, Penelope; Sood, Sunil K; Cloud, Gretchen; Jester, Penelope; Acosta, Edward P; Whitley, Richard; Kimberlin, David

2016-03-01

Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

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van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; ptofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Efficacy and Safety of Drotaverine Hydrochloride in Children with Recurrent Abdominal Pain: A Randomized Placebo Controlled Trial.

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Narang, Manish; Shah, Dheeraj; Akhtar, Hina

2015-10-01

To evaluate the efficacy and safety of Drotaverine hydrochroride in children with recurrent abdominal pain. Double blind, randomized placebo-controlled trial. Pediatric Gastroenterology clinic of a teaching hospital. 132 children (age 4-12 y) with recurrent abdominal pain (Apley Criteria) randomized to receivedrotaverine (n=66) or placebo (n=66) orally. Children between 4-6 years of age received 10 mL syrup orally (20 mg drotaverine hydrochloride or placebo) thrice daily for 4 weeks while children >6 years of age received one tablet orally (40 mg drotaverine hydrochloride or placebo) thrice daily for 4 weeks. Primary: Number of episodes of pain during 4 weeks of use of drug/placebo and number of pain-free days. Secondary: Number of school days missed during the study period, parental satisfaction (on a Likert scale), and occurrence of solicited adverse effects. Reduction in number of episodes of abdominal pain [mean (SD) number of episodes 10.3 (14) vs 21.6 (32.4); P=0.01] and lesser school absence [mean (SD) number of school days missed 0.25 (0.85) vs 0.71 (1.59); P=0.05] was noticed in children receiving drotaverine in comparison to those who received placebo. The number of pain-free days, were comparable in two groups [17.4 (8.2) vs 15.6 (8.7); P=0.23]. Significant improvement in parental satisfaction score was noticed on Likert scale by estimation of mood, activity, alertness, comfort and fluid intake. Frequency of adverse events during follow-up period was comparable between children receiving drotaverine or placebo (46.9% vs 46.7%; P=0.98). Drotaverine hydrochloride is an effective and safe pharmaceutical agent in the management of recurrent abdominal pain in children.

The Placebo Response in Pediatric Abdominal Pain-Related Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis.

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Hoekman, Daniël R; Zeevenhooven, Judith; van Etten-Jamaludin, Faridi S; Douwes Dekker, Iuke; Benninga, Marc A; Tabbers, Merit M; Vlieger, Arine M

2017-03-01

To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL were searched for systematic reviews and randomized placebo-controlled trials concerning children 4-18 years of age with an abdominal pain-related functional gastrointestinal disorder. The primary outcome was the pooled proportion of subjects assigned to placebo with improvement as defined by the authors. The effect of trial characteristics on the magnitude of the placebo response was investigated using univariate meta-regression analysis. Twenty-one trials were identified. The pooled proportion of subjects with improvement was 41% (95% CI, 34%-49%; 17 studies) and with no pain was 17% (95% CI, 8%-32%; 7 studies). The pooled standardized mean difference on the Faces Pain Scales compared with baseline was -0.73 (95% CI, -1.04 to -0.42; 8 studies). There was significant heterogeneity across studies with respect to both outcomes. Lower dosing frequency (P = .04), positive study (P = .03), longer duration of treatment (P pain. Response on Faces Pain Scales was greater in studies conducted in the Middle East (P = .002), in studies that did not report the randomization schedule (P = .02), and in studies with a higher percentage of females (P = .04). Approximately 41% of children with abdominal pain-related functional gastrointestinal disorders improve on placebo. Several trial characteristics are correlated significantly with the proportion of patients with no pain on placebo and with the magnitude of the placebo response on Faces Pain Scales. These data could be valuable for the design of future studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Moderation of Nicotine Effects on Covert Orienting of Attention Tasks by Poor Placebo Performance and Cue Validity

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Gilbert, David G.; Rzetelny, Adam; Rabinovich, Norka E.

2016-01-01

Introduction and Rationale Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. Method The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. Results Compared to a placebo patch, a 14 mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. Conclusions These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine’s effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement. PMID:27461547

Exposure–response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development

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Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

2015-01-01

No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs. PMID:26392753

Exposure-response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development.

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Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

2015-01-01

No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure-response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure-response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects' sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure-response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs.

Effectiveness of tamsulosin in prevention of post-operative urinary retention: a randomized double-blind placebo-controlled study.

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Madani, Ali Hamidi; Aval, Hamidreza Baghani; Mokhtari, Gholamreza; Nasseh, Hamidreza; Esmaeili, Samaneh; Shakiba, Maryam; Shakiba, Reza Shahrokhi; Seyed Damavand, Seyed Mohamad

2014-01-01

Urinary retention is one of the most common complications contributing to surgical procedures. Recent studies have shown the benefits of alpha-adrenergic blockers in preventing post-operative urinary retention (POUR). The aim of this prospective study was to compare the prophylactic effect of tamsulosin with placebo on postoperative urinary retention. In this randomized placebo controlled, clinical trial, 232 male patients aged 18 to 50 years old admitted to Razi University Hospital for varicocelectomy, inguinal herniorrhaphy, and scrotal surgery were randomly assigned to receive either three doses of 0.4mg tamsulosin (n = 118) or placebo (n = 114), 14 and 2 hours before, and 10 hours after surgery. Patients were closely monitored for the development of urinary retention 24 hours after surgical intervention. The primary endpoint was to investigate the effect of tamsulosin in prevention of post-operative urinary retention during the first 24 hours after surgical intervention. Collected data were analyzed using SPSS software version 18 and the P tamsulosin arm and 114 in placebo arm. POUR in patients who received tamsulosin was significantly lower than placebo, as 5.9% of the patients treated with tamsulosin and 21.1% placebo group, reported urinary retention following surgery (P = 0.001). No serious adverse effects were seen in both groups. This study suggests that short perioperative treatment with tamsulosin can reduce the incidence of urinary retention and the need for catheterization after varicocelectomy, inguinal herniorrhaphy, and scrotal surgery.

Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram.

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Lavretsky, Helen; Siddarth, Prabha; Irwin, Michael R

2010-02-01

This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blinded trial. Forty family caregivers (43-91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient's cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28. The groups were stratified by the diagnosis of major and minor depression. Most outcomes favored escitalopram over placebo. The severity of depression improved, and the remission rate was greater with the drug compared with placebo. Measures of anxiety, resilience, burden, and distress improved on escitalopram compared with placebo. Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample.

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

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Gao, Jian-Wei; Gao, Xue-Min; Zou, Ting; Zhao, Tian-Meng; Wang, Dong-Hua; Wu, Zong-Gui; Ren, Chang-Jie; Wang, Xing; Geng, Nai-Zhi; Zhao, Ming-Jun; Liang, Qiu-Ming; Feng, Xing; Yang, Bai-Song; Shi, Jun-Ling; Hua, Qi

2018-03-01

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group. Copyright© by the Chinese Pharmaceutical Association.

Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial.

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McDonald, Brenna C; Flashman, Laura A; Arciniegas, David B; Ferguson, Robert J; Xing, Li; Harezlak, Jaroslaw; Sprehn, Gwen C; Hammond, Flora M; Maerlender, Arthur C; Kruck, Carrie L; Gillock, Karen L; Frey, Kim; Wall, Rachel N; Saykin, Andrew J; McAllister, Thomas W

2017-08-01

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (PABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.

Response Expectancy and the Placebo Effect.

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Kirsch, Irving

2018-01-01

In this chapter, I review basic tenets of response expectancy theory (Kirsch, 1985), beginning with the important distinction between response expectancies and stimulus expectancies. Although both can affect experience, the effects of response expectancies are stronger and more resistant to extinction than those of stimulus expectancies. Further, response expectancies are especially important to understanding placebo effects. The response expectancy framework is consistent with and has been amplified by the Bayesian model of predictive coding. Clinical implications of these phenomena are exemplified. © 2018 Elsevier Inc. All rights reserved.

Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model.

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Puviani, Luca; Rama, Sidita

2016-07-20

Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of the response to substance intake. It is shown that placebo response can be conceptualized as a reaction of a distributed neural system within the central nervous system. Such a reaction represents an integrated component of the response to open substance administration (or to substance intake) and is updated through "unconditioned stimulus (UCS) revaluation learning". The analysis leads to a theorem, which proves the existence of two distinct quantities coded within the brain, these are the expected or prediction outcome and the reactive response. We show that the reactive response is updated automatically by implicit revaluation learning, while the expected outcome can also be modulated through conscious information processing. Conceptualizing the response to substance intake in terms of UCS revaluation learning leads to the theoretical formulation of a potential neuropharmacological treatment for increasing unlimitedly the effectiveness of a given drug.

The subtle central effect of nutraceuticals: Is it placebo or nocebo?

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Ali I. Al-Gareeb

2015-09-01

Subjects and methods: This is a randomized, double-blind, controlled, and prospective study conducted in the Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq during February 2013. One hundred sixty medical students participated in the study were randomly assigned equally to one of the following groups: Group A: received single dose of nigella sativa oil (500 ml capsule;Group B: received single dose of garlic (500 mg capsule; Group C: received single dose of Coq10 (120 mg capsule and; Group D: received single dose of matching oral placebo (300mg starchc capsule. For all participants, reaction time and flicker fusion threshold were measured by the Leeds psychomotor performance test battery before and after 3 hours of taking the drugs Results: Neither placebo nor nutraceuticals exerted significant effect on total reaction time. Although the recognition reaction time is insignificantly reduced by 2.77% (placebo, 5.83% (Nigella savita, 7.21% (Garlic and 12.64% (CoQ10 from the pretreatment values, they are adversely affect the motor reaction time to reach the significant level in subjects pretreated with Garlic (p=0.02. Conclusion: Nutraceuticals are not free from nocebo effect on psychomotor performance. [J Intercult Ethnopharmacol 2015; 4(3.000: 221-223

A Bayesian perspective on sensory and cognitive integration in pain perception and placebo analgesia.

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Davide Anchisi

Full Text Available The placebo effect is a component of any response to a treatment (effective or inert, but we still ignore why it exists. We propose that placebo analgesia is a facet of pain perception, others being the modulating effects of emotions, cognition and past experience, and we suggest that a computational understanding of pain may provide a unifying explanation of these phenomena. Here we show how Bayesian decision theory can account for such features and we describe a model of pain that we tested against experimental data. Our model not only agrees with placebo analgesia, but also predicts that learning can affect pain perception in other unexpected ways, which experimental evidence supports. Finally, the model can also reflect the strategies used by pain perception, showing that modulation by disparate factors is intrinsic to the pain process.

Umeclidinium bromide versus placebo for people with chronic obstructive pulmonary disease (COPD).

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Ni, Han; Htet, Aung; Moe, Soe

2017-06-20

People with chronic obstructive pulmonary disease (COPD) have poor quality of life, reduced survival, and accelerated decline in lung function, especially associated with acute exacerbations, leading to high healthcare costs. Long-acting bronchodilators are the mainstay of treatment for symptomatic improvement, and umeclidinium is one of the new long-acting muscarinic antagonists approved for treatment of patients with stable COPD. To assess the efficacy and safety of umeclidinium bromide versus placebo for people with stable COPD. We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, the World Health Organization (WHO) trials portal, and the GlaxoSmithKline (GSK) Clinical Study Register, using prespecified terms, as well as the reference lists of all identified studies. Searches are current to April 2017. We included randomised controlled trials (RCTs) of parallel design comparing umeclidinium bromide versus placebo in people with COPD, for at least 12 weeks. We used standard Cochrane methodological procedures. If we noted significant heterogeneity in the meta-analyses, we subgrouped studies by umeclidinium dose. We included four studies of 12 to 52 weeks' duration, involving 3798 participants with COPD. Mean age of participants ranged from 60.1 to 64.6 years; most were males with baseline mean smoking pack-years of 39.2 to 52.3. They had moderate to severe COPD and baseline mean post-bronchodilator forced expiratory volume in one second (FEV 1 ) ranging from 44.5% to 55.1% of predicted normal. As all studies were systematically conducted according to prespecified protocols, we assessed risk of selection, performance, detection, attrition, and reporting biases as low.Compared with those given placebo, participants in the umeclidinium group had a lesser likelihood of developing moderate exacerbations requiring a short course of steroids, antibiotics, or both (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.46 to 0.80; four

A double-blind placebo-controlled trial of maca root as treatment for antidepressant-induced sexual dysfunction in women.

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Dording, Christina M; Schettler, Pamela J; Dalton, Elizabeth D; Parkin, Susannah R; Walker, Rosemary S W; Fehling, Kara B; Fava, Maurizio; Mischoulon, David

2015-01-01

Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126.

A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women

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Christina M. Dording

2015-01-01

Full Text Available Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day in 45 female outpatients (mean age of 41.5 ± 12.5 years with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ. Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo, attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo. Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126.

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study

Directory of Open Access Journals (Sweden)

Shah Gaurang R

2012-09-01

Full Text Available Abstract Background Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP – a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. Methods 78 men aged 25–50 years of age; suffering from mild to moderate erectile dysfunction (ED, participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS, Serum testosterone, Semen analysis, Investigator’s Global assessment and Subjects’ opinion. Results In subjects receiving VXP, the IIEF-Erectile Function (EF scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd IIEF-EF score at baseline increased from 16.08 (2.87 to 25.08 (4.56 in the VXP group versus 15.86 (3.24 to 16.47 (4.25 in the placebo group (P P  Conclusions VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Trial Registration Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009

Ketoprofen gel improves low back pain in addition to IV dexketoprofen: a randomized placebo-controlled trial.

Science.gov (United States)

Serinken, Mustafa; Eken, Cenker; Tunay, Kamil; Golcuk, Yalcin

2016-08-01

Oligoanalgesia is common in emergency departments (EDs), and pain management is of concern for ED physicians. The aim of this study was to reveal the effect of ketoprofen gel in patients presenting with mechanical low back pain to the ED. All the study patients received intravenous dexketoprofen additional to study drugs. After dexketoprofen, 2 g of 2.5% ketoprofen gel or placebo was administered to the site with pain and tenderness. Pain relief at 15 and 30 minutes was measured by visual analog scale scores. Rescue drug need and adverse effects were also recorded. A total of 140 patients were enrolled into the study. The mean age of the study patients was 35±12, and 56% (n=79) of them were male. The mean pain reduction at 30 minutes was 52±18 for ketoprofen gel and 37±17 for placebo, and ketoprofen gel was better than placebo at 30 minutes (mean difference, 16 mm; 95% confidence interval, 10-21). Ten patients (14%) in the placebo group and 2 patients (3%) in the ketoprofen gel group needed rescue drug (P=.35). Ketoprofen gel improves pain in patients presenting with mechanical low back pain to ED at 30 minutes in addition to intravenous dexketoprofen when compared to placebo. Copyright © 2016 Elsevier Inc. All rights reserved.

Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram.

Science.gov (United States)

Bachman, E A; Senapati, S; Sammel, M D; Kalra, S K

2014-06-01

Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group

Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS

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Dorte Glintborg

2018-03-01

Full Text Available Background/aims: Polycystic ovary syndrome (PCOS is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Methods: Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21 or placebo (n = 21. Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH test, 3-h oral glucose tolerance test (OGTT and filled in questionnaires regarding mental health and health-related quality of life (HRQoL: WHO Well-Being Index (WHO-5, Major Depression Inventory (MDI, Short Form 36 (SF-36 and PCOS questionnaire. Results: Included women were aged 31 (6 years (mean (s.d. and had body mass index (BMI 35.8 (6.5 kg/m2 and waist 102 (12 cm. Escitalopram was associated with increased waist (median (quartiles change 1 (0; 3 cm, P = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test, all P < 0.05 vs changes during placebo. Escitalopram had no significant effect on measures of insulin sensitivity, insulin secretion, fasting lipids, mental health or HRQoL. Conclusion: Waist circumference and cortisol levels increased during treatment with escitalopram in women with PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged.

Open-label placebo treatment in chronic low back pain: a randomized controlled trial.

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Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J; Kirsch, Irving

2016-12-01

This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

Science.gov (United States)

Schilling, J; Mueller, R S

2012-07-28

Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.

Comparing the use of Memantine with Dextromethorphan and Placebo to Reduce Pain before Orthopedic Surgery

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Mehrdad Taheri

2017-12-01

Full Text Available Introduction: To compare the use of Memantine with Dextromethorphan and placebo to reduce pain after orthopedic surgery.Materials and Methods: The present study was a double-blind clinical trial including180 patients undergoing elective orthopedic surgery of the lower limbs. Patients were divided randomly into three groups of 60 patients each. The first group (Group M received 30 mg Memantine orally, the second group (Group D received 45 mg of Dextromethorphan and the third group (Group P received only placebo, two and a half hours before the operation. The intensity of pain (VAS score, sedation score, and nausea and vomiting were recorded postoperatively.Results: In this study, 60 patients were enrolled in each group. The total VAS (Visual Analogue Scale score was significantly lower among patients receiving Memantine and the satisfaction was significantly higher compared to the Dextromethorphan and placebo groups (P-value <0.001.Conclusion: The present study results indicate that Memantine has a relatively better outcome compared to Dextromethorphan or placebo in reducing the post surgical pain among patients undergoing orthopedic surgeries. It also reduced the need for post surgical opioid use and improved the patients’ satisfaction.  

The anticonvulsant levetiracetam for the treatment of pain in polyneuropathy: A randomized, placebo-controlled, cross-over trial

DEFF Research Database (Denmark)

Holbech, Jakob Vormstrup; Otto, Marit; Bach, Flemming W

2011-01-01

of this study was to test the analgesic effect of levetiracetam in painful polyneuropathy. METHODS: This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000mg/day versus placebo (6-week treatment periods). Patients with diagnosed polyneuropathy and symptoms for more than......-three patients were screened for participation and 39 patients entered the study. Thirty-five patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.29 versus placebo 2.28, p=0.979), total pain intensity (levetiracetam 5.5 versus placebo 5.3, p=0......Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam. OBJECTIVES: The aim...

A double-blind, randomized, placebo-controlled, fixed-dose phase III study of vilazodone in patients with generalized anxiety disorder.

Science.gov (United States)

Gommoll, Carl; Durgam, Suresh; Mathews, Maju; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Thase, Michael E

2015-06-01

Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 ClinicalTrials.gov) evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (-1.80 [-3.26, -0.34]; P = .0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P = .0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

Clinic Design as Placebo-Using Design to Promote Healing and Support Treatments.

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Rehn, Jonas; Schuster, Kai

2017-11-09

Analogously to the medical placebo effect, people seem to anticipate the quality of treatments based on external stimuli. In order to gain insights on the effect the built environment can have on a person's judgments and behavior with a particular focus on health related issues, a quantitative survey ( N = 851) with four groups before and after the renovation of a rehabilitation clinic has been conducted. In line with an overall modernization of the clinic, the entrance, the lobby, and some patient rooms have been changed. In the lobby, a service counter and coffee bar have been added as well as light colors and new flooring material to achieve a more modern and clean atmosphere in the sense of aesthetical appearance of the space. The outcome revealed that patients rate the intention to change their health behavior as well as the quality of food or significantly higher in a modernized clinic. These differences cannot be directly attributed solely to the changes in the building. Analogously to the medical placebo, an effect referred to as design placebo effect is, therefore, proposed to explain improved ratings of aspects that have not directly been changed due to the intervention. Other significant effects are attributable to winter and summer climate. During summer time, ratings for waiting area, atmosphere, patient rooms, as well as for staff were significantly higher. It is, therefore, assumed that aesthetic attributes, such as architectural design, or friendliness of the weather, exert their effects as perceptual placebos that directly influence judgment outcomes and behavioral intentions. Further research is needed to match certain design and general environmental features to their effects on patients and investigate their effect strength.

A double-blind placebo controlled trial of paroxetine in the ...

African Journals Online (AJOL)

A double-blind placebo controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa. Dan J. Stein, Michael Berk, Charl Els, Robin A. Emsley, Leon Gittelson, Don Wilson, Rosemary Oakes, Brian Hunter ...

Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups

DEFF Research Database (Denmark)

Madsen, Matias Vested; Gøtzsche, Peter C; Hróbjartsson, Asbjørn

2009-01-01

OBJECTIVES: To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect of acupuncture. DESIGN: Systematic review and meta-analysis of three armed randomised clinical trials. DATA SOURCES......: Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT. Data extraction and analysis Standardised mean differences from each trial were used to estimate the effect of acupuncture and placebo acupuncture. The different types of placebo acupuncture were ranked from 1 to 5 according...... to assessment of the possibility of a physiological effect, and this ranking was meta-regressed with the effect of acupuncture. DATA SYNTHESIS: Thirteen trials (3025 patients) involving a variety of pain conditions were eligible. The allocation of patients was adequately concealed in eight trials...

Effectiveness of tamsulosin in prevention of post-operative urinary retention: a randomized double-blind placebo-controlled study

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Ali Hamidi Madani

2014-01-01

Full Text Available Purpose: Urinary retention is one of the most common complications contributing to surgical procedures. Recent studies have shown the benefits of alpha-adrenergic blockers in preventing post-operative urinary retention (POUR. The aim of this prospective study was to compare the prophylactic effect of tamsulosin with placebo on postoperative urinary retention. Materials and Methods: In this randomized placebo controlled, clinical trial, 232 male patients aged 18 to 50 years old admitted to Razi University Hospital for varicocelectomy, inguinal herniorrhaphy, and scrotal surgery were randomly assigned to receive either three doses of 0.4mg tamsulosin (n = 118 or placebo (n = 114, 14 and 2 hours before, and 10 hours after surgery. Patients were closely monitored for the development of urinary retention 24 hours after surgical intervention. The primary endpoint was to investigate the effect of tamsulosin in prevention of post-operative urinary retention during the first 24 hours after surgical intervention. Collected data were analyzed using SPSS software version 18 and the P < 0.05 was considered statistically significant. Results: One hundred and eighteen patients were included in tamsulosin arm and 114 in placebo arm. POUR in patients who received tamsulosin was significantly lower than placebo, as 5.9% of the patients treated with tamsulosin and 21.1% placebo group, reported urinary retention following surgery (P = 0.001. No serious adverse effects were seen in both groups. Conclusions: This study suggests that short perioperative treatment with tamsulosin can reduce the incidence of urinary retention and the need for catheterization after varicocelectomy, inguinal herniorrhaphy, and scrotal surgery.

Botulinum toxin type A-a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study

DEFF Research Database (Denmark)

Petersen, Christina Damsted; Giraldi, Annamaria; Lundvall, Lene

2009-01-01

to receive Botox (N = 32) or saline placebo (N = 32). Botulinum toxin A (20 I.E.) diluted in 0.5 mL saline or 0.5 mL saline was injected in the musculus bulbospongiosus at baseline. MAIN OUTCOME MEASURES: Pain was measured monthly on a visual analog scale (VAS) Likert scale. Sexual function was measured...... pain reduction (P placebo group...... in the vestibule of women diagnosed with vestibulodynia does not reduce pain, improve sexual functioning, or impact the quality of life compared to placebo and evaluated at 3 and 6 moths follow up. Both the Botox group and the placebo groups experienced a reduction in pain on the VAS Likert scale at 6 months...

Natural products for the management of xerostomia: a randomized, double-blinded, placebo-controlled clinical trial.

Science.gov (United States)

Navarro Morante, Anabel; Wolff, Andy; Bautista Mendoza, Gloria Rocio; López-Jornet, Pia

2017-02-01

The aim of this study was to evaluate the clinical performance of lycopene-enriched virgin olive oil in spray form used to treat patients with drug-induced xerostomia, comparing this with a placebo spray. This double-blind, randomized clinical trial included elderly subjects with drug-induced xerostomia (n = 60). Resting salivary flow was measured using the draining technique. The Xerostomia Inventory (XI) was used to assess symptoms and the Oral Health Impact Profile 14 (OHIP-14) to assess patient quality of life. Evaluations were made before and after 12 weeks of product/placebo application. Sixty patients took part in the study. Symptoms improved among the treatment group (n = 30) after 12 weeks in the following XI domains: 'Rate the difficulty you experience in speaking because of dryness' (P = 0.03); 'Rate how much saliva is in your mouth' (P = 0.03); and 'Rate the dryness of your lips' (P = 0.04). The placebo group (n = 30) underwent improvements in: 'Rate how much saliva is in your mouth' (P = 0.02) and 'Rate the dryness of your mouth' (P = 0.01). A significant improvement (P = 0.001) in oral-related quality of life (OHIP-14) was identified in the treatment group, while no significant differences were observed in the placebo group (P > 0.05). The topical application of lycopene-enriched virgin olive oil and its placebo counterpart improved xerostomia-related symptoms significantly (but not salivary flow rate) in patients with drug-induced xerostomia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Indoramin pregnancy in the treatment hypertension of A placebo ...

African Journals Online (AJOL)

A placebo-controlled trial was used to assess the antihypertensive efficacy of indoramin in the management of pregnancy hypertension. Sixty patients were recruited into the study and only 17 attained satisfactory blood pressure control. In the doses of drugs administered indoramin was not shown to be more effective than ...

Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

2017-02-01

Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

The effect of montelukast on early-life wheezing: A randomized, double-blinded placebo-controlled study.

Science.gov (United States)

Keskin, Ozlem; Arik Yilmaz, Ebru; Motzkus, Christine; Sackesen, Cansin; Lilly, Craig M; Kalayci, Omer

2018-02-01

Cysteinyl-leukotrienes are increased in the airways of infants with virus-associated wheezing. We aimed to determine the effects of a cysteinyl-leukotriene-1 receptor antagonist on symptoms during an early-life wheezing illness and to investigate the factors that affect the response to this drug. This placebo-controlled double-blinded randomized controlled trial recruited children aged 3-36 months with wheezing illness and randomized to active drug or placebo for 56 days. A symptom score diary (SSD) was kept by the children's caregivers. One-hundred patients completed the study, and 62 (30 montelukast and 32 placebo) were analyzed. There were no significant differences in the percent of symptom-free days, symptom scores, and the need for rescue salbutamol between the two groups. However, the percent of symptom-free days within the first week was significantly higher for the montelukast than for the placebo group (13.8 ± 4.1% vs. 5.4 ± 3.4%; P = 0.028); wheezing score at 7th day was significantly lower for the montelukast than for the placebo group (0.5 ± 0.1 vs. 1.4 ± 0.2; P = 0.002). In addition, the number of inhaled ß 2 -agonist rescue episodes per day during the first week was significantly lower for the montelukast compared with the placebo group (12.7 ± 1.8 vs. 19.2 ± 1.6; P = 0.013). Conclusions Our results indicate that montelukast may be effective for reducing caregiver-observed wheezing and the need for salbutamol during the first week of treatment for early-life wheezing. The impact for caregivers and the optimal duration of treatment will need to be explored in studies of larger size. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.

Science.gov (United States)

Limsrivilai, Julajak; Charatcharoenwitthaya, Phunchai; Pausawasdi, Nonthalee; Leelakusolvong, Somchai

2016-02-01

Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.

Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial.

Science.gov (United States)

Ehrhardt, Stephan; Guo, Nan; Hinz, Rebecca; Schoppen, Stefanie; May, Jürgen; Reiser, Markus; Schroeder, Maximilian Philipp; Schmiedel, Stefan; Keuchel, Martin; Reisinger, Emil C; Langeheinecke, Andreas; de Weerth, Andreas; Schuchmann, Marcus; Schaberg, Tom; Ligges, Sandra; Eveslage, Maria; Hagen, Ralf M; Burchard, Gerd D; Lohse, Ansgar W

2016-01-01

Background.  Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Data on the efficacy of probiotics to prevent AAD and CDAD are unclear. We aimed to evaluate the efficacy of Saccharomyces boulardii to prevent AAD and CDAD in hospitalized adult patients. Methods.  We conducted a multicenter, phase III, double-masked, randomized, placebo-controlled trial in hospitalized patients who received systemic antibiotic treatment in 15 hospitals in Germany between July 2010 and October 2012. Participants received Perenterol forte 250 mg capsules or matching placebo twice per day within 24 hours of initiating antibiotic treatment, continued treatment for 7 days after antibiotic discontinuation, and were then observed for 6 weeks. Results.  Two thousand four hundred forty-four patients were screened. The trial was stopped early for futility after inclusion of 477 participants. Two hundred forty-six patients aged 60.1 ± 16.5 years and 231 patients aged 56.5 ± 17.8 were randomized to the S boulardii group and the placebo group, respectively, with 21 and 19 AADs in the respective groups (P = .87). The hazard ratio of AAD in the S boulardii group compared with the placebo group was 1.02 (95% confidence interval, .55-1.90; P = .94). Clostridium difficile-associated diarrhea occurred in 0.8% of participants (4 of 477). Nine serious adverse events were recorded in the S boulardii group, and 3 serious adverse events were recorded in the placebo group. None were related to study participation. Conclusions.  We found no evidence for an effect of S boulardii in preventing AAD or CDAD in a population of hospitalized patients without particular risk factors apart from systemic antibiotic treatment. ClinicalTrials.gov Identifier.  NCT01143272.

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study.

Science.gov (United States)

Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

2007-11-01

To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Randomised, double blind, placebo controlled crossover trial, with two 2-week treatment periods separated by a 2-week placebo washout. Six UK paediatric departments. 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting > or =3 months), defined as or =25% of bowel movements with straining; > or =25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; pPEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (pPEG+E (41%) and placebo during treatment (45%). PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016.

Directory of Open Access Journals (Sweden)

Arif Khan

Full Text Available Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension.For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms. Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures.Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018 and effect size (R2 = 0.013, p = 0.187 drug-placebo difference (R2 = 0.013, p = 0.182 and success rate (134/142, 94.4% have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001. Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001 and stable, large effect sizes (0.78 ±0.37. The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877, antihypertensive-placebo differences (p = 0.752, or p-values (p = 0.963 but was correlated with antihypertensive response

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

Science.gov (United States)

Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, parms are likely overpowered with sample sizes increasing over time (R2 = 0.387, pblood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical

Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory.

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Mednick, Sara C; Cai, Denise J; Kanady, Jennifer; Drummond, Sean P A

2008-11-03

Caffeine, the world's most common psychoactive substance, is used by approximately 90% of North Americans everyday. Little is known, however, about its benefits for memory. Napping has been shown to increase alertness and promote learning on some memory tasks. We directly compared caffeine (200mg) with napping (60-90min) and placebo on three distinct memory processes: declarative verbal memory, procedural motor skills, and perceptual learning. In the verbal task, recall and recognition for unassociated words were tested after a 7h retention period (with a between-session nap or drug intervention). A second, different, word list was administered post-intervention and memory was tested after a 20min retention period. The non-declarative tasks (finger tapping task (FTT) and texture discrimination task (TDT)) were trained before the intervention and then retested afterwards. Naps enhanced recall of words after a 7h and 20min retention interval relative to both caffeine and placebo. Caffeine significantly impaired motor learning compared to placebo and naps. Napping produced robust perceptual learning compared with placebo; however, naps and caffeine were not significantly different. These findings provide evidence of the limited benefits of caffeine for memory improvement compared with napping. We hypothesize that impairment from caffeine may be restricted to tasks that contain explicit information; whereas strictly implicit learning is less compromised.

Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

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Sánchez-de la Osa Reinaldo B

2008-02-01

Full Text Available Abstract Background High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC. Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. Results Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%. At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before, with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated

Varenicline for opioid withdrawal in patients with chronic pain: a randomized, single-blinded, placebo controlled pilot trial.

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Hooten, W Michael; Warner, David O

2015-03-01

The objectives of this randomized, single-blinded, placebo-controlled pilot trial were to investigate the effects of varenicline on opioid withdrawal among chronic pain patients undergoing opioid detoxification in an interdisciplinary pain program and the feasibility of varenicline use in this population. Twenty-one patients were recruited (varenicline=10, placebo=11), and 7 patients in the varenicline and 11 in the placebo group completed the study. Opioid withdrawal was quantified using the Clinical Opiate Withdrawal Scale, and varenicline-related adverse effects were assessed. Opioid withdrawal scores tended to decrease over the course of opioid tapering in those receiving varenicline and increase in those receiving placebo. Varenicline was well-tolerated in this population, with no adverse drug effects (including nausea) observed and no effect on improvements in pain severity and depression. This randomized pilot study provides preliminary data for future trials of varenicline in opioid-dependent adults with chronic pain undergoing medically directed opioid detoxification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

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Stéphanie J.E. Becker

2014-09-01

 Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial. 

A comparison of placebo response with major depressive disorder in patients recruited through newspaper advertising versus consultation referrals.

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Miller, C A; Hooper, C L; Bakish, D

1997-01-01

Recent evidence indicates few differences between patients recruited through advertising and by consultation referral, and there is some suggestion that those recruited through advertising are more representative of the target community population. However little has been reported on differences in placebo response and compliance in these two patient groups. We conducted a retrospective chart review of 49 patients with major depressive disorder (MDD), recruited through advertising or consultation, randomized to placebo in five clinical trials. Variables included demographics, clinical history, efficacy, compliance, and completion data. Homogeneity was demonstrated for most variables. Differences in placebo groups included significantly lower Hamilton Rating Scale for Depression (HAM-D) scores for the advertisement group throughout the trials. Advertisement patients were also more likely to be early placebo responders and in remission at Days 14 and 28. No differences were found in completion rates or reasons for early termination. Compliance was excellent for both groups. Early placebo response of the advertisement group reinforces the need for trials of at least 8 weeks. In addition, consultation patients may have a more severe illness and be treatment resistant, suggesting they are less generalizable to community practice populations.

Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

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Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

2016-01-01

Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study.

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Bruyère, O; Zegels, B; Leonori, L; Rabenda, V; Janssen, A; Bourges, C; Reginster, J-Y

2012-06-01

Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months, in subjects with joint pain at the lower or upper limbs or at the lumbar spine. Comparative double-blind randomized multicenter study in parallel groups. 200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale (VAS). Collagen hydrolysate 1200 mg/day or placebo during 6 months. Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study. A responder subject was defined as a subject experiencing a clinically significant improvement (i.e. by 20% or more) in the most painful joint using the VAS score. All analyses were performed using an intent-to-treat procedure. At 6 months, the proportion of clinical responders to the treatment, according to VAS scores, was significantly higher in the collagen hydrolysate (CH) group 51.6%, compared to the placebo group 36.5% (pvs. 39.6%, p=0.53). No significant difference in terms of security and tolerability was observed between the two groups. This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo. More studies are needed to confirm the clinical interest of this food supplement. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

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Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Predictors of placebo response in adults with attention-deficit/hyperactivity disorder: data from 2 randomized trials of osmotic-release oral system methylphenidate

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Buitelaar, J.K.; Sobanski, E.; Stieglitz, R.D.; Dejonckheere, J.; Waechter, S.; Schauble, B.

2012-01-01

OBJECTIVE: To find potential correlates of placebo response in adults with attention-deficit/hyperactivity disorder (ADHD) and gain insights into why placebo response may be high in clinical trials. METHOD: Post hoc analysis of placebo data from 2 randomized controlled trials of osmotic-release oral

Placebo response in neuropathic pain after spinal cord injury: a meta-analysis of individual participant data

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Jutzeler CR

2018-04-01

Full Text Available Catherine R Jutzeler,1–3 Freda M Warner,1,2 Jacquelyn J Cragg,1,3 Jenny Haefeli,4 J Scott Richards,5 Sven R Andresen,6 Nanna B Finnerup,7,8 Catherine Mercier,9 John LK Kramer1,2 1Faculty of Medicine, ICORD, University of British Columbia, Vancouver, BC, Canada; 2Faculty of Education, School of Kinesiology, University of BC, Vancouver, BC, Canada; 3Faculty of Medicine, Spinal Cord Injury Center, University Hospital Balgrist, University of Zurich, Zurich, Switzerland; 4Weill Institute for Neurosciences, Department of Neurological Surgery, Brain and Spinal Injury Center, University of California, San Francisco, CA, USA; 5Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA; 6Spinal Cord Injury Centre of Western Denmark, Department of Neurology, Regional Hospital of Viborg, Viborg, Denmark; 7Danish Pain Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 8Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 9Center for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC, Canada Background: Understanding factors associated with high placebo responses in clinical trials increases the likelihood of detecting a meaningful treatment effect. The aim of the present study was to identify subject-level factors that contribute to placebo variability in patients with neuropathic pain due to spinal cord injury (SCI.Methods: Multiple regression analysis of patient data from randomized, double-blind, placebo-controlled trials (duration >4 weeks involving individuals with SCI was performed. Patient demographics, as well as injury and pain characteristics were examined for their association with changes in pain rating from baseline to the end of the trial (i.e., placebo response. The overall effect of individual predictors was quantified with meta-analysis statistics.Results: A total of 276 patients with SCI from six studies were

Rates of cognitive change in Alzheimer disease: Observations across a decade of placebo-controlled clinical trials with donepezil

DEFF Research Database (Denmark)

Jones, Roy W; Schwam, Elias; Wilkinson, David

2009-01-01

Treatment success in Alzheimer disease (AD) trials is generally based on benefits over placebo-treated controls. Consequently, variation in rates of decline among placebo-treated patients could impact outcomes from AD trials. In the present analyses, individual patient data [baseline Mini......-Mental State Examination (MMSE): 10 to 26] were pooled from randomized, placebo-controlled studies of donepezil for AD conducted during the 1990s, and grouped by initiation year-group 1: 1990 to 1994; group 2: 1996 to 1999. Changes in MMSE and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS...

Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

NARCIS (Netherlands)

de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

Comparison of Intravenous Morphine Versus Paracetamol in Sciatica: A Randomized Placebo Controlled Trial.

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Serinken, Mustafa; Eken, Cenker; Gungor, Faruk; Emet, Mucahit; Al, Behcet

2016-06-01

The objective was to compare intravenous morphine and intravenous acetaminophen (paracetamol) for pain treatment in patients presenting to the emergency department with sciatica. Patients, between the ages of 21 and 65 years, suffering from pain in the sciatic nerve distribution and a positive straight leg-raise test composed the study population. Study patients were assigned to one of three intravenous interventions: morphine (0.1 mg/kg), acetaminophen (1 g), or placebo. Physicians, nurses, and patients were blinded to the study drug. Changes in pain intensity were measured at 15 and 30 minutes using a visual analog scale. Rescue drug (fentanyl) use and adverse effects were also recorded. Three-hundred patients were randomized. The median change in pain intensity between treatment arms at 30 minutes were as follows: morphine versus acetaminophen 25 mm (95% confidence interval [CI] = 20 to 29 mm), morphine versus placebo 41 mm (95% CI = 37 to 45 mm), and acetaminophen versus placebo 16 mm (95% CI = 12 to 20 mm). Eighty percent of the patients in the placebo group (95% CI = 63.0% to 99%), 18% of the patients in the acetaminophen group (95% CI = 10.7% to 28.5%), and 6% of those in the morphine group (95% CI = 2.0% to 13.2%) required a rescue drug. Adverse effects were similar between the morphine and acetaminophen groups. Morphine and acetaminophen are both effective for treating sciatica at 30 minutes. However, morphine is superior to acetaminophen. © 2016 by the Society for Academic Emergency Medicine.

Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

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Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

2017-12-01

To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P gout flares (29.3% versus 41.4%; P gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial.

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Bloch, Michael H; Panza, Kaitlyn E; Yaffa, Alisa; Alvarenga, Pedro G; Jakubovski, Ewgeni; Mulqueen, Jilian M; Landeros-Weisenberger, Angeli; Leckman, James F

2016-05-01

Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study. Thirty-one children and adolescents 8-17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo. Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes. We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.

Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

Science.gov (United States)

Ball, M Patricia; Warren, Kimberly R; Feldman, Stephanie; McMahon, Robert P; Kelly, Deanna L; Buchanan, Robert W

2011-04-01

In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

Science.gov (United States)

Pecknold, J; Luthe, L; Munjack, D; Alexander, P

1994-10-01

This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

The Effect of Prior Caffeine Consumption on Neuropsychological Test Performance: A Placebo-Controlled Study.

Science.gov (United States)

Walters, Elizabeth R; Lesk, Valerie E

2016-01-01

The aim of this study was to investigate whether the prior consumption of 200 mg of pure caffeine affected neuropsychological test scores in a group of elderly participants aged over 60 years. Using a double-blind placebo versus caffeine design, participants were randomly assigned to receive 200 mg of caffeine or placebo. A neuropsychological assessment testing the domains of general cognitive function, processing speed, semantic memory, episodic memory, executive function, working memory and short-term memory was carried out. Significant interaction effects between age, caffeine and scores of executive function and processing speed were found; participants who had received caffeine showed a decline in performance with increasing age. This effect was not seen for participants who received placebo. The results highlight the need to consider and control prior caffeine consumption when scoring neuropsychological assessments in the elderly, which is important for accuracy of diagnosis and corresponding normative data. © 2016 S. Karger AG, Basel.

Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

Science.gov (United States)

Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

2016-09-01

α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

Prediction of placebo responses: A systematic review of the literature

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Bjoern eHoring

2014-10-01

Full Text Available Objective: Predicting who responds to placebo treatment – and under which circumstances – has been a question of interest and investigation for generations. However, the literature is disparate and inconclusive. This review aims to identify publications that provide high quality data on the topic of placebo response (PR prediction. Methods: To identify studies concerned with PR prediction, independent searches were performed in an expert database (for all symptom modalities and in PubMed (for pain only. Articles were selected when a they assessed putative predictors prior to placebo treatment and b an adequate control group was included when the association of predictors and PRs were analyzed. Results: Twenty-one studies were identified, most with pain as dependent variable. Most predictors of PRs were psychological constructs related to actions, expected outcomes and the emotional valence attached to these events (goal-seeking, self-efficacy/-esteem, locus of control, optimism. Other predictors involved behavioural control (desire for control, eating restraint, personality variables (fun seeking, sensation seeking, neuroticism, biological markers (sex, a single nucleotide polymorphism related to dopamine metabolism. Finally, suggestibility and beliefs in expectation biases, body consciousness and baseline symptom severity were found to be predictive. Conclusions: While results are heterogeneous, some congruence of predictors can be identified. PRs mainly appear to be moderated by expectations of how the symptom might change after treatment, or the expectation of how symptom repetition can be coped with. It is suggested to include the listed constructs in future research. Furthermore, a closer look at variables moderating symptom change in control groups seems warranted.

Placebo and the new physiology of the doctor-patient relationship.

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Benedetti, Fabrizio

2013-07-01

Modern medicine has progressed in parallel with the advancement of biochemistry, anatomy, and physiology. By using the tools of modern medicine, the physician today can treat and prevent a number of diseases through pharmacology, genetics, and physical interventions. Besides this materia medica, the patient's mind, cognitions, and emotions play a central part as well in any therapeutic outcome, as investigated by disciplines such as psychoneuroendocrinoimmunology. This review describes recent findings that give scientific evidence to the old tenet that patients must be both cured and cared for. In fact, we are today in a good position to investigate complex psychological factors, like placebo effects and the doctor-patient relationship, by using a physiological and neuroscientific approach. These intricate psychological factors can be approached through biochemistry, anatomy, and physiology, thus eliminating the old dichotomy between biology and psychology. This is both a biomedical and a philosophical enterprise that is changing the way we approach and interpret medicine and human biology. In the first case, curing the disease only is not sufficient, and care of the patient is of tantamount importance. In the second case, the philosophical debate about the mind-body interaction can find some important answers in the study of placebo effects. Therefore, maybe paradoxically, the placebo effect and the doctor-patient relationship can be approached by using the same biochemical, cellular and physiological tools of the materia medica, which represents an epochal transition from general concepts such as suggestibility and power of mind to a true physiology of the doctor-patient interaction.

A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications.

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DiPalma, Jack A; Cleveland, Mark B; McGowan, John; Herrera, Jorge L

2007-11-01

Medications often cause constipation and little data are available concerning treatment interventions. This study was designed to evaluate the safety and efficacy of polyethylene glycol (PEG) 3350 laxative (MiraLax) for relief of constipation from medicines associated with symptoms of constipation. Study subjects were enrolled who met defined criteria for chronic constipation and were also taking medications that were associated with a reported side effect incidence of more than 3% constipation. Subjects were randomized into a double-blind, parallel, multicenter study where they received 17 g per day of PEG laxative or placebo for 28 days. The primary efficacy variable, "Treatment Success," was defined as relief of ROME II criteria for constipation over the last 7 days of the treatment period. Various secondary measures were also assessed. Daily bowel movement experience, patient perception of efficacy, and safety information were recorded in a diary. Laboratory testing was performed at baseline and at end of study for hematology and blood chemistry, including BUN, calcium, electrolytes, and TSH. One hundred patients were enrolled at 4 study centers. Successful treatment according to the primary efficacy variable was seen in 78.3% of PEG and 39.1% of placebo subjects (P PEG compared with placebo (P PEG and placebo. No significant differences in laboratory findings or adverse events, including the gastrointestinal category, were observed. Diarrhea and flatulence occurred more frequently with PEG treatment, although they were not individually statistically different from placebo. Similar results were observed when these symptoms were analyzed for differences due to gender, race, or age. PEG laxative is safe and effective for use in treating constipation in patients taking constipating medications.

Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study.

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Guarda-Nardini, Luca; Manfredini, Daniele; Salamone, Milena; Salmaso, Luigi; Tonello, Stefano; Ferronato, Giuseppe

2008-04-01

The present investigation is a preliminary double-blind, controlled placebo, randomized clinical trial with a six month follow-up period. The study aimed to assess the efficacy of type A botulinum toxin (Botox, Allergan, Inc. Irvine, CA) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers. Twenty patients (ten males, ten females; age range 25-45) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind, controlled placebo, randomized clinical trial, with a treatment group (ten subjects treated with botulinum toxin injections- BTX-A) and a control group (ten subjects treated with saline placebo injections). A number of objective and subjective clinical parameters (pain at rest and during chewing; mastication efficiency; maximum nonassisted and assisted mouth opening, protrusive and laterotrusive movements; functional limitation during usual jaw movements; subjective efficacy of the treatment; tolerance of the treatment) were assessed at baseline time and at one week, one month, and six months follow-up appointments. Descriptive analysis showed that improvements in both objective (range of mandibular movements) and subjective (pain at rest; pain during chewing) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects. Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects. Differences were not significant in some cases due to the small sample size. Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and provided pilot data which need to be confirmed by further research using larger samples.

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

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Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

2015-01-01

Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

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Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K

2005-01-01

Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability. PMID:15897310

Fluoxetine increases suicide ideation less than placebo during treatment of adults with minor depressive disorder.

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Garlow, Steven J; Kinkead, Becky; Thase, Michael E; Judd, Lewis L; Rush, A John; Yonkers, Kimberly A; Kupfer, David J; Frank, Ellen; Schettler, Pamela J; Rapaport, Mark Hyman

2013-09-01

Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Research subjects were adult outpatients with minor depressive disorder (N = 162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase (p = 0.04). Survival analysis revealed that subjects on placebo were significantly more likely (p = 0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

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Dietlind L. Wahner-Roedler

2011-01-01

Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

Towards Contemporary Neuroethics: Why Does It Make Sense to Re-define Placebo?

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Niko Gorjup

2014-10-01

Full Text Available The main message we are trying to get across throughout the article is that the placebo is not an inert entity but instead it has a potential of subjective interpretation, a healing potential of its own, over and above that of any healing potential of the medication per se. Such healing potential is greatly dependent on how strong the interpretation value in being healed is that is created by the doctor. In this regard, we are also arguing that there are myriads possibilities at work that can influence how strong this interpretation value can become. The crucial role of contemporary medicine should be to expand the use of these interpretation effects even more and use them to help reduce any negative mental states that could continue to suppress the immune system after the initial healing. In other words, medicine should use the power of interpretation effect not only to re-arouse the immune system temporarily but permanently. In order to achieve a complete process of permanent healing it is necessary to take advantage of making full use of the powerful interpretation value through psychosocial context. It is possible to do that beyond the usual “sugar pill” through evidence based approach – a science of compassionate care! By introducing the new operational placebo definitions, we clearly show that the human mind (unconscious and conscious is an inevitable substance involved in the Healing Process. The terms “placebo”, “placebo effect”, and “placebo response” are re-defined into the new working definitions. We explain how there is no more distinction (duality such as body / mind, specific / nonspecific or health / disease, which offers new insights for future directions in contemporary Neuroethics.

Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial.

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Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

2012-01-01

It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. In a randomized double-blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8(th) and 12(th) weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity.

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

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Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

2010-01-01

This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia.

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Schabus, Manuel; Griessenberger, Hermann; Gnjezda, Maria-Teresa; Heib, Dominik P J; Wislowska, Malgorzata; Hoedlmoser, Kerstin

2017-04-01

See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article.Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the 'law of effect'. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 12-15 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral electroencephalographic

A Phase 3 Placebo-Controlled, Double Blind, Multi-Site Trial of the alpha-2-adrenergic Agonist, Lofexidine, for Opioid Withdrawal

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Yu, Elmer; Miotto, Karen; Akerele, Evaristo; Montgomery, Ann; Elkashef, Ahmed; Walsh, Robert; Montoya, Ivan; Fischman, Marian W.; Collins, Joseph; McSherry, Frances; Boardman, Kathy; Davies, David K.; O’Brien, Charles P.; Ling, Walter; Kleber, Herbert; Herman, Barbara H.

2008-01-01

Context Lofexidine is an alpha-2-A noradrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally-defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. Design An inpatient, Phase 3, placebo-controlled, double blind, randomized multi-site trial with three phases: (1) Opioid Agonist Stabilization Phase (days 1–3), (2) Detoxification/Medication or Placebo Phase (days 4–8), and (3) Post Detoxification/Medication Phase (days 9–11). Subjects Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main Outcome Measure Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (2nd opioid detoxification treatment day). Results Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (Least squares means 19.5 ± 2.1 versus 30.9 ± 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Trial Registration trial registry name A Phase 3 Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal, registration number NCT00032942, URL for the registry http://clinicaltrials.gov/ct/show/NCT00032942?order=4. PMID:18508207

Autologous Conditioned Plasma Versus Placebo Injection Therapy in Lateral Epicondylitis of the Elbow: A Double Blind, Randomized Study.

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Schöffl, Volker; Willauschus, Wolfgang; Sauer, Felix; Küpper, Thomas; Schöffl, Isabelle; Lutter, Christoph; Gelse, Kolja; Dickschas, Jörg

2017-01-01

Introduction  There are various therapeutic approaches to the treatment of lateral epicondylitis, a highly prevalent musculoskeletal disorder. Recently, injection therapy with autologous conditioned plasma (ACP) has shown promise as a new approach. Methods  Set up as a prospective, double-blind, randomized controlled clinical trial, this study involved 50 patients with lateral epicondylitis. Following external randomization, 25 patients received one round of injection therapy with ACP (platelet rich plasma, PRP), while the remaining 25 patients received a placebo of 0.9 % NaCl. All patients were re-evaluated with respect to lateral epicondylitis of the elbow at four-weeks and six-months post-injection. Results  Out of 50 patients, 36 qualified for reevaluation, 18 patients from the ACP therapy group and 18 from the placebo group. The initial Disability of the Arm, Shoulder and Hand (DASH) score for all reevaluated patients was 36.4 in the ACP group, and 41.0 in the placebo group; both groups exhibited decreased DASH scores at the four-week and six-month post-injection follow-up (6 months: ACP 30.1, placebo 25.8). The decrease of the DASH score after 4 weeks was greater and qualified as statistically significant in the placebo group (p = 0.041), compared to the DASH score decrease in the ACP treatment group, which was statistically non-significant. Additionally, the difference between the DASH scores of the treatment and placebo groups was statistically non-significant four weeks and six months after treatment. Discussion  The results of this study suggest a therapeutic effect in both the ACP and placebo groups, with no evidence for a therapeutically significant difference between ACP and placebo treatments. It is hypothesized that, in accordance with the study protocols, injection with a local anaesthetic prior to ACP therapy may have an influence on the therapeutic effect of ACP. Future studies have to confirm recent findings that demonstrated a

Efecto placebo en el tratamiento conductual del insomnio : un enfoque desde las diferencias individuales

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Aluja Fabregat, Antón; Farré Martí, Josep Ma.

1986-01-01

En el trabajo que se presenta se revisan varias investigaciones sobre el tratamiento conductual del insomnio de conciliación en los que se utilizan procedimientos de control placebo. Se encuentra que los procedimientos diseñados como control placebo causan diferentes efectos sobre la disminución de la latencia inicial de sueño, por lo que se infiere que por su naturaleza los distintos procedimientos diseñados inciden inespecíficamente en los sujetos insomnes.Se intenta buscar analogías hipoté...

Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo

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Baldwin, David S.; Asakura, Satoshi; Koyama, Tsukasa; Hayano, Taiji; Hagino, Atsushi; Reines, Elin; Larsen, Klaus

2016-01-01

Escitalopram is the most selective of the serotonin reuptake inhibitor (SSRI) antidepressants. We conducted a meta-analysis of placebo-controlled studies where escitalopram was used to treat patients with social anxiety disorder (SAD). Data from all randomised, double-blind placebo-controlled studies in SAD with escitalopram from both specialist settings and general practice were used. Patients met the DSM-IV criteria for SAD, ?18 years old, Liebowitz Social Anxiety Scale (LSAS) ?60. The prim...

Mastalgia cíclica pré-menstrual: placebo versus outras drogas Pre-menstrual cyclic mastalgia

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Laurival A. De Luca

2006-08-01

Full Text Available Os autores definem mastalgia cíclica pré-menstrual, (MCPM, repassam os principais mecanismos do ciclo celular da mama, e com base nestes conhecimentos propõem a sua classificação em três tipos, segundo a fisiologia do ciclo mamário: tipo 1 - caracterizado pela distensão localizada de ductos e adensamento do tecido conjuntivo em volta de pequenas dilatações. tipo II - caracterizado pelo edema intersticial, e tipo III - caracterizado pela combinação dos dois processos etiopatogênicos. OBJETIVO: Por meio de estudo prospectivo, aleatório, triplo cego e controlado, comparar a ação de placebo com associação de vitaminas A-D-E e doses baixas de ácido acetilsalicílico. MÉTODOS: Foram observadas 259 portadoras de MCPM, acompanhadas durante seis meses para estudo comparativo das drogas empregadas no alívio da dor. Destas, foram selecionadas 81 pacientes por critérios rigorosos, divididas em três grupos de 27, que receberam, respectivamente, aspirina, associação de vitaminas e placebo. A dor foi classificada em grau I (sem dor, grau II (dor moderada e grau III (dor intensa. Os métodos estatísticos realizados mostraram que o número de pacientes em cada grupo era satisfatório. Foi empregado o teste de Tukey para comparação dos resultados e significância a 5%. RESULTADOS: As características clínicas, idade, peso, altura e IMC, antecedentes obstétricos e duração da amamentação foram semelhantes nos três grupos. Houve redução de intensidade da dor nos três grupos, principalmente naquele que recebeu placebo. CONCLUSÃO: O estudo realizado, segundo metodologia aceitável, porque foi prospectivo, controlado, triplo cego e aleatório, não mostrou diferenças significativas no tratamento da mastalgia cíclica pré-menstrual entre aspirina e associação de vitaminas, mas revelou superioridade do placebo.OBJECTIVES: To compare therapeutic effects of placebo with intake of low doses of acetyl-salysilic acid (aspirin and a

Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients.

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Liu, Jixin; Ma, Shaohui; Mu, Junya; Chen, Tao; Xu, Qing; Dun, Wanghuan; Tian, Jie; Zhang, Ming

2017-10-01

Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A take-home placebo treatment can reduce stress, anxiety and symptoms of depression in a non-patient population.

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Darragh, Margot; Yow, Boris; Kieser, Anel; Booth, Roger J; Kydd, Robert R; Consedine, Nathan S

2016-09-01

With a healthcare system burdened by symptomatic and mental-health related conditions, the placebo effect may represent a useful clinical tool. First, however, there is a need to broaden research attention and investigate placebo effects outside laboratories and beyond experimental pain. This study investigated the effectiveness of a take-home placebo treatment in the short-term alleviation of stress, anxiety and symptoms of depression in a non-patient population. A sample of 77 participants was randomized to either the 'oxytocin' treatment group (n = 22), the 'serotonin' treatment group (n = 22) or the wait-list control group (n = 33). The two treatment groups were given an 'anti-stress treatment spray' (placebo) to self-administer for 3 days, and completed online measures of perceived stress (Perceived Stress Scale-10), anxiety (Cognitive Somatic Anxiety Questionnaire) and symptoms of depression (Centre for Epidemiological Studies - Depression) before and after the 3-day protocol. Both the 'serotonin' and 'oxytocin' treatment sprays were effective in reducing symptoms of depression; however, only those in the 'oxytocin' group reported less stress and anxiety as compared with controls. Overall, the 'oxytocin' was perceived as more effective. Placebo effects can be translated to a real-life setting in the short-term reduction of stress, anxiety and symptoms of depression in a non-patient population. In treating psychological distress, placebos may be useful addition to the treatment repertoire. The information given with treatment may also be an important consideration for practitioners. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.

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Pozzoni, Pietro; Riva, Alessia; Bellatorre, Alessandro Giacco; Amigoni, Maria; Redaelli, Elena; Ronchetti, Anna; Stefani, Mariangela; Tironi, Rosangela; Molteni, Edoardo Ennio; Conte, Dario; Casazza, Giovanni; Colli, Agostino

2012-06-01

Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

Moderators of smoking cessation outcomes in a randomized-controlled trial of varenicline versus placebo.

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Littlewood, Rae A; Claus, Eric D; Wilcox, Claire E; Mickey, Jessica; Arenella, Pamela B; Bryan, Angela D; Hutchison, Kent E

2017-12-01

Varenicline has gained a reputation as the optimal intervention for treatment resistant smokers, yet more than half of those who try it do not succeed. To better understand individual differences in the effectiveness of varenicline, this study evaluates the effectiveness of varenicline for smoking cessation in a double-blind, placebo-controlled, randomized clinical trial and examines the influence of psychological factors on treatment outcome. Two hundred five cigarette smokers interested in quitting were randomly assigned to 12 weeks of varenicline or placebo. Outcomes examined were CO-confirmed continuous abstinence for the past month, average number of cigarettes smoked per day, and 7-day point prevalence. Varenicline-treated participants were more likely than placebo to achieve continuous abstinence at the end of treatment (OR = 3.29; RR = 2.62), and 7-day point prevalence rates showed an effect of medication at each time point. Participants in both groups significantly reduced their smoking during the course of treatment and follow-up, and the medication by visit interaction was significant in the expected direction. Impulsivity and personality style emerged as moderators of the relationship between medication condition and treatment outcome. In addition to replicating efficacy results for varenicline versus placebo, the present study shows that the efficacy of pharmacotherapy is influenced by psychological factors. In an era where pharmacotherapy is often perceived as the "silver bullet," we are reminded that smoking cessation is a dynamic process and intervention must be adaptable to address individual differences.

Radon balneotherapy and physical activity for osteoporosis prevention: a randomized, placebo-controlled intervention study.

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Winklmayr, Martina; Kluge, Christian; Winklmayr, Wolfgang; Küchenhoff, Helmut; Steiner, Martina; Ritter, Markus; Hartl, Arnulf

2015-03-01

Low-dose radon hyperthermia balneo treatment (LDRnHBT) is applied as a traditional measure in the non-pharmacological treatment of rheumatic diseases in Europe. During the last decades, the main approach of LDRnHBT was focused on the treatment of musculoskeletal disorders, but scientific evidence for the biological background of LDRnHBT is weak. Recently, evidence emerged that LDRnHBT influences bone metabolism. We investigated, whether combined LDRnHBT and exercise treatment has an impact on bone metabolism and quality of life in a study population in an age group at risk for developing osteoporosis. This randomized, double-blind, placebo-controlled trial comprised guided hiking tours and hyperthermia treatment in either radon thermal water (LDRnHBT) or radon-free thermal water (PlaceboHBT). Markers of bone metabolism, quality of life and somatic complaints were evaluated. Statistics was performed by linear regression and a linear mixed model analysis. Significant changes over time were observed for most analytes investigated as well as an improvement in self-assessed health in both groups. No significant impact from the LDRnHBT could be observed. After 6 months, the LDRnHBT group showed a slightly stronger reduction of the osteoclast stimulating protein receptor activator of nuclear kB-ligand compared to the PlaceboHBT group, indicating a possible trend. A combined hyperthermia balneo and exercise treatment has significant immediate and long-term effects on regulators of bone metabolism as well as somatic complaints. LDRnHBT and placeboHBT yielded statistically equal outcomes.

Sucralfate or placebo following argon plasma coagulation for chronic radiation proctitis: a randomized double blind trial.

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Chruscielewska-Kiliszek, M R; Regula, J; Polkowski, M; Rupinski, M; Kraszewska, E; Pachlewski, J; Czaczkowska-Kurek, E; Butruk, E

2013-01-01

Chronic radiation proctitis is a long-term complication of radiation therapy for pelvic malignancy. The aim of this study was to compare the efficacy and safety of two treatment regimens, sucralfate or placebo, following argon plasma coagulation (APC) for chronic haemorrhagic radiation proctitis. A single-centre, randomized, placebo-controlled, double-blind study was performed on patients with haemorrhagic chronic radiation proctitis after irradiation for prostate, uterine, cervical, rectal or vaginal cancer. All patients received APC, and were then randomized to oral sucralfate (6 g twice a day) or placebo treatment for 4 weeks. APC was repeated every 8 weeks if necessary after the first session. Patients were graded clinically and endoscopically according to the Chutkan and Gilinski scales before and at 8 and 16 weeks after initial APC treatment (1.5-2 l/min, 25-40 W) and after 52 weeks (clinical only). Of 122 patients, 117 completed the entire protocol, with 57/60 in the sucralfate group and 60/62 in the placebo group. At baseline there were no significant differences between the sucralfate and placebo groups. At 1 year, a significant improvement in the clinical scale in both groups occurred compared with baseline. After 16 weeks, the median overall clinical severity scores fell from 4 to 2 points and the median bleeding score from 2 to 0 in both groups. APC is safe and effective for the management of chronic radiation proctitis. Additional sucralfate treatment did not influence the clinical or endoscopic outcome. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

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M.E. Bigal

2002-10-01

Full Text Available Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05 of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50% and use of rescue medication (dipyrone = 20%, placebo = 47.6% for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia

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Amy S Chappell

2008-12-01

Full Text Available Amy S Chappell1, Laurence A Bradley2, Curtis Wiltse1, Michael J Detke1,3,4, Deborah N D’Souza1, Michael Spaeth51Lilly Research Laboratories, Indianapolis, IN, USA; 2University of Alabama at Birmingham, Birmingham, Alabama, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Harvard Medical School, Boston, MA, USA; 5Practice for Internal Medicine/Rheumatology, Graefelfing, GermanyObjective: Assess the efficacy of duloxetine 60/120 mg (N = 162 once daily compared with placebo (N = 168 in the treatment of patients with fibromyalgia, during six months of treatment.Methods: This was a phase-III, randomized, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of duloxetine.Results: There were no significant differences between treatment groups on the co-primary efficacy outcome measures, change in the Brief Pain Inventory (BPI average pain severity from baseline to endpoint (P = 0.053 and the Patient’s Global Impressions of Improvement (PGI-I at endpoint (P = 0.073. Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Questionnaire pain score, BPI least pain score and average interference score, Clinical Global Impressions of Severity scale, area under the curve of pain relief, Multidimensional Fatigue Inventory mental fatigue dimension, Beck Depression Inventory-II total score, and 36-item Short Form Health Survey mental component summary and mental health score. Nausea was the most common treatment-emergent adverse event in the duloxetine group. Overall discontinuation rates were similar between groups.Conclusions: Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co-primary outcome measures, in this supportive study, duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures.Keywords: fibromyalgia, duloxetine, placebo, double-blind, trial

RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.

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De Soyza, Anthony; Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

2018-01-01

We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more exacerbations in the previous year and pre-defined bacteria in sputum.In this phase III, double-blind, placebo-controlled trial, patients were randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in two treatment regimens consisting of on/off treatment cycles of 14 or 28 days for 48 weeks. The primary end-points were time to first exacerbation and frequency of exacerbations.A total of 416 patients were randomised to the 14-day on/off regimen (ciprofloxacin DPI (n=137) and placebo (n=68)) or the 28-day on/off regimen (ciprofloxacin DPI (n=141) and placebo (n=70)). Ciprofloxacin DPI 14 days on/off significantly prolonged time to first exacerbation versus pooled placebo (median time >336 versus 186 days; hazard ratio 0.53, 97.5% CI 0.36-0.80; p=0.0005) and reduced the frequency of exacerbations compared with matching placebo by 39% (mean number of exacerbations 0.6 versus 1.0; incidence rate ratio 0.61, 97.5% CI 0.40-0.91; p=0.0061). Outcomes for ciprofloxacin DPI 28 days on/off were not statistically significantly different from placebo. The safety profile of ciprofloxacin DPI was favourable.Ciprofloxacin DPI was well tolerated and has the potential to be an effective treatment option in non-cystic fibrosis bronchiectasis. Copyright ©ERS 2018.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

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Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

Placebo Responses to Original vs. Generic ASA Brands During Exposure to Noxious Heat: A Pilot fMRI Study of Neurofunctional Correlates.

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Fehse, Kai; Maikowski, Lea; Simmank, Fabian; Gutyrchik, Evgeny; Meissner, Karin

2015-10-01

We studied the expectation effects associated with brands by labeling placebo interventions (original and generic analgesic) and investigating the potential differences in efficacy between the two placebos in dealing with noxious heat pain, as well as exploring the neurometabolic correlates of the placebo response. We applied a two by two design with two identical placebo interventions that differed only in their labeling. One group was told that they received 500 mg of "Aspirin" (original brand) while the other group was told that they received a popular ASA generic (1A Pharma). After establishing the individual pain level of each subject, we measured pain intensities behaviorally before and after the intervention and looked for corresponding brain areas with increased hemodynamic response using functional magnetic resonance imaging. At the behavioral level, we found decreases in pain intensity from baseline to the intervention condition with the original brand only. At the neuronal level, we specifically observed activations of the anterior insulae under the baseline conditions, complemented by activations of the dorsomedial prefrontal cortex after the interventions. A direct comparison of the two placebo conditions revealed higher values of activation for the bilateral dorsolateral (as well as dorsomedial) prefrontal cortex for the original brand. Our data indicate a behavioral placebo response for the original brand only. Expectations by subjects appear to be triggered not only by the placebo treatment itself but also by the trusted brand, which thus serves as an enhanced placebo. Both processes appear to be based on fronto-cortical neural networks, as these areas showed significantly stronger activations with the original brand. Wiley Periodicals, Inc.

Tribulus terrestris versus placebo in the treatment of erectile dysfunction: A prospective, randomized, double blind study.

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Santos, C A; Reis, L O; Destro-Saade, R; Luiza-Reis, A; Fregonesi, A

2014-05-01

To evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels. Prospective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way. The groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914). At the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total

Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock.

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Kinasewitz, Gary T; Privalle, Christopher T; Imm, Amy; Steingrub, Jay S; Malcynski, John T; Balk, Robert A; DeAngelo, Joseph

2008-07-01

To assess the safety and efficacy of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene (PHP), in patients with distributive shock. Phase II multicenter, randomized (1:1), placebo-controlled study. Fifteen intensive care units in North America. Sixty-two patients with distributive shock, > or = 2 systemic inflammatory response syndrome criteria, and persistent catecholamine dependence despite adequate fluid resuscitation (pulmonary capillary wedge pressure > or = 12). Patients were randomized to PHP at 0.25 mL/kg/hr (20 mg/kg/hr), or an equal volume of placebo, infused for up to 100 hrs, in addition to conventional vasopressor therapy. Because treatment could not be blinded, vasopressors and ventilatory support were weaned by protocol. Sixty-two patients were randomized to PHP (n = 33) or placebo (n = 29). Age, sex, etiology of shock (sepsis in 94%), and Acute Physiology and Chronic Health Evaluation II scores (33.1 +/- 8.3 vs. 30 +/- 7) were similar in PHP and placebo patients, respectively. Baseline plasma nitrite and nitrate levels were markedly elevated in both groups. PHP infusion increased systemic blood pressure within minutes. Overall 28-day mortality was similar (58% PHP vs. 59% placebo), but PHP survivors were weaned off vasopressors faster (13.7 +/- 8.2 vs. 26.3 +/- 21.4 hrs; p = .07) and spent less time on mechanical ventilation (10.4 +/- 10.2 vs. 17.4 +/- 9.9 days; p = .21). The risk ratio (PHP/placebo) for mortality was .79 (95% confidence interval, .39-1.59) when adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II score, and etiology of sepsis. No excess medical interventions were noted with PHP use. PHP survivors left the intensive care unit earlier (13.6 +/- 8.6 vs. 17.9 +/- 8.2 days; p = .21) and more were discharged by day 28 (57.1 vs. 41.7%). PHP is a hemodynamically active nitric oxide scavenger. The role of PHP in distributive shock remains to be determined.

Oral sumatriptan for migraine in children and adolescents: a randomized, multicenter, placebo-controlled, parallel group study.

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Fujita, Mitsue; Sato, Katsuaki; Nishioka, Hiroshi; Sakai, Fumihiko

2014-04-01

The objective of this article is to evaluate the efficacy and tolerability of two doses of oral sumatriptan vs placebo in the acute treatment of migraine in children and adolescents. Currently, there is no approved prescription medication in Japan for the treatment of migraine in children and adolescents. This was a multicenter, outpatient, single-attack, double-blind, randomized, placebo-controlled, parallel-group study. Eligible patients were children and adolescents aged 10 to 17 years diagnosed with migraine with or without aura (ICHD-II criteria 1.1 or 1.2) from 17 centers. They were randomized to receive sumatriptan 25 mg, 50 mg or placebo (1:1:2). The primary efficacy endpoint was headache relief by two grades on a five-grade scale at two hours post-dose. A total of 178 patients from 17 centers in Japan were enrolled and randomized to an investigational product in double-blind fashion. Of these, 144 patients self-treated a single migraine attack, and all provided a post-dose efficacy assessment and completed the study. The percentage of patients in the full analysis set (FAS) population who report pain relief at two hours post-treatment for the primary endpoint was higher in the placebo group than in the pooled sumatriptan group (38.6% vs 31.1%, 95% CI: -23.02 to 8.04, P  = 0.345). The percentage of patients in the FAS population who reported pain relief at four hours post-dose was higher in the pooled sumatriptan group (63.5%) than in the placebo group (51.4%) but failed to achieve statistical significance ( P  = 0.142). At four hours post-dose, percentages of patients who were pain free or had complete relief of photophobia or phonophobia were numerically higher in the sumatriptan pooled group compared to placebo. Both doses of oral sumatriptan were well tolerated. No adverse events (AEs) were serious or led to study withdrawal. The most common AEs were somnolence in 6% (two patients) in the sumatriptan 25 mg treatment group and chest

Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

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Chang Anne B

2012-08-01

Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo.

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Baldwin, David S; Asakura, Satoshi; Koyama, Tsukasa; Hayano, Taiji; Hagino, Atsushi; Reines, Elin; Larsen, Klaus

2016-06-01

Escitalopram is the most selective of the serotonin reuptake inhibitor (SSRI) antidepressants. We conducted a meta-analysis of placebo-controlled studies where escitalopram was used to treat patients with social anxiety disorder (SAD). Data from all randomised, double-blind placebo-controlled studies in SAD with escitalopram from both specialist settings and general practice were used. Patients met the DSM-IV criteria for SAD, were ≥18 years old, and had a Liebowitz Social Anxiety Scale (LSAS) ≥60. The primary outcome measure was the estimated treatment difference in LSAS total score at Week 12. Secondary outcome measures included the estimated treatment difference in the Clinical Global Impression-Severity (CGI-S) score at Week 12. A total of 1598 patients from 3 randomised controlled trials were included in the analyses. Escitalopram (n=1061) was superior to placebo (n=537), with an estimated treatment difference on the LSAS of -9.2 points (95%CI: [-14.4; -4.0], pescitalopram 5mg/day), -4.6 points (95%CI: [-8.1; -1.0], pescitalopram 10mg/day), -10.1 points (95%CI: [-13.7; -6.5], pescitalopram 20mg/day) and -7.3 points (95%CI: [-12.3; -2.2], pescitalopram 10-20mg/day). For the CGI-S, the corresponding values were -0.55 points (95%CI: [-0.79; -0.31], pescitalopram 5mg/day), -0.26 points (95%CI: [-0.42; -0.10], pescitalopram 10mg/day), -0.48 points (95%CI: [-0.64; -0.31], pescitalopram 20mg/day) and -0.29 points (95%CI: [-0.51; -0.07], pescitalopram 10-20mg/day). The withdrawal rate due to adverse events was 7.2% for escitalopram, compared with 4.3% for placebo (pescitalopram showed significant superiority in efficacy versus placebo in the treatment of patients with SAD. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Lactobacillus reuteri strain combination in Helicobacter pylori infection: a randomized, double-blind, placebo-controlled study.

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Francavilla, Ruggiero; Polimeno, Lorenzo; Demichina, Antonella; Maurogiovanni, Giovanni; Principi, Beatrice; Scaccianoce, Giuseppe; Ierardi, Enzo; Russo, Francesco; Riezzo, Giuseppe; Di Leo, Alfredo; Cavallo, Luciano; Francavilla, Antonio; Versalovic, James

2014-01-01

The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection. Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the eradication rate. This is a prospective, double-blind, randomized, placebo-controlled study in a tertiary care setting. A total of 100 H. pylori-positive naive patients received either L. reuteri combination (2×10 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by C-UBT 8 weeks after the completion of therapy. Fifty patients were allocated in each group. During pre-eradication period, C-UBT δ decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo (-13.2±34% vs. 4.3±27%; Preuteri combination (6.8±2.9 vs. 4±3.1; Preuteri combination as compared with placebo-reported side effects (40.9% vs. 62.8%; Preuteri combination (28% vs. 12%; Preuteri combination and 65.9% in placebo (P=NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5). L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in antibiotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori-eradication rate.

Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

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Uri Hertz

Full Text Available Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study

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Stein, Dan J; Andersen, Elisabeth Anne Wreford; Tonnoir, Brigitte

2007-01-01

OBJECTIVE: A randomized, placebo controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive-compulsive disorder (OCD), using paroxetine as the active reference. RESEARCH DESIGN AND METHODS: A total of 466 adults with OCD from specialized...... clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10 mg/day (n = 116), escitalopram 20 mg/day (n = 116), paroxetine 40 mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy...... of adverse events, and on changes in vital signs (blood pressure and pulse). Main outcome measures; RESULTS: Escitalopram 20 mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10 mg/day and paroxetine 40 mg/day were also effective...

[Extracorporeal shockwave therapy (ESWT) as therapeutic option in supraspinatus tendon syndrome? One year results of a placebo controlled study].

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Schmitt, J; Tosch, A; Hünerkopf, M; Haake, M

2002-07-01

Extracorporeal shock wave therapy (ESWT) is seen as a therapeutic option in the treatment of chronic supraspinatus tendinitis by some authors. To test whether ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33 mJ/mm2 is clinically superior to a sham ESWT treatment, a prospective, randomized, single-blinded, placebo-controlled study with an independent observer was performed. Forty patients were treated either by verum ESWT or sham ESWT under local anesthesia. Target criteria were the age-corrected Constant score, pain at rest and during activity on a visual analogue scale, and subjective improvement. Patients who reported no subjective improvement after 12 weeks were deblinded and received verum ESWT if they had belonged to the placebo group (partial crossover). The results of the verum group lie within the range of results for ESWT published by other authors. Patients in the placebo group with local anesthetic showed equally good results. At 12 weeks, and 1 year after intervention, no difference could be found between the verum and placebo groups regarding Constant score, pain, shoulder function, or subjective improvement. The nonresponders to the placebo ESWT continued to show no improvement after receiving verum ESWT. This contradicts a specific ESWT effect. Based on the results of this placebo-controlled study, ESWT appears to have no clinically relevant effect on supraspinatus tendinitis. The study underlines the importance of a control group in evaluating new treatment methods for diseases with unknown natural history.

A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.

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Marcus, Ronald N; Owen, Randall; Kamen, Lisa; Manos, George; McQuade, Robert D; Carson, William H; Aman, Michael G

2009-11-01

To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions-Improvement score. Safety and tolerability were also assessed. At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, -12.4; 10 mg/day, -13.2; 15 mg/day, -14.4; versus placebo, -8.4; all p autistic disorder.

A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision

DEFF Research Database (Denmark)

Agren, Magnus S; Ostenfeld, Ulla; Kallehave, Finn

2006-01-01

The purpose of this randomized, double-blind, placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years, were centrally randomized to either treatment with 3% zinc oxide...... range 42-71 days) for the zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc oxide increased (p zinc levels to 1,540 (1,035-2,265) microM and decreased (p zinc oxide (n = 3) than placebo......-treated patients (n = 12) were prescribed postoperative antibiotics (p = 0.005). Serum-zinc levels increased (p Zinc oxide was not associated with increased pain by the visual analog scale, cellular...

Double-blind placebo-controlled pilot study of paroxetine for specific phobia.

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Benjamin, J; Ben-Zion, I Z; Karbofsky, E; Dannon, P

2000-04-01

Drugs are not recognized as a standard treatment for specific phobia, despite its apparent similarities to other kinds of phobia. Reluctance on the part of patients and clinicians to see the disorder as more than normal anxiety may explain the apparent resistance to pharmacotherapy. Eleven patients fulfilling DSM-IV criteria for specific phobia were randomized to 4 weeks of double-blind treatment with placebo or paroxetine up to 20 mg/day. They were assessed weekly with the Fear Questionnaire and the Hamilton Rating Scale for Anxiety. Paroxetine showed significant superiority in reducing all measures (ANCOVA for reductions in phobia scores F=7.9, P=0.02). One out of six patients responded to placebo, compared to three out of five patients on paroxetine. This new therapeutic option (i.e. drug treatment) for specific phobia deserves further examination in a larger trial.

The Cure Rate after Placebo or No Therapy in American Cutaneous Leishmaniasis: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Gláucia Fernandes Cota

Full Text Available There are few drugs with proven efficacy in cutaneous leishmaniasis (CL, and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities. Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator. To support the use of placebo as a comparator, two main points need to be addressed: 1--the cure rate without any therapeutic intervention and 2--the damage caused by CL and its impact on patients.The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials.The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the PubMed and LILACS databases. Studies were included if they reported cure rates using placebo or no treatment in American CL.Thirteen studies of a total of 352 patients were ultimately included in this review. The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three ("initial cure" and nine ("definitive cure" months after "no treatment" or placebo use were 26% (CI95%: 16 to 40% and 26% (CI95%:16 to 38%, respectively. Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20% than for L. mexicana infection (44%, CI95%:19 to 72%, p = 0.002. Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%.These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis. Therefore, from this point, the crucial question to consider

Misoprostol for cervical priming prior to hysteroscopy in postmenopausal and premenopausal nulliparous women; a multicentre randomised placebo controlled trial

NARCIS (Netherlands)

Tasma, M L; Louwerse, M D; Hehenkamp, W J; Geomini, P M; Bongers, M Y; Veersema, S; van Kesteren, P J; Tromp, E; Huirne, J A; Graziosi, G C

OBJECTIVE: To evaluate the reduction of pain by misoprostol compared with placebo prior to hysteroscopy in postmenopausal and premenopausal nulliparous women. DESIGN: Randomised multicentre double-blind placebo controlled trial. SETTING: Two Dutch teaching hospitals and one Dutch university medical

Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Rezaei, Farzin; Ghaderi, Ebrahim; Mardani, Roya; Hamidi, Seiran; Hassanzadeh, Kambiz

2016-06-01

To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P methamphetamine dependence. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode

NARCIS (Netherlands)

Storosum, Jitschak G.; Wohlfarth, Tamar; Gispen-de Wied, Christine C.; Linszen, Don H.; Gersons, Berthold P. R.; van Zwieten, Barbara J.; van den Brink, Wim

2005-01-01

Objective: The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic/depressive episode. If so, this would be a strong ethical argument

A randomized double-blind placebo-controlled crossover-style trial of buspirone in functional dysphagia and ineffective esophageal motility.

Science.gov (United States)

Aggarwal, Nitin; Thota, Prashanthi Nagavenkata; Lopez, Rocio; Gabbard, Scott

2018-02-01

Studies suggest that Ineffective Esophageal Motility (IEM) is the manometric correlate of Functional Dysphagia (FD). Currently, there is no accepted therapy for either condition. Buspirone is a serotonin modulating medication and has been shown to augment esophageal peristaltic amplitude in healthy volunteers. We aimed to determine if buspirone improves manometric parameters and symptoms in patients with overlapping IEM/FD. We performed a prospective, double-blind, placebo-controlled, crossover-style trial of 10 patients with IEM/FD. The study consisted of two 2-week treatment arms with a 2-week washout period. Outcomes measured at baseline, end of week 2, and week 6 include high resolution esophageal manometry (HREM), the Mayo Dysphagia Questionnaire-14 (MDQ-14), and the GERD-HRQL. The mean age of our 10 patients was 53 ± 9 years and 70% were female. After treatment with buspirone, 30% of patients had normalization of IEM on manometry; however, there was 30% normalization in the placebo group as well. Comparing buspirone to placebo, there was no statistically significant difference in the HREM parameters measured. There was also no statistically significant difference in symptom outcomes for buspirone compared to placebo. Of note, patients had a statistically significant decrease in the total GERD-HRQL total score when treated with placebo compared to baseline levels. Despite previous data demonstrating improved esophageal motility in healthy volunteers, our study shows no difference in terms of HREM parameters or symptom scores in IEM/FD patients treated with buspirone compared to placebo. Further research is necessary to identify novel agents for this condition. © 2017 John Wiley & Sons Ltd.

A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage.

Science.gov (United States)

Misra, U K; Kalita, J; Pandey, S; Mandal, S K; Srivastava, M

2005-12-15

Due of paucity of studies on stress ulcer prophylaxis in intracerebral hemorrhage (ICH), we have evaluated the usefulness of ranitidine and sucralfate in preventing gastric hemorrhage (GH) in patients with ICH. In a hospital-based randomized placebo-controlled study, patients with CT-proven ICH within 7 days of ictus were randomized into ranitidine 50 mg i.v. eight hourly, sucralfate 1 g six hourly and placebo groups. Patients were conservatively managed. Primary endpoint was occurrence of GH within 15 days of ictus and secondary endpoint 1-month mortality. The mean age of the patients was 57.2 (range 25-90) years and 40 were females. There were 45 patients in ranitidine, 49 in sucralfate and 47 in placebo group. Demographic, clinical and radiological features were not significantly different in 3 groups. GH occurred in 11 (23.4%) patients in placebo, 5 (11.1%) in ranitidine and 7 (14.3%) in sucralfate group, which was not significant. Only one female had GH. There were 13 (27.7%) deaths in placebo, 5 (11.1%) in ranitidine and 12 (24.5%) in sucralfate group. Pneumonia occurred in placebo group in 5 (10.6%), ranitidine in 2 (4.4%) and sucralfate in 5 (10.2%) patients, which was not significantly different. Ranitidine and sucralfate do not seem to significantly prevent GH or reduce 1-month mortality.

Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone

International Nuclear Information System (INIS)

Lussier, A.; LeBel, E.

1987-01-01

Gastrointestinal blood loss is one of the most serious clinical events induced by drugs. To date, almost no nonsteroidal anti-inflammatory drug has been shown to be devoid of that side effect in a strictly controlled study. The objective of this study was to assess quantitatively, by use of radioactive chromium (chromium-51)-labeled red blood cells, gastrointestinal blood loss associated with nabumetone (1000 mg daily), aspirin (3.6 g daily), and placebo. A total of 37 normal subjects, divided among the three treatment groups and a fourth group that received no treatment, were assessed clinically and quantitatively for gastrointestinal blood loss over a period of 28 days of active treatment. The results with chromium-51, analyzed on a logarithmic scale, revealed no statistically significant differences between the nabumetone, placebo, and control groups. Gastrointestinal blood loss in the aspirin group, however, was elevated when compared with all other groups at a high level of statistical significance (p less than 0.001). It is concluded that, under conditions in which aspirin causes substantial gastrointestinal microbleeding, nabumetone is not significantly different from placebo

Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study

OpenAIRE

Krymchantowski,Abouch V.; Barbosa,Jackeline S.; Cheim,Celia; Alves,Luiz A.

2001-01-01

Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, wer...

NMDA receptor antagonists interventions in schizophrenia: Meta-analysis of randomized, placebo-controlled trials.

Science.gov (United States)

Kishi, Taro; Iwata, Nakao

2013-09-01

We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD = -0.25, CI = -0.72, 0.23, p = 0.31, N = 6, n = 347), positive symptoms (SMD = -0.20, CI = -0.70, 0.31, p = 0.44, N = 4, n = 205), and negative symptoms (SMD = -0.69, CI = -1.65, 0.27, p = 0.16, N = 4, n = 205), and Clinical Global Impression Severity scale (SMD = -0.27, CI = -1.20, 0.65, p = 0.56, N = 3, n = 177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR = 1.23, CI = 0.89-1.70, p = 0.20, N = 8, n = 396, side effects: RR = 1.86, CI = 0.84-4.13, p = 0.13, N = 6, n = 359, inefficacy/worsening psychosis: RR = 0.70, CI = 0.20-2.38, p = 0.56, N = 7, n = 380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD = -0.77, CI = -1.27, -0.28, p = 0.002, N = 3, n = 71). While NMDAR-ANTs caused weight loss compared with placebo (SMD = -0.42, CI = -0.73, -0.11, p = 0.008, N = 3, n = 165), amantadine caused more frequent insomnia than placebo (RR = 3.83, CI = 1.41-10.38, p = 0.008, NNH = 9, p = 0.002, N = 2, n = 147). Our results indicate that NMDAR-ANTs as adjunctive therapy may improve

Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial.

Directory of Open Access Journals (Sweden)

Elise Mok

Full Text Available Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD. We evaluated the functional benefit of 4 months oral glutamine in DMD.30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine, markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine, serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage, safety and oral nutrient intake. There was no improvement in the primary end point (walking speed or in secondary measures of muscle function (2-minute walk test, work, power in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.(ClinicalTrials.gov NCT00296621.

Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: A randomized, double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Andresen, Sven R; Bing, Jette; Hansen, Rikke Bod Middelhede

2016-01-01

, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment...... with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation...... included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (-0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity...

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

Science.gov (United States)

Nakato, Rui; Manabe, Noriaki; Shimizu, Sayako; Hanayama, Kozo; Shiotani, Akiko; Hata, Jiro; Haruma, Ken

2017-01-01

The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD. © 2017 S. Karger AG, Basel.

Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

Science.gov (United States)

Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

2009-05-01

Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C

2016-02-01

Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. Published by Elsevier Ireland Ltd.

Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain.

Science.gov (United States)

Klinger, Regine; Kothe, Ralph; Schmitz, Julia; Kamping, Sandra; Flor, Herta

2017-10-01

This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. The patients were either told that the "solution reduces pain and improves physical capacity" or the "solution is neutral, a placebo." Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were as follows: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10) and self-rated functional capacity (0%-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham "opioid" solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F(3.12,144.21) = 25.05, P pain ratings (F(1.99,87.40) = 18.12, P pain expectations, and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Necek Magdalena

2008-05-01

Full Text Available Abstract Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713

Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group

DEFF Research Database (Denmark)

Andersen, J T; Ekman, P; Wolf, H

1995-01-01

rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically. RESULTS......OBJECTIVES. To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months. METHODS. This was a multicenter, double-blind, placebo....... The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P

Neuromodulation of conditioned placebo/nocebo in heat pain: anodal vs cathodal transcranial direct current stimulation to the right dorsolateral prefrontal cortex.

Science.gov (United States)

Egorova, Natalia; Yu, Rongjun; Kaur, Navneet; Vangel, Mark; Gollub, Randy L; Dougherty, Darin D; Kong, Jian; Camprodon, Joan A

2015-07-01

Placebo and nocebo play an important role in clinical practice and medical research. Modulating placebo/nocebo responses using noninvasive brain stimulation methods, such as transcranial direct current stimulation (tDCS), has the potential to harness these effects to therapeutic benefit in a clinical setting. In this study, we assessed the effect of anodal and cathodal tDCS over the right dorsolateral prefrontal cortex (rDLPFC) on conditioned placebo/nocebo cue response to heat pain. Two matched groups of healthy volunteers were subjected to an identical session of conditioning, during which low and high cues (abstract images) were associated with low and high pain levels, respectively. Twenty-minute 2-mA tDCS (either anodal or cathodal) over the rDLPFC was applied. The influence of tDCS current polarity (anodal vs cathodal) on placebo and nocebo was assessed, using subjects' pain ratings in response to identical pain preceded by the conditioned high or low cues. The duration of cue presentation varied to allow either fully conscious or subliminal processing. Significant placebo and nocebo effects in the anodal but not the cathodal group were elicited with the conditioning paradigm. This study provides evidence of a possibility to modulate the conditioned placebo and nocebo effect by changing the excitability of the rDLPFC using tDCS.

Efficacy of polyglucosamine for weight loss?confirmed in a randomized double-blind, placebo-controlled clinical investigation

OpenAIRE

Pokhis, Karina; Bitterlich, Norman; Cornelli, Umberto; Cassano, Giuseppina

2015-01-01

Background The purpose of this clinical study was to ascertain whether low molecular weight chitosan polyglucosamine is able to produce significantly better weight loss than placebo. Method 115 participants were included in the study. We used a two-center randomized, double blind, placebo-controlled design. The participants followed a standard treatment (ST), which included the combination of a low-calorie diet achieved through creating a daily calorie deficit (500 cal) and an increased daily...

Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Phillips, Katharine A; Keshaviah, Aparna; Dougherty, Darin D; Stout, Robert L; Menard, William; Wilhelm, Sabine

2016-09-01

Body dysmorphic disorder is common, distressing, and often severely impairing. Serotonin reuptake inhibitors appear efficacious, but the few existing pharmacotherapy studies were short term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted to the authors' knowledge. The authors report results from the first relapse prevention study in body dysmorphic disorder. Adults (N=100) with DSM-IV body dysmorphic disorder received open-label escitalopram for 14 weeks (phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for 6 months (phase 2). Reliable and valid outcome measures were utilized. In phase 1, 67.0% of treated subjects and 81.1% of subjects who completed phase 1 responded to escitalopram. Body dysmorphic disorder severity (in both the intent-to-treat and the completer groups) and insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of phase 1. In phase 2, time to relapse was significantly longer with escitalopram than with placebo treatment (hazard ratio=2.72, 95% CI=1.01-8.57). Phase 2 relapse proportions were 18% for escitalopram and 40% for placebo. Among escitalopram-treated subjects, body dysmorphic disorder severity significantly decreased over time during the continuation phase, with 35.7% of subjects showing further improvement. There were no significant group differences in body dysmorphic disorder severity or insight, depressive symptoms, psychosocial functioning, or quality of life. Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed than did placebo-treated subjects. Body dysmorphic disorder severity significantly improved during 6 additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects experienced further improvement.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

Science.gov (United States)

Kennedy, Stephen B; Bolay, Fatorma; Kieh, Mark; Grandits, Greg; Badio, Moses; Ballou, Ripley; Eckes, Risa; Feinberg, Mark; Follmann, Dean; Grund, Birgit; Gupta, Swati; Hensley, Lisa; Higgs, Elizabeth; Janosko, Krisztina; Johnson, Melvin; Kateh, Francis; Logue, James; Marchand, Jonathan; Monath, Thomas; Nason, Martha; Nyenswah, Tolbert; Roman, François; Stavale, Eric; Wolfson, Julian; Neaton, James D; Lane, H Clifford

2017-10-12

The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (PLiberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS).

Science.gov (United States)

Rossi, Simone; Ferro, Marisa; Cincotta, Massimo; Ulivelli, Monica; Bartalini, Sabina; Miniussi, Carlo; Giovannelli, Fabio; Passero, Stefano

2007-03-01

There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation (rTMS) as a neuromodulatory treatment. However, there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects, which may be particularly strong in psychiatric patients. This is due to the fact that existing sham rTMS procedures are less than optimal. A new placebo tool is introduced here, called real electro-magnetic placebo (REMP) device, which can simulate the scalp sensation induced by the real TMS, while leaving both the visual impact and acoustic sensation of real TMS unaltered. Physical, neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1Hz and 20Hz rTMS procedures (at different intensities) were tested in subjects who were expert or naïve of TMS. Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures, namely the commercially available Magstim sham coil and tilting the real coil by 90 degrees . The REMP device, besides producing scalp sensations similar to the real TMS, attenuated the TMS-induced electric field (as measured by a dipole probe) to a biologically inactive level. Behaviourally, neither expert nor naïve TMS subjects identified the "coil at 90 degrees " or the "Magstim sham coil" as a real TMS intervention, whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real. The "goodness of sham" of the REMP device is demonstrated by physical, neurophysiological, and behavioural results. Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS, as in case of patients undergoing a clinical rTMS trial.

Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects

International Nuclear Information System (INIS)

Coleman, C. Norman; Kelly, Laura; Riese Daly, Nancy; Beard, Clair; Kaplan, Irving; Lamb, Carolyn; Propert, Kathleen; Manola, Judith

2002-01-01

Purpose: On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score. Methods and Materials: Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week. Results: Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation. Conclusion: The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non

Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.

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Chollet, François; Tardy, Jean; Albucher, Jean-François; Thalamas, Claire; Berard, Emilie; Lamy, Catherine; Bejot, Yannick; Deltour, Sandrine; Jaillard, Assia; Niclot, Philippe; Guillon, Benoit; Moulin, Thierry; Marque, Philippe; Pariente, Jérémie; Arnaud, Catherine; Loubinoux, Isabelle

2011-02-01

Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial

Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical Trial.

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Smith, Stephen R; Murray, David; Pockney, Peter G; Bendinelli, Cino; Draganic, Brian D; Carroll, Rosemary

2018-01-01

Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking. The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage. This was a prospective, double-blind, placebo-controlled, randomized clinical trial. The study was conducted at a tertiary referral university hospital in Australia. Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265). A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo. The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates. There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use. A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes. Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

EFFICACY OF HYOSCINE BUTYLBROMIDE IN TREATMENT OF IRRITABLE BOWEL SYNDROME IN CHILDREN: PLACEBO-CONTROLLED TRIAL

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K.V. Arifullina

2008-01-01

Full Text Available The activity of hyoscine butylbromide (buscopan was evaluated in a placebobcontrolled trial, on pediatric patients with algid type of irritable bowel syndrome. Hyoscine butylbromide favored to the increase of quality of life in pediatric patients, alleviation of clinical symptoms of disease, reliable decrease of malonic dialdehyde and increase of antioxidant activity of blood plasma significantly superior to placebo. Clinical efficacy of hyoscine butylbromide accompanies to its good tolerance and safety.Key words: children, irritable bowel syndrome, hyoscine butylbromide, placebo controlled trial.

Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

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Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

2009-01-01

To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

An Extract of Glycyrrhiza glabra (GutGard Alleviates Symptoms of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study

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Kadur Ramamurthy Raveendra

2012-01-01

Full Text Available A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of GutGard, an extract of Glycyrrhiza glabra, in patients with functional dyspepsia. The primary outcome variables of the study were the change in the severity symptoms and the global assessment of efficacy. The quality of life was evaluated as a secondary outcome measure. The patients received either placebo or GutGard (75 mg twice daily for 30 days. Efficacy was evaluated in terms of change in the severity of symptoms (as measured by 7-point Likert scale, the global assessment of efficacy, and the assessment of quality of life using the short-form Nepean Dyspepsia Index. In comparison with placebo, GutGard showed a significant decrease (P≤.05 in total symptom scores on day 15 and day 30, respectively. Similarly, GutGard showed marked improvement in the global assessment of efficacy in comparison to the placebo. The GutGard group also showed a significant decrease (P≤.05 in the Nepean dyspepsia index on day 15 and 30, respectively, when compared to placebo. GutGard was generally found to be safe and well-tolerated by all patients. GutGard has shown significant efficacy in the management of functional dyspepsia.

A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico.

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Rossignol, J F; Hidalgo, H; Feregrino, M; Higuera, F; Gomez, W H; Romero, J L; Padierna, J; Geyne, A; Ayers, M S

1998-01-01

Sixty-six patients with human immunodeficiency virus infection and diarrhoea caused by Cryptosporidium parvum were enrolled in a double-'blind' placebo-controlled study to evaluate the safety and efficacy of nitazoxanide in the treatment of cryptosporidiosis related to the acquired immune deficiency syndrome. Patients were randomly assigned to one of 3 treatment groups and received either 500 mg twice daily of nitazoxanide, 1000 mg twice daily of nitazoxanide, or placebo orally for 14 d; the patients on nitazoxanide then crossed over to placebo while the placebo patients crossed over to nitazoxanide therapy at either the high or low dose depending on their randomization. Three post-treatment faecal examinations were conducted on days 15, 22 and 29 following initiation of treatment: patients were considered 'cured' if none revealed any C. parvum oocysts. Both doses of nitazoxanide produced parasitological cure rates superior to the placebo responses (12/19 [63%, P = 0.016] for patients receiving 1 g/d and 10/15 [67%, P = 0.013] for those receiving 2 g/d). Parasitological cure was correlated with the complete resolution of the diarrhoeal syndrome in 19 of the 22 treated patients who were considered parasitologically cured (86%). Both doses of nitazoxanide were well tolerated by the patients.

Effects of Kivia powder on gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study.

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Udani, Jay K; Bloom, David W

2013-06-08

To evaluate the efficacy of Kivia powder on supporting overall gut health through the relief of the discomfort of occasional constipation. Randomized, double-blind, placebo-controlled, parallel-group trial. The investigational product for this study was Kivia powder (Vital Food Processors Ltd., Auckland, New Zealand), containing the active ingredient Zyactinase™, 5.5 g taken daily for four weeks. One hundred thirty-eight subjects reporting occasional constipation were screened and 87 were randomized to placebo (n = 44) and product (n = 43). Bowel movement frequency, as measured by both average daily spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM), were the same in both groups at baseline. There were significant increases in spontaneous bowel movements at week 1 (p = 0.001), week 2 (p = 0.001), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. SBM demonstrated significant differences between the treatment group and the placebo group at week 3 (p = 0.000), and week 4 (p = 0.020). The treatment group demonstrated a significantly higher rate of SBM at week 3 (p = 000) and from baseline to week 4 (p = 0.019). Significant increases in complete spontaneous bowel movements were observed at week 1 (p = 0.000), week 2 (p = 0.000), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. Moreover, CSBM was significantly higher for the treatment group compared to placebo at week 2 (p = 0.001). The change in average daily CSBM from baseline to week 2 was significantly higher in the treatment group than in the placebo group (p = 0.004).Abdominal discomfort or pain demonstrated significant differences between groups at week 1 (p = 0.044) and week 3 (p = 0.026). Flatulence was significantly lower for active group compared to placebo at week 2 (p = 0.047) and week 3 (p = 0.023). The number of bowel movements associated with urgency was significantly lower in the treatment group compared to the placebo group at week 3 (p = 0

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

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Burbank F

2014-02-01

Full Text Available Fred Burbank Salt Creek International Women's Health Foundation, San Clemente, CA, USA Purpose: To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials. Patients and methods: Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes. Results: For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Qbetween subgroups =0.25, PQ≥0.62. Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Qbetween subgroups =4.59, PQ≤0.03 and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Qbetween subgroups =5.50, PQ≤0.02. Conclusion: For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials. Keywords: sham effect, placebo effect, trial design, crossover study, parallel study, counterstimulation

Effect of an herbal/botanical supplement on recovery from delayed onset muscle soreness: a randomized placebo-controlled trial.

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Rynders, Corey A; Weltman, Judy Y; Rynders, Sara D; Patrie, James; McKnight, John; Katch, Frank I; Hertel, Jay; Weltman, Arthur

2014-01-01

We examined the effects of a proprietary herbal/botanical supplement (StemSport, Stemtech, San Clemente, CA.) suggested to increase circulating stem cells, decrease inflammation, and attenuate exercise induced muscle damage on recovery from delayed onset muscle soreness (DOMS). Sixteen subjects (male = 7, female = 9; age 23.8 ± 10 years; height 171.9 ± 10 cm, mass 72.2 ± 15 kg) were randomized in a crossover, double-blind, placebo controlled trial to receive a placebo or StemSport supplement (6150 mg/day) for 14 days. DOMS was induced on day 7 for both placebo and active conditions in the non-dominant elbow flexor group with repeated eccentric repetitions. Muscle swelling (biceps girth), elbow flexor isometric strength (hand held dynamometer), muscle pain/tenderness (visual analog scale), range of motion (active elbow flexion and extension), and inflammation (hsCRP, IL6, and TNF-α) were measured at baseline and at 24 h, 48 h, 72 h, and 168 h (1 week) post eccentric exercise. The crossover washout period was ≥14 days. No significant condition-by-time interactions between placebo and StemSport supplementation were observed with regard to measures of pain (p = 0.59), tenderness (p = 0.71), isometric strength (p = 0.32), elbow flexion (p = 0.45), muscle swelling (p = 0.90), or inflammation (p > 0.90). Decrements in elbow extension range of motion 48 h post-exercise were less after StemSport supplementation (Δ elbow extension 48 h post; StemSport, -2.0 deg; placebo, -10 deg; p = 0.003). These data suggest that compared to placebo, StemSport supplementation does not improve outcome measures related to muscle recovery after acute upper-arm induced DOMS.

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial

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Ahmad Ghanizadeh

2017-04-01

Full Text Available Objective: Glutamate is considered a target for treating obsessive-compulsive disorder (OCD. The efficacy and safety of the nutritional supplement of N-Acetylcysteine (NAC as an adjuvant to serotonin reuptake inhibitor (SSRI for treating children and adolescents with OCD has never been examined.Methods: This was a 10-week randomized double-blind placebo-controlled clinical trial with 34 OCD outpatients. The patients received citalopram plus NAC or placebo. Yale-Brown Obsessive-Compulsive Scale (YBOCS and Pediatric Quality of Life Inventory (PedsQL™ were used. Adverse effects were monitored.Results: YBOCS score was not different between the two groups at baseline, but the score was different between the two groups at the end of this trial (P<0.02. The YBOCS score of NAC group significantly decreased from 21.0(8.2 to 11.3(5.7 during this study. However, no statistically significant decrease of YBOCS was found in the placebo group. The Cohen’s d effect size was 0.83.The mean change of score of resistance/control to obsessions in the NAC and placebo groups was 1.8(2.3 and 0.8(2.1, respectively (P = 0.2. However, the mean score of change for resistance/control to compulsion in the NAC and placebo groups was 2.3(1.8 and 0.9(2.3, respectively. Cohen’s d effect size was 0.42.The score of three domains of quality of life significantly decreased in N-Acetylcysteine group during this trial. However, no statistically significant decrease was detected in the placebo group. No serious adverse effect was found in the two groups.Conclusion: This trial suggests that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents. In addition, it is well tolerated.

Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

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Tarumi, Yoko; Wilson, Mitchell P; Szafran, Olga; Spooner, G Richard

2013-01-01

The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. To assess the efficacy of docusate in hospice patients. This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis.

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Strand, Vibeke; van Vollenhoven, Ronald F; Lee, Eun Bong; Fleischmann, Roy; Zwillich, Samuel H; Gruben, David; Koncz, Tamas; Wilkinson, Bethanie; Wallenstein, Gene

2016-06-01

To evaluate effects of tofacitinib or adalimumab on patient-reported outcomes (PROs) in patients with moderate to severe RA and inadequate responses to MTX. In this 12-month, phase 3, randomized controlled trial (ORAL Standard), patients (n = 717) receiving background MTX were randomized to tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks or placebo. PROs included HAQ-Disability Index, Patient Global Assessment of Arthritis, Patient Assessment of Arthritis Pain, health-related quality of life (Short Form-36 [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) and sleep (Medical Outcomes Study-Sleep). At month 3, tofacitinib 10 mg BID treatment resulted in significant changes from baseline vs placebo across all PROs, sustained to month 12, with the highest number of patients reporting improvements ⩾minimum clinically important differences vs placebo (P tofacitinib 5 mg BID and adalimumab were similar and statistically significant vs placebo across most PROs, excluding SF-36 Mental Component Score and Social Functioning, Role Emotional, and Mental Health domains, with significantly more patients reporting improvements ⩾minimum clinically important differences. Numbers Needed to Treat were lowest for tofacitinib 10 mg BID and similar between tofacitinib 5 mg BID and adalimumab. Patients with moderate to severe RA and inadequate responses to MTX reported improvements across a broad range of PROs with tofacitinib 5 and 10 mg BID and adalimumab that were significantly superior to placebo. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

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Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomised Double Blind Placebo Controlled Trial

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Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, GVJA; Prasad, Sai; Rao, TS; Boslego, John; Bhan, Maharaj Kishan

2015-01-01

Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; Protavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients

Safety and Efficacy of MLC601 in Iranian Patients after Stroke: A Double-Blind, Placebo-Controlled Clinical Trial

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A. A. Harandi

2011-01-01

Full Text Available Objective. To investigate the safety and efficacy of MLC601 (NeuroAid as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 1 month ischemic stroke. All patients were given either MLC601 (100 patients or placebo (50 patients, 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P>.05. Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P<.001. Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases.

Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

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Kupchak Brian R

2009-07-01

Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

The effect of magnesium on maternal blood pressure in pregnancy-induced hypertension. A randomized double-blind placebo-controlled trial

DEFF Research Database (Denmark)

Rudnicki, M; Frölich, A; Rasmussen, W F

1991-01-01

The effects of magnesium were compared with those of placebo in a randomized double-blind controlled study of 58 patients with pregnancy-induced hypertension, of whom 27 received magnesium and 31 placebo. Twenty patients in each group were nulliparas. The treatment comprised 48 h of either intrav...

Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial.

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Husain, Muhammad I; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza R; Hamirani, Munir M; Hodsoll, John; Qurashi, Inti; Deakin, John Fw; Young, Allan H

2017-09-01

Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms. Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks. A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample. ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

Imiquimod 3.75% Cream Applied Daily to Treat Anogenital Warts: Combined Results from Women in Two Randomized, Placebo-Controlled Studies

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David A. Baker

2011-01-01

Full Text Available Objective. To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts. Methods. In two studies 534 women ≥12 years of age (mean 33.4 with 2–30 warts (mean 7.9 and total wart area ≥10 mm2 (mean 166.3 were randomized (1 : 2 : 2 to placebo (106, imiquimod 2.5% (212 or 3.75% (216 creams applied once daily until complete clearance or a maximum of 8 weeks. Results. For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P=0.008 imiquimod 2.5%, and P<0.001 3.75% versus placebo. Mean changes in wart counts were −10.7%, −50.9%, and −63.5% (per-protocol, P<0.001 each active versus placebo and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%. Conclusions. Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts.

The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials

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Papadopoulos George

2007-10-01

Full Text Available Abstract Background Topiramate is approved for the prophylaxis (prevention of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ scores versus placebo (p Methods Mean MSQ and Medical Outcome Study Short Form 36 (SF-36 change scores (baseline to each double-blind assessment point were calculated for pooled intent-to-treat (ITT patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: Results Of 756 patients (mean age 39.8 years, 86% female, 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p Conclusion Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a ≥ 50% migraine frequency reduction.

Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS.

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Glintborg, Dorte; Altinok, Magda Lambaa; Ravn, Pernille; Stage, Kurt Bjerregaard; Højlund, Kurt; Andersen, Marianne

2018-03-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n  = 21) or placebo ( n  = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m 2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P  = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P   PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged. © 2018 The authors.

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

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Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Data from ‘Placebo Enhances Reward Learning in Healthy Individuals’

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Zsolt Turi

2018-04-01

Full Text Available This dataset contains three repeated measures of a standard reward-based reinforcement-learning task from 29 healthy male individuals who participated in three experimental sessions exploring cognitive placebo effects on reward learning. The dataset includes behavioural data (accuracy, reaction times during learning and transfer, estimates of model-free computational analysis, self-reported arousal values, and expectations about the interventions’ efficacy. The data were collected in 2014 at the Department of Clinical Neurophysiology, University Medical Center Goettingen, Germany. The data collection and formal analysis used a triple-blind study design as participants, operator and analyst were unaware of conditions. A github repository contains data and analyses for the paper “Placebo Intervention Enhances Reward Learning in Healthy Individuals”. The dataset can be used for further analysis, reference, validation studies, teaching purposes, and collaborative research. Funding statement: This study was supported by the DFG (PA 419/15-1 awarded to WP. The preparation of this manuscript was supported by the “Research program, University Medical Center, University of Goettingen” awarded to Z.T.

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

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Clive Ballard

2008-04-01

Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

Effects of sertindole on cognition in clozapine-treated schizophrenia patients - a double-blinded, randomized, placebo-controlled trial

DEFF Research Database (Denmark)

Nielsen, R E; Levander, S; Nielsen, Jimmi

Nielsen RE, Levander S, Thode D, Nielsen J. Effects of sertindole on cognition in clozapine-treated schizophrenia patients. Objective:  To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial....... Method:  A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. Results:  Participants displayed substantial cognitive deficits......, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative...

A double-blind comparison of clebopride and placebo in dyspepsia secondary to delayed gastric emptying.

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Bavestrello, L; Caimi, L; Barbera, A

1985-01-01

Seventy-six patients suffering from dyspeptic symptoms secondary to roentgenologically demonstrated delayed gastric emptying were treated with clebopride (0.5 mg TID) or with placebo during a three-month double-blind trial. Clebopride was more effective (P less than or equal to 0.001) than placebo in reducing or relieving symptoms and roentgenological findings associated with delayed gastric emptying. No interactions of clebopride with concomitant drugs or coexisting disorders were observed, and the incidence of side effects was low. We conclude that clebopride will be beneficial in the management of patients with delayed gastric emptying.

Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension.

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Schwarzer, R; Kivaranovic, D; Mandorfer, M; Paternostro, R; Wolrab, D; Heinisch, B; Reiberger, T; Ferlitsch, M; Gerner, C; Trauner, M; Peck-Radosavljevic, M; Ferlitsch, A

2018-01-01

The amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis. To assess the haemodynamic effects of taurine supplementation in patients with cirrhosis and varices. Patients with hepatic venous pressure gradient (HVPG) ≥12 mm Hg were included in this prospective proof of concept study. Concomitant nonselective beta-blockers therapy was not allowed. Patients received either 4 weeks of oral taurine (6 g/day), or placebo, prior to evaluation of HVPG response. Thirty patients were screened and 22 included in the efficacy analysis (12 taurine/10 placebo; 64% male, mean age: 52 ± 11 years, Child A: 9%, B:64%, C:27%, ascites:68%). In the taurine group, mean HVPG dropped from 20 mm Hg (±4) at baseline to 18 mm Hg (±4) on day 28 (mean relative change: -12%, P = .0093). In the placebo group, mean HVPG increased from 20 mm Hg (±5) at baseline to 21 mm Hg (±5) on day 28 (mean relative change:+2%, P = .4945). Taurine had no significant effects on systemic haemodynamics. Seven of 12 patients (58%) on taurine achieved a HVPG response >10%, compared to none in the placebo group (P = .0053). In a multivariate linear model, HVPG reduction was significantly larger in the taurine group compared to placebo group (P = .0091 and P = .0109 for absolute and relative change respectively). Treatment-related adverse events included gastrointestinal discomfort and fatigue, and were usually mild and comparable between treatment groups. Taurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted. © 2017 John Wiley & Sons Ltd.

Maintenance nifedipine therapy for preterm symptomatic placenta previa: A randomized, multicenter, double-blind, placebo-controlled trial.

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Eric Verspyck

Full Text Available To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding.PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis. Women were randomly allocated to receive either 20 mg of slow-release nifedipine three times daily (n = 54 or placebo (n = 55 until 36 + 6 weeks of gestation. The primary outcome for the trial was length of pregnancy measured in days after enrolment. Main secondary outcomes were rates of recurrent bleeding, cesarean delivery due to hemorrhage, blood transfusion, maternal side effects, gestational age at delivery and adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage > grade 2, perventricular leukomalacia > grade 1, or necrotizing enterocolitis. Analysis was by intention to treat.Mean (SD prolongation of pregnancy was not different between the nifedipine (n = 54 and the placebo (n = 55 group; 42.5 days ± 23.8 versus 44.2 days ± 24.5, p = 0.70. Cesarean due to hemorrhage performed before 37 weeks occurred more frequently in the nifedipine group in comparison with the placebo group (RR, 1.66; 95% confidence interval, 1.05-2.72. Adverse perinatal outcomes were comparable between groups; 3.8% for nifedipine versus 5.5% for placebo (relative risk, 0.52; 95% confidence interval 0.10-2.61. No maternal mortality or perinatal death occurred.Maintenance oral nifedipine neither prolongs duration of pregnancy nor improves maternal or perinatal outcomes.ClinicalTrials.gov NCT00620724.

Estimated medical cost reductions for paliperidone palmitate vs placebo in a randomized, double-blind relapse-prevention trial of patients with schizoaffective disorder.

Science.gov (United States)

Joshi, K; Lin, J; Lingohr-Smith, M; Fu, D J

2015-01-01

The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder. Rates of psychotic, depressive, and/or manic relapses and serious and non-serious treatment-emergent adverse events (TEAEs) were obtained from the long-term paliperidone palmitate vs placebo relapse prevention study. The total annual medical cost for a relapse from a US payer perspective was obtained from published literature and the costs for serious and non-serious TEAEs were based on Common Procedure Terminology codes. Total annual medical cost differences for patients treated with PP1M vs placebo were then estimated. Additionally, one-way and Monte Carlo sensitivity analyses were conducted. Lower rates of relapse (-18.3%) and serious TEAEs (-3.9%) were associated with use of PP1M vs placebo as reported in the long-term paliperidone palmitate vs placebo relapse prevention study. As a result of the reduction in these clinical event rates, the total annual medical cost was reduced by $7140 per patient treated with PP1M vs placebo. One-way sensitivity analysis showed that variations in relapse rates had the greatest impact on the estimated medical cost differences (range: -$9786, -$4670). Of the 10,000 random cycles of Monte Carlo simulations, 100% showed a medical cost difference schizoaffective disorder was associated with a significantly lower rate of relapse and a reduction in medical costs compared to placebo. Further evaluation in the real-world setting is warranted.

Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial.

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Babl, Franz E; Mackay, Mark T; Borland, Meredith L; Herd, David W; Kochar, Amit; Hort, Jason; Rao, Arjun; Cheek, John A; Furyk, Jeremy; Barrow, Lisa; George, Shane; Zhang, Michael; Gardiner, Kaya; Lee, Katherine J; Davidson, Andrew; Berkowitz, Robert; Sullivan, Frank; Porrello, Emily; Dalziel, Kim Marie; Anderson, Vicki; Oakley, Ed; Hopper, Sandy; Williams, Fiona; Wilson, Catherine; Williams, Amanda; Dalziel, Stuart R

2017-02-13

Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial. We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

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Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

2015-09-01

Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant