A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

Science.gov (United States)

Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

2007-09-01

Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled, dose-ranging Study.

Science.gov (United States)

Stohl, William; Merrill, Joan T; McKay, James D; Lisse, Jeffrey R; Zhong, Z John; Freimuth, William W; Genovese, Mark C

2013-05-01

To evaluate the efficacy/safety of belimumab in patients with rheumatoid arthritis (RA). Patients fulfilling American College of Rheumatology (ACR) criteria for RA for ≥ 1 year who had at least moderate disease activity while receiving stable disease-modifying antirheumatic drug (DMARD) therapy and failed ≥ 1 DMARD were randomly assigned to placebo or belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28, and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional 24-week extension (n = 237) in which all patients received belimumab. Primary efficacy endpoint was the Week 24 ACR20 response. Week 24 ACR20 responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p = 0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking any belimumab dose who continued with belimumab in the open-label extension had an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks was seen in patients taking placebo who switched in the extension to belimumab 10 mg/kg. Greater response rates were observed in patients who at baseline were rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor necrosis factor inhibitor-naive, or had elevated C-reactive protein levels, Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858 ng/ml). Adverse event rates were similar across treatment groups. In this phase II trial, belimumab demonstrated efficacy and was generally well tolerated in patients with RA who had failed previous therapies. [ClinicalTrials.gov identifier NCT00071812].

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

Science.gov (United States)

Naseri, Mohammad Hassan; Madani, Hoda; Ahmadi Tafti, Seyed Hossein; Moshkani Farahani, Maryam; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Hossein Ahmadi, Zargham; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharafi, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Fattah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdol Hosein; Baharvand, Hossein; Aghdami, Nasser

2018-07-01

The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the

Effect of green tea catechins in patients with high-grade prostatic intraepithelial neoplasia: Results of a short-term double-blind placebo controlled phase II clinical trial

Directory of Open Access Journals (Sweden)

Salvatore Micali

2017-10-01

Full Text Available Background and study objective: Several studies suggest a protective role of green tea catechins against prostate cancer (PCa. In order to evaluate the efficacy of green tea catechins for chemoprevention of PCa in patients with high-grade prostate intraepithelial neoplasia (HG-PIN we performed a phase II clinical trial. Methods: Sixty volunteers with HG-PIN were enrolled to carry out a double-blind randomized placebo-controlled phase II clinical trial. Treated group took daily 600 mg of green tea catechins (Categ Plus® for 1 year. Patients were screened at 6 and 12 months through prostatic biopsy and measurements of prostate-specific antigen (PSA. Results: Despite the statistically significant reduction of PSA observed in subjects who received green tea catechins for 6 and 12 months, we did not find any statistical difference in PCa incidence between the experimental groups neither after 6 nor after 12 months. However, throughout the one-year follow- up we observed very limited adverse effects induced by green tea catechins and a not significant improvement in lower urinary tract symptoms and quality of life. Conclusions: Although the small number of patients enrolled in our study and the relatively short duration of intervention, our findings seems to deny the efficacy of green tea catechins. However, results of our clinical study, mainly for its low statistical strength, suggest that the effectiveness of green tea catechins should be evaluated in both a larger cohort of men and longer trial.

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.

Science.gov (United States)

Lugo, James P; Saiyed, Zainulabedin M; Lau, Francis C; Molina, Jhanna Pamela L; Pakdaman, Michael N; Shamie, Arya Nick; Udani, Jay K

2013-10-24

UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

Science.gov (United States)

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

International Nuclear Information System (INIS)

Kim, Jisun; Kim, Lee Su; Han, Sehwan; Nam, Seok Jin; Kang, Han-Sung; Kim, Seung Il; Yoo, Young Bum; Jeong, Joon; Kim, Tae Hyun; Kang, Taewoo; Kim, Sung-Won; Lim, Woosung; Jung, Yongsik; Lee, Jeong Eon; Kim, Ku Sang; Yu, Jong-Han; Chae, Byung Joo; Jung, So-Youn; Kang, Eunyoung; Choi, Su Yun; Moon, Hyeong-Gon; Noh, Dong-Young; Kim, Eun-Kyu; Han, Wonshik; Kim, Min-Kyoon; Paik, Nam-Sun; Jeong, Sang-Seol; Yoon, Jung-han; Park, Chan Heun; Ahn, Sei Hyun

2014-01-01

Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. ClinicalTrials.gov Identifier http://clinicaltrial.gov/ct2/show/NCT01589367?term

Silver Biocide Analysis & Control Device, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Rapid, accurate measurement and process control of silver ion biocide concentrations in future space missions is needed. The purpose of the Phase II program is to...

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

Science.gov (United States)

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-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash.

Science.gov (United States)

Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole; Overgaard, Jens; Pfeiffer, Per

2017-07-01

Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated the effect of a vitamin K3 cream on cetuximab-induced rash. Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m 2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream and placebo were applied twice daily on two separate areas of the skin of minimum 10 × 10 cm for up to 2 months. Papulopustular eruptions were evaluated clinically and monitored by clinical photos. Skin biopsies, from ten patients taken before and after 1 month of treatment from each treatment area, were stained for EGFR and pEGFR. Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed in the skin of the vitamin K3-treated area compared to the placebo area. The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash.

Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study.

Science.gov (United States)

Lugo, James P; Saiyed, Zainulabedin M; Lane, Nancy E

2016-01-29

Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC). One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method. At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups. UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted. CTRI/2013/05/003663 ; CTRI/2013/02/003348 .

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

Science.gov (United States)

López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

2018-06-01

Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

Science.gov (United States)

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy

Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II.

Science.gov (United States)

Versyck, Barbara; van Geffen, Geert-Jan; Van Houwe, Patrick

2017-08-01

The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. A prospective randomized double blind placebo-controlled study. A secondary hospital. 140 breast cancer stage 1-3 patients undergoing mastectomy or tumorectomy with sentinel node or axillary node dissection. Patients were randomized to receive either a Pecs block with levobupivacaine 0.25% (n=70) or placebo block with saline (n=70). The pain levels were evaluated by Numeric Rating Scale (NRS) pain scores at 15-minute intervals during the post anesthesia care unit stay time (PACU), at 2-hour intervals for the first 24h on the ward and at 4-hour intervals for the next 24h. Intraoperative and postoperative opioid consumption were recorded during the full stay. Patient satisfaction was evaluated upon discharge using a 10-point scale. Intraoperative sufentanil requirements were comparable for the Pecs and placebo group (8.0±3.5μg and 7.8±3.0μg, P=0.730). Patients in the Pecs group experienced significantly less pain than patients in the control group (P=0.048) during their PACU stay. Furthermore, patients in the Pecs group required significant less postoperative opioids (9.16±10.15mg and 14.97±14.38mg morphine equivalent, P=0.037) and required significant fewer postsurgical opioid administration interventions than patients in the control group (P=0.045). Both patient-groups were very satisfied about their management (9.6±0.6 and 9.1±1.8 on a 10-point scale, P=0.211). The Pecs block reduces postsurgical opioid consumption during the PACU stay time for patients undergoing breast surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

Science.gov (United States)

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.

Lanthanum carbonate versus placebo for management of hyperphosphatemia in patients undergoing peritoneal dialysis: a subgroup analysis of a phase 2 randomized controlled study of dialysis patients

Directory of Open Access Journals (Sweden)

Hutchison Alastair J

2013-02-01

Full Text Available Abstract Background This short-term study assessed the efficacy and safety of lanthanum carbonate in the treatment of hyperphosphatemia in dialysis patients; here, we report a prespecified subgroup analysis of patients undergoing peritoneal dialysis. Methods Men and women (n = 39 who had received continuous ambulatory peritoneal dialysis for chronic kidney disease for 6 months or more were enrolled in eight renal medicine departments in the United Kingdom. A 2-week washout period was followed by a 4-week dose-titration phase during which patients received lanthanum carbonate titrated up to 2250 mg/day. This was followed by a 4-week, randomized, placebo-controlled, parallel-group phase during which patients continued to receive either lanthanum carbonate at the titrated dose, or a matched dose of placebo. The main outcome measure was control of serum phosphate levels (1.3-1.8 mmol/l at the end of the parallel-group phase. Results Serum phosphate was controlled in 3/39 (8% patients at the beginning of the dose-titration phase (after washout and in 18/31 (58% patients treated with lanthanum carbonate at its end. After the parallel-group phase, 60% of lanthanum carbonate-treated patients and 10% of those receiving placebo had controlled serum phosphate. There was no difference in mean (95% confidence interval serum phosphate levels between groups at randomization: lanthanum carbonate, 1.57 (1.34-1.81 mmol/l; placebo, 1.58 (1.40-1.76 mmol/l (p = 0.96. However, a difference was seen at the end of the parallel-group phase: lanthanum carbonate, 1.56 (1.33-1.79 mmol/l; placebo, 2.25 (1.81-2.68 mmol/l (p = 0.0015. There were no clinically important changes in nutritional parameters and no serious treatment-related adverse events were recorded. Conclusions At doses up to 2250 mg/day, lanthanum carbonate is well tolerated and controls hyperphosphatemia effectively. Treatment with higher doses of lanthanum carbonate may allow patients undergoing

Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock.

Science.gov (United States)

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.

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/.

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.

Science.gov (United States)

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

RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis.

Science.gov (United States)

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.

Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash

DEFF Research Database (Denmark)

Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole

2017-01-01

PURPOSE: Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated...... the effect of a vitamin K3 cream on cetuximab-induced rash. MATERIALS AND METHODS: Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream...... stained for EGFR and pEGFR. RESULTS: Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed...

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

Science.gov (United States)

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.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial

NARCIS (Netherlands)

van der Bom, Teun; Winter, Michiel M.; Bouma, Berto J.; Groenink, Maarten; Vliegen, Hubert W.; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Roos-Hesselink, Jolien W.; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

2013-01-01

The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a

Pressure Controlled Heat Pipe for Precise Temperature Control, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The principal Phase II objective is to refine and further develop the prototype PCHP into a useful thermal management tool. The Phase I program established the...

Coordinated Control of Multi-Agent Systems in Rapidly Varying Environments, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The main objective of this Phase II STTR project is to develop advanced control algorithms that enable multiple autonomous agents to perform complex tasks in rapidly...

Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

Science.gov (United States)

Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

2013-07-15

Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

Science.gov (United States)

de Diego-Otero, Yolanda; Calvo-Medina, Rocio; Quintero-Navarro, Carolina; Sánchez-Salido, Lourdes; García-Guirado, Francisco; del Arco-Herrera, Ignacio; Fernández-Carvajal, Isabel; Ferrando-Lucas, Teresa; Caballero-Andaluz, Rafaela; Pérez-Costillas, Lucia

2014-09-03

Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. A phase II randomized, double-blind pilot clinical trial. male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study.

Science.gov (United States)

Howard, James F; Utsugisawa, Kimiaki; Benatar, Michael; Murai, Hiroyuki; Barohn, Richard J; Illa, Isabel; Jacob, Saiju; Vissing, John; Burns, Ted M; Kissel, John T; Muppidi, Srikanth; Nowak, Richard J; O'Brien, Fanny; Wang, Jing-Jing; Mantegazza, Renato

2017-12-01

Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators

Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study.

Science.gov (United States)

Cazzola, M; Antivalle, M; Sarzi-Puttini, P; Dell'Acqua, D; Panni, B; Caruso, I

2000-01-01

To evaluate the efficacy of oral chicken type II collagen (CII) in the treatment of rheumatoid arthritis (RA). Sixty patients with clinically active RA of long duration (mean 7.2 +/- 5.5 years) were treated for 6 months with oral chicken CII at 0.25 mg/day (n = 31) or with placebo (n = 29) in a double-blind randomized study. The response rate to treatment of the collagen-treated group, based on the ACR 20% criteria, was higher than that of the control group but this difference was not statistically significant at any time. Intention-to-treat (ITT) analysis did not show statistically significant improvement in any of the several secondary outcome measures over the 6 months of the study in the collagen-treated patients in comparison with the placebo-treated group. However, in 2 collagen-treated patients we observed a clinical remission according to the criteria of the American Rheumatism Association. Our study seems to show that the oral treatment of RA patients with chicken CII is ineffective and results in only small and inconsistent benefits. Furthermore, our results raise the possibility that in a sub-group of patients oral collagen administration, usually considered devoid of harmful effects, may actually induce disease flares.

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

Science.gov (United States)

Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

2014-01-01

Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are

Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

Science.gov (United States)

Geisthoff, Urban W; Seyfert, Ulrich T; Kübler, Marcus; Bieg, Birgitt; Plinkert, Peter K; König, Jochem

2014-09-01

Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright © 2014 Elsevier Ltd. All rights reserved.

The efficacy and safety of S-flurbiprofen plaster in the treatment of knee osteoarthritis: a phase II, randomized, double-blind, placebo-controlled, dose-finding study

Directory of Open Access Journals (Sweden)

Yataba I

2017-04-01

not different across all four groups, and no severe AEs were observed. Conclusion: Clinically relevant pain relief was observed in all groups including placebo. Especially 40 mg showed remarkable pain relief in not only primary endpoint but also all the other endpoint with significant differences over placebo. The safety profile of SFPP 40 mg was not different from that of placebo. Therefore, 40 mg was determined as the optimal tested dose. Keywords: nonsteroidal anti-inflammatory drugs, patch, double-blind, visual analog scale, topical, optimal dose, randomized controlled trial

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. II. Comparison between parameters assessing the efficacy of immunotherapy.

Science.gov (United States)

Bousquet, J; Maasch, H; Martinot, B; Hejjaoui, A; Wahl, R; Michel, F B

1988-09-01

Specific immunotherapy is effective in alleviating symptoms in grass pollen-induced rhinitis, but there are no clear data demonstrating a correlation between symptom-medication scores and objective parameters. Twenty-five patients taking part in a double-blind, placebo-controlled immunotherapy with mixed grass pollen-formalinized allergoids were studied. All patients had the same investigations. Symptom-medication scores were significantly (p less than 0.005, Mann-Whitney U test) reduced in the treated group by comparison to the placebo-treated patients. Nasal challenges performed with threefold increasing numbers of orchard grass-pollen grains demonstrated that patients treated with allergoid tolerated a significantly (p less than 0.005, Wilcoxon W test) greater number of grains after treatment, whereas there was no mean difference in the placebo-treated patients. There was a significant (p less than 0.005, Spearman rank-correlation) correlation between nasal challenges and symptom scores during the season. The skin prick test end point was significantly (p less than 0.001, Wilcoxon W test) reduced after treatment in the allergoid-treated group and remained unchanged in the placebo-treated group. There was a significant (p less than 0.001) correlation between the skin prick test end point and symptom scores during the season. Serum grass-pollen IgG titrated by a solid-phase radioimmunoassay with Staphylococcus A protein was significantly (p less than 0.01, Wilcoxon W test) increased after treatment with allergoid, but there was no significant correlation between IgG titer and symptom scores during the season. Serum grass-pollen IgE increased (p less than 0.04, Wilcoxon W test) in the treated group but there was no correlation with symptom scores.

Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

International Nuclear Information System (INIS)

Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

2009-01-01

Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

Science.gov (United States)

Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

2009-06-15

Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial

Directory of Open Access Journals (Sweden)

Pérol David

2012-12-01

Full Text Available Abstract Background Chemotherapy induced nausea and vomiting (CINV remains a major problem that seriously impairs the quality of life (QoL in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens. Methods Chemotherapy-naïve patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness or the matching placebo (NCT00409071 clinicaltrials.gov. The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA and investigator recording (NCI-CTC AE V3.0 and treatment compliance. Results From September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C and 217 to placebo (P. Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility

Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study.

Science.gov (United States)

Koram, Kwadwo A; Adu, Bright; Ocran, Josephine; Karikari, Yaa S; Adu-Amankwah, Susan; Ntiri, Michael; Abuaku, Benjamin; Dodoo, Daniel; Gyan, Ben; Kronmann, Karl C; Nkrumah, Francis

2016-01-01

The erythrocyte binding antigen region II (EBA-175 RII) is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg) of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline). The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended. ClinicalTrials.gov. Identifier: NCT01026246.

Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study.

Directory of Open Access Journals (Sweden)

Kwadwo A Koram

Full Text Available The erythrocyte binding antigen region II (EBA-175 RII is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline. The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended.ClinicalTrials.gov. Identifier: NCT01026246.

A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.

Science.gov (United States)

Wallace, Daniel J; Stohl, William; Furie, Richard A; Lisse, Jeffrey R; McKay, James D; Merrill, Joan T; Petri, Michelle A; Ginzler, Ellen M; Chatham, W Winn; McCune, W Joseph; Fernandez, Vivian; Chevrier, Marc R; Zhong, Z John; Freimuth, William W

2009-09-15

To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score >/=4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer >/=1:80 and/or anti-double-stranded DNA [anti-dsDNA] >/=30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

International Nuclear Information System (INIS)

Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

2005-01-01

Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding

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

Directory of Open Access Journals (Sweden)

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.

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,

Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.

Science.gov (United States)

Sun, Hong; Dodick, David W; Silberstein, Stephen; Goadsby, Peter J; Reuter, Uwe; Ashina, Messoud; Saper, Joel; Cady, Roger; Chon, Yun; Dietrich, Julie; Lenz, Robert

2016-04-01

The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was -3·4 (SE 0·4) days with AMG 334 70 mg versus -2·3 (0·3) days with placebo (difference -1·1 days [95% CI -2·1 to -0·2], p=0·021). The mean reductions in monthly migraine days with the 7 mg (-2·2 [SE 0·4]) and the 21 mg (-2·4 [0·4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54

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...

A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia

Directory of Open Access Journals (Sweden)

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

Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.

Directory of Open Access Journals (Sweden)

Eiichiro Nagata

Full Text Available Bromocriptine mesylate (BRC, a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS Here we report a first in human trial in ALS.A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7. The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint and upon completion or discontinuation of the study (2nd endpoint of the dosing.Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%, eating and drinking (P = 2.2%, ALSFRS-R total (P = 17.6%, grip strength (P = 19.8% compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%, ALSAQ40-communication (P = 11.9%, eating and drinking (P = 13.6%, and neck forward-bent test (P = 15.4% of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.UMIN Clinical Trials UMIN000008527.

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

Science.gov (United States)

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.

Small Business Innovation Research GRC Phase I, Phase II, and Post-Phase II Opportunity Assessment for 2015

Science.gov (United States)

Nguyen, Hung D.; Steele, Gynelle C.

2016-01-01

This report outlines the 2015 Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) Phase I, Phase II, and Post-Phase II opportunity contract award results associated with NASA's Aeronautics Research Mission Directorate (ARMD), Human Exploration and Operations Mission Directorate (HEOMD), Science Mission Directorate (SMD), and Space Technology Mission Directorate (STMD) for NASA Glenn Research Center. The report also highlights the number of Phase I, Phase II, and Post-Phase II contracts awarded by mission directorate. The 2015 Phase I contract awards to companies in Ohio and their corresponding technologies are also discussed.

Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed.

Science.gov (United States)

Hurwitz, Herbert I; Uppal, Nikhil; Wagner, Stephanie A; Bendell, Johanna C; Beck, J Thaddeus; Wade, Seaborn M; Nemunaitis, John J; Stella, Philip J; Pipas, J Marc; Wainberg, Zev A; Manges, Robert; Garrett, William M; Hunter, Deborah S; Clark, Jason; Leopold, Lance; Sandor, Victor; Levy, Richard S

2015-12-01

Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer. In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation. In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation-based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%). Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation. © 2015 by American Society of Clinical Oncology.

Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study

Directory of Open Access Journals (Sweden)

Paulo Roberto Chizzola

2000-03-01

Full Text Available OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43±9 years, and their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016 as well as an increase in left ventricular shortening fraction (p=0.02 and in left ventricular ejection fraction (p=0.017 occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries.

Science.gov (United States)

Buvat, Jacques; Tesfaye, Fisseha; Rothman, Margaret; Rivas, David A; Giuliano, François

2009-04-01

Dapoxetine is being developed for the on-demand treatment of premature ejaculation (PE). Previous clinical trials have demonstrated its safety and efficacy. To evaluate the long-term efficacy and safety of dapoxetine in men with PE. This randomized, double-blind, parallel-group, placebo-controlled, phase 3 trial, conducted in 22 countries, enrolled men (N=1162) > or = 18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for > or = 6 mo, with an intravaginal ejaculatory latency time (IELT) or = 75% of intercourse episodes at baseline. Dapoxetine 30 mg or dapoxetine 60 mg or placebo on demand (1-3 h before intercourse) for 24 wk. Stopwatch-measured IELT, Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change, adverse events (AEs). The study was completed by 618 men. Mean average IELT increased from 0.9 min at baseline (all groups) to 1.9 min, 3.2 min, and 3.5 min with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively, at study end point; geometric mean IELT increased from 0.7 min at baseline to 1.1 min, 1.8 min, and 2.3 min, respectively, at study end point. All PEP measures and IELTs improved significantly with dapoxetine versus placebo at week 12 and week 24 (p<0.001 for all). The most common AEs were nausea, dizziness, diarrhea, and headache. AEs led to discontinuation in 1.3%, 3.9%, and 8.2% of subjects with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively. Limitations of this study included the exclusion of men who were not in long-term monogamous relationships. Dapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population.

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

Directory of Open Access Journals (Sweden)

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?

Science.gov (United States)

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.

Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

International Nuclear Information System (INIS)

Brose, Marcia S; Schlumberger, Martin; Nutting, Christopher M; Sherman, Steven I; Shong, Young Kee; Smit, Johannes WA; Reike, Gerhard; Chung, John; Kalmus, Joachim; Kappeler, Christian

2011-01-01

The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC. DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and

A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation

NARCIS (Netherlands)

Vincent, Jean-Louis; Ramesh, Mayakonda K.; Ernest, David; Larosa, Steven P.; Pachl, Jan; Aikawa, Naoki; Hoste, Eric; Levy, Howard; Hirman, Joe; Levi, Marcel; Daga, Mradul; Kutsogiannis, Demetrios J.; Crowther, Mark; Bernard, Gordon R.; Devriendt, Jacques; Puigserver, Joan Vidal; Blanzaco, Daniel U.; Esmon, Charles T.; Parrillo, Joseph E.; Guzzi, Louis; Henderson, Seton J.; Pothirat, Chaicharn; Mehta, Parthiv; Fareed, Jawed; Talwar, Deepak; Tsuruta, Kazuhisa; Gorelick, Kenneth J.; Osawa, Yutaka; Kaul, Inder

2013-01-01

Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

[Placebo-controlled trials in schizophrenia].

Science.gov (United States)

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

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.

Science.gov (United States)

Sirivichayakul, Chukiat; Barranco-Santana, Elizabeth A; Esquilin-Rivera, Inés; Oh, Helen M L; Raanan, Marsha; Sariol, Carlos A; Shek, Lynette P; Simasathien, Sriluck; Smith, Mary Kathryn; Velez, Ivan Dario; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

2016-05-15

A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mailjournals.permissions@oup.com.

Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

Science.gov (United States)

Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

2013-12-02

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All

Design of clinical trials Phase I and II with radiopharmaceuticals

International Nuclear Information System (INIS)

Giannone, C.A.; Soroa, V.E.

2015-01-01

We presented some usual designs for clinical studies in Phase I and Phase II. For Phase I we considered the 3 + 3 Classic design, designs with accelerated titration and those with dose escalation schemes with overdose control (EWOC). For Phase II designs with efficacy outcomes are presented. The design proposed by Fleming is discussed as well as those with inclusion of patients in two stages: Gehan’s design and the Optimal two–stage Simon’s design. We also discussed the design of combined endpoints of efficacy and safety of Bryant and Day with an application example of therapeutically Lu-177. Finally some proposals for phase II trials with control group are considered. (authors) [es

New fuzzy EWMA control charts for monitoring phase II fuzzy profiles

Directory of Open Access Journals (Sweden)

Ghazale Moghadam

2016-01-01

Full Text Available In many quality control applications, the quality of a process or product is explained by the relationship between response variable and one or more explanatory variables, called a profile. In this paper, a new fuzzy EWMA control chart for phase II fuzzy profile monitoring is proposed. To this end, we extend EWMA control charts to its equivalent Fuzzy type and then implement fuzzy ranking methods to determine whether the process fuzzy profile is under or out of control. The proposed method is capable of identifying small changes in process under condition of process profile explaining parameters vagueness, roughness and uncertainty. Determining the source of changes, this method provides us with the possibility of recognizing the causes of process transition from stable mode, removing these causes and restoring the process stable mode.

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

Directory of Open Access Journals (Sweden)

Klaus Reither

Full Text Available Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1 formulated with the adjuvant IC31, was evaluated in HIV-infected adults.HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay.47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015. Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells.H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response.Pan African Clinical Trials Registry (PACTR PACTR201105000289276.

Phase II and III the next generation of CLS beamline control and data acquisition systems

International Nuclear Information System (INIS)

Matias, E.; Beauregard, D.; Berg, R.; Black, G.; Boots, M.J.; Dolton, W.; Hunter, D.; Igarashi, R.; Liu, D.; Maxwell, D.; Miller, C.D.; Wilson, T.; Wright, G.

2012-01-01

The Canadian Light Source (CLS) is nearing the completion of its suite of Phase II Beamlines and in detailed design of its Phase III Beamlines. The paper presents an overview of the overall approach adopted by CLS in the development of beamline control and data acquisition systems. Building on the experience of our first phase of beamlines the CLS has continued to make extensive use of EPICS with EDM and QT based user interfaces. Increasing interpretive languages such as Python are finding a place in the beamline control systems. Web based environment such as ScienceStudio have also found a prominent place in the control system architecture as we move to tighter integration between data acquisition, visualization and data analysis. (authors)

Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.

Science.gov (United States)

Krug, Lee M; Kindler, Hedy L; Calvert, Hilary; Manegold, Christian; Tsao, Anne S; Fennell, Dean; Öhman, Ronny; Plummer, Ruth; Eberhardt, Wilfried E E; Fukuoka, Kazuya; Gaafar, Rabab M; Lafitte, Jean-Jacques; Hillerdal, Gunnar; Chu, Quincy; Buikhuisen, Wieneke A; Lubiniecki, Gregory M; Sun, Xing; Smith, Margaret; Baas, Paul

2015-04-01

Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102. From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%]). In this randomised trial, vorinostat given as a second-line or third

Implementation of a Novel Adherence Monitoring Strategy in a Phase III, Blinded, Placebo-Controlled, HIV-1 Prevention Clinical Trial.

Science.gov (United States)

Husnik, Marla J; Brown, Elizabeth R; Marzinke, Mark; Livant, Edward; Palanee-Phillips, Thesla; Hendrix, Craig W; Matovu Kiweewa, Flavia; Nair, Gonasagrie; Soto-Torres, Lydia E; Schwartz, Katie; Hillier, Sharon L; Baeten, Jared M

2017-11-01

Placebo-controlled HIV-1 prevention trials of pre-exposure prophylaxis (PrEP) have not generally used concurrent measurement of adherence because of the potential risk of unblinding. However, several pre-exposure prophylaxis trials for HIV-1 prevention among women failed to show effectiveness because of low product adherence. Evaluation of product adherence objectively during a study provides the opportunity for strengthening adherence activities at sites having low adherence. During MTN-020/ASPIRE, a phase III, placebo-controlled trial of the dapivirine intravaginal ring, we implemented an adherence monitoring system. Monitoring began in quarter 1 (Q1) 2013 and continued through the conclusion of the trial. Blood plasma was collected quarterly and tested for dapivirine concentrations while maintaining blinding among study team members involved in participant management. Dapivirine concentrations >95 pg/mL, reflecting >8 hours of continuous use, were assessed as signaling product use. Study leadership monitored results on a monthly basis and provided feedback to site investigators. Experiences were shared across sites to motivate staff and counsel participants to strive toward higher adherence levels. An upward trend in adherence was observed (P dapivirine >95 pg/mL increased from 63% in Q1 2013 to 84% by Q1 2015. Ongoing drug level testing as a marker of adherence in MTN-020/ASPIRE demonstrates the feasibility of real-time adherence monitoring while maintaining study blinding at the level of participants, sites, and study leadership. This approach is novel for large-scale effectiveness studies for HIV-1 prevention.

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

Directory of Open Access Journals (Sweden)

Maneeton Narong

2012-09-01

Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

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

Directory of Open Access Journals (Sweden)

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

Treatment of Plaque-Type Psoriasis With Oral CF101: Data from a Phase II/III Multicenter, Randomized, Controlled Trial.

Science.gov (United States)

David, Michael; Gospodinov, Dimitar Konstantinov; Gheorghe, Nicola; Mateev, Grisha Stefanov; Rusinova, Mariyana Venelinova; Hristakieva, Evgeniya; Solovastru, Laura Gheuca; Patel, Rita V; Giurcaneanu, Calin; Hitova, Mariela Chepileva; Purcaru, Anca Ioana; Horia, Beti; Tsingov, Iliya Iliev; Yankova, Rumyana Kaloferova; Kadurina, Miroslava Ilieva; Ramon, Michal; Rotaru, Maria; Simionescu, Olga; Benea, Vasile; Demerdjieva, Zdravka Velichkova; Cosgarea, Maria Rodica; Morariu, Horia Silviu; Michael, Ziv; Cristodor, Patricia; Nica, Carmen; Silverman, Michael H; Bristol, David R; Harpaz, Zivit; Farbstein, Motti; Cohen, Shira; Fishman, Pnina

2016-08-01

CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients. To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis. This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level. CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%). Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment. J Drugs Dermatol. 2016;15(8):931-938.

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III

Directory of Open Access Journals (Sweden)

Giuseppe Morgia

2017-06-01

Full Text Available Objective: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. Material and methods: From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A or treatment (Group B. Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95% and Calendula extract 80 mg (1 suppository/die for 1 month. Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT. Results: A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01, IIEF-5 (+ 3.5; p < 0.01, PEDT (-6.5; p < 0.01, peak flow (+2.8; p < 0.01 and VAS (-6.5; p < 0.01 with significant differences over placebo group (all p-value significant. Conclusions: In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

Science.gov (United States)

Morgia, Giuseppe; Russo, Giorgio Ivan; Urzì, Daniele; Privitera, Salvatore; Castelli, Tommaso; Favilla, Vincenzo; Cimino, Sebastiano

2017-06-30

The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers.

Science.gov (United States)

Choung, R S; Talley, N J; Peterson, J; Camilleri, M; Burton, D; Harmsen, W S; Zinsmeister, A R

2007-03-01

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.

Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

Science.gov (United States)

Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-07-01

A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd.

[Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study].

Science.gov (United States)

Milewicz, A; Gejdel, E; Sworen, H; Sienkiewicz, K; Jedrzejak, J; Teucher, T; Schmitz, H

1993-07-01

The efficacy of a Vitex agnus castus preparation (Strotan capsules) was investigated in a randomized double blind study vs. placebo. This clinical study involved 52 women with luteal phase defects due to latent hyperprolactinaemia. The daily dose was one capsule (20 mg) Vitex agnus castus preparation and placebo, respectively. Aim of the study was to prove whether the elevated pituitary prolactin reserve can be reduced and deficits in luteal phase length and luteal phase progesterone synthesis be normalized. Blood for hormonal analysis was taken at days 5-8 and day 20 of the menstrual cycle before and after three month of therapy. Latent hyperprolactinaemia was analysed by monitoring the prolactin release 15 and 30 min after i.v. injection of 200 micrograms TRH. 37 complete case reports (placebo: n = 20, verum: n = 17) after 3 month of therapy were statistically evaluated. The prolactin release was reduced after 3 months, shortened luteal phases were normalised and deficits in the luteal progesterone synthesis were eliminated. These changes were significant and occurred only in the verum group. All other hormonal parameters did not change with the exception of 17 beta-estradiol which rouse up in the luteal phase in patients receiving verum. Side effects were not seen, two women treated with the Vitex agnus castus preparation got pregnant. The tested preparation is thought to be an efficient medication in the treatment of luteal phase defects due to latent hyperprolactinaemia.

Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial.

Science.gov (United States)

Kil, Jonathan; Lobarinas, Edward; Spankovich, Christopher; Griffiths, Scott K; Antonelli, Patrick J; Lynch, Eric D; Le Prell, Colleen G

2017-09-02

Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Motokazu Kato

Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

Directory of Open Access Journals (Sweden)

Berk Michael

2012-08-01

Full Text Available Abstract Background N-acetyl cysteine (NAC is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149 had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493.

Safety and efficacy of MIM D3 ophthalmic solutions in a randomized placebo controlled Phase 2 clinical trial in patients with dry eye

Directory of Open Access Journals (Sweden)

Meerovitch K

2013-06-01

Full Text Available Karen Meerovitch,1 Gail Torkildsen,2 John Lonsdale,3 Heidi Goldfarb,4 Teresa Lama,1 Garth Cumberlidge,1 George W Ousler III5 1Mimetogen Pharmaceuticals Inc, Montreal, QC, Canada; 2Andover Eye Associates, Andover, MA, USA; 3Central Maine Eye Care, Lewiston, ME, USA; 4SDC, Tempe, AZ, USA; 5Ora Inc, Andover, MA, USA Purpose: To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye. Design: A prospective, two-center, randomized, double-masked, placebo-controlled Phase 2 study. Methods: A total of 150 dry eye patients were randomized 1:1:1 to study medication (1% MIM-D3, 5% MIM-D3, or placebo and dosed twice daily (BID for 28 days. Key eligibility criteria included exacerbation in corneal staining and ocular discomfort in the Controlled Adverse Environment (CAESM on two visits, separated by 1 week of BID dosing with artificial tears. Safety and efficacy were evaluated at baseline, throughout treatment, and for 2 weeks post-treatment. The pre-specified primary outcome measures were fluorescein corneal staining post-CAE at day 28 and diary worst symptom scores over 28 days. Secondary outcomes included the pre-, post-, and the change from pre- to post-CAE fluorescein and lissamine green staining in both corneal and conjunctival regions, as well as individual diary symptoms. Results: The prespecified primary endpoints were not met. Compared with placebo, fluorescein corneal staining at day 28 was significantly improved (P < 0.05 in the 1% MIM-D3 group for the assessment of change from pre-CAE to post-CAE. In addition, following CAE exposure, patients in the 1% MIM-D3 group showed significant improvements versus placebo (P < 0.05 in inferior fluorescein and lissamine green staining after 14 and 28 days. Compared with placebo, patients in the 5% MIM-D3 group reported significantly lower daily diary scores for ocular dryness (P < 0.05. In a subgroup defined by higher symptom scores during

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

Science.gov (United States)

Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

2015-09-01

Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in

Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study.

Science.gov (United States)

Hattori, Nobutaka; Takeda, Atsushi; Takeda, Shinichi; Nishimura, Akira; Kato, Masafumi; Mochizuki, Hideki; Nagai, Masahiro; Takahashi, Ryosuke

2018-04-27

Rasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. Patients aged 30-79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. In total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were -0.84 h (rasagiline 1 mg/day) and -0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: -1.27, -1.74, and -2.51 (0.5 mg/day) and -1.27, -2.14, and -3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). As an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

Science.gov (United States)

Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

2016-03-15

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Directory of Open Access Journals (Sweden)

Palacios Santiago

2010-06-01

Full Text Available Abstract Background We report the safety findings from a 3-year phase 3 study (NCT00205777 of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE reporting and routine physical, gynecologic, and breast examination. Results Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. Trial Registration Trial registration number: NCT00205777; Trial registration date: September 16, 2005

Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study

Science.gov (United States)

Paris, A; Gonnet, N; Chaussard, C; Belon, P; Rocourt, F; Saragaglia, D; Cracowski, J L

2008-01-01

Aims The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. Methods This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18–60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day−1. Results One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day−1 of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. Conclusions The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. What is already known about this subject The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. What this study adds The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH

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.

Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.

Science.gov (United States)

Lockley, Steven W; Dressman, Marlene A; Licamele, Louis; Xiao, Changfu; Fisher, Dennis M; Flynn-Evans, Erin E; Hull, Joseph T; Torres, Rosarelis; Lavedan, Christian; Polymeropoulos, Mihael H

2015-10-31

Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist. We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres. We screened totally blind adults (18-75 years of age), who were eligible for the randomisation phase of SET if they had a non-24-hour circadian period (τ) of 24·25 h or longer (95% CI greater than 24·0 and up to 24·9 h), as calculated from measurements of urinary 6-sulphatoxymelatonin rhythms. For SET, we used block randomisation to assign patients (1:1) to receive tasimelteon (20 mg) or placebo every 24 h at a fixed clock time 1 h before target bedtime for 26 weeks. Patients who entered the open-label group receiving tasimelteon in SET or who did not meet the SET inclusion criteria but did meet the RESET inclusion criteria were screened for RESET. A subset of the patients who entered the open-label group before the RESET study and who had eligible τ values were screened for RESET after completing the open-label treatment. In RESET, we withdrew tasimelteon in a randomised manner (1:1) in patients who responded (ie, entrained) after a tasimelteon run-in period. Entrainment was defined as having τ of 24·1 h or less and a 95% CI that included 24·0 h. In SET, the primary endpoint was the proportion of entrained patients, assessed in the intention-to-treat population. The planned step-down primary endpoint assessed the proportion of patients who had a clinical response (entrainment at month 1 or month 7 plus clinical improvement, measured by the Non-24 Clinical Response Scale). In RESET, the primary endpoint was the proportion of non

PEP-II injection timing and controls

International Nuclear Information System (INIS)

Bharadwaj, V.; Browne, M.; Crane, M.; Gromme, T.; Himel, T.; Ross, M.; Stanek, M.; Ronan, M.

1997-07-01

Hardware has been built and software written and incorporated in the existing SLC accelerator control system to control injection of beam pulses from the accelerator into the PEP-II storage rings currently under construction. Hardware includes a CAMAC module to delay the machine timing fiducial in order that a beam pulse extracted from a damping ring will be injected into a selected group of four 476 MHz buckets in a PEP-II ring. Further timing control is accomplished by shifting the phase of the bunches stored in the damping rings before extraction while leaving the phase of the PEP-II stored beam unchanged. The software which drives timing devices on a pulse-to-pulse basis relies on a dedicated communication link on which one scheduling microprocessor broadcasts a 128-bit message to all distributed control microprocessors at 360 Hz. PEP-II injection will be driven by the scheduling microprocessor according to lists specifying bucket numbers in arbitrary order, and according to scheduling constraints maximizing the useful beam delivered to the SLC collider currently in operation. These lists will be generated by a microprocessor monitoring the current stored per bucket in each of the PEP-II rings

Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

2015-12-03

This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in

Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

Science.gov (United States)

Elewski, Boni E; Okun, Martin M; Papp, Kim; Baker, Christopher S; Crowley, Jeffrey J; Guillet, Gérard; Sundaram, Murali; Poulin, Yves; Gu, Yihua; Geng, Ziqian; Williams, David A; Rich, Phoebe A

2018-01-01

Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P psoriasis versus with placebo and no new safety risks were identified. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Effect of Daikenchuto, a Traditional Japanese Herbal Medicine, after Total Gastrectomy for Gastric Cancer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

Science.gov (United States)

Yoshikawa, Kozo; Shimada, Mitsuo; Wakabayashi, Go; Ishida, Koichiro; Kaiho, Takashi; Kitagawa, Yuko; Sakamoto, Junichi; Shiraishi, Norio; Koeda, Keisuke; Mochiki, Erito; Saikawa, Yoshiro; Yamaguchi, Kazuya; Watanabe, Masayuki; Morita, Satoshi; Kitano, Seigo; Saji, Shigetoyo; Kanematsu, Takashi; Kitajima, Masaki

2015-08-01

Daikenchuto (DKT) has widely been used to improve abdominal symptoms by being expected to accelerate bowel motility. The purpose of this study is to examine the efficacy and safety of DKT for prevention of ileus and associated gastrointestinal symptoms after total gastrectomy. Two hundred and forty-five gastric cancer patients who underwent total gastrectomy were enrolled. Patients received either DKT (15.0 g/d) or matching placebo from postoperative days 1 to 12. Primary end points were time to first flatus, time to first bowel movement (BM), and frequency of BM. Secondary end points included quality of life, C-reactive protein level, symptoms indicative of a severe gastrointestinal disorder, and incidence of postoperative ileus. A total of 195 patients (DKT, n = 96; placebo, n = 99) were included in the per-protocol set analysis. There were no significant differences between the groups in terms of patient background characteristics. Median time to first BM was shorter in the DKT group than in the placebo group (94.7 hours vs 113.9 hours; p = 0.051). In patients with high medication adherence, median time to first BM was significantly shorter in the DKT group than in the placebo group (93.8 hours vs 115.1 hours; p = 0.014). Significantly fewer patients in the DKT group had ≥2 symptoms of gastrointestinal dysfunction than those in the placebo group on postoperative day 12 (p = 0.026). Administration of DKT during the immediate postoperative period after total gastrectomy appears to promote early recovery of postoperative bowel function. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

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.

COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

Science.gov (United States)

Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

2017-12-01

Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials

Directory of Open Access Journals (Sweden)

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.

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study.

Science.gov (United States)

Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

2014-02-01

Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm(-2) ) or placebo injections into their SMF at up to four treatment sessions ~28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm(-2) , respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS; P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS; P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. ATX-101 was effective and well tolerated for nonsurgical SMF reduction. © 2013 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

KIT/KPS of Qinshan phase-II and a discussion on integrated information management and automatic control

International Nuclear Information System (INIS)

Yan Changhui

2001-01-01

Centralized Data Processing and Safety Panel (KIT/KPS) of Qinshan Phase-II power project is described, and the necessity and engineering scheme is presented of integrated information management and automatic control that would achieve in power plant according to the technology scheme and technology trait of KIT/KPS

The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study.

Science.gov (United States)

Bagel, Jerry; Duffin, Kristina Callis; Moore, Angela; Ferris, Laura K; Siu, Kimberly; Steadman, Jennifer; Kianifard, Farid; Nyirady, Judit; Lebwohl, Mark

2017-10-01

Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis. Evaluate the efficacy and safety of secukinumab in moderate-to-severe scalp psoriasis. In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12. At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator's Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Long-term efficacy of modified-release recombinant human TSH (MRrhTSH) augmented radioiodine (131I) therapy for benign multinodular goiter. Results from a multicenter international, randomized, placebo-controlled dose-selection study

DEFF Research Database (Denmark)

Fast, Søren; Hegedus, Laszlo; Pacini, Furio

2014-01-01

with 131I-therapy. Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2±9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 ml (31.9 - 242.2 ml)) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30) or 0.03 mg MRrhTSH (n=33), 24 hours before...... a calculated 131I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by CT-scan) at baseline, month 6 and month 36. Thyroid function and quality of life (QoL) was evaluated at 3 month and yearly intervals, respectively. Results: At 6 months, TV reduction...... was enhanced in the 0.03 mg MRrhTSH group (32.9% versus 23.1% in the placebo group, p=0.03), but not in the 0.01 mg MRrhTSH group. At month 36 the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH-group and 53 ± 18.6% in the 0.03 mg MRrh...

[Randomized double-blind comparative study of minaprine (200mg/j) and of placebo on memory loss].

Science.gov (United States)

Allain, H; Belliard, S; Lieury, A; Menard, G; Patat, A; Le Coz, F; Gandon, J M

1996-01-01

Thirty five subjects (age: 45-69 years) with subjective memory loss, without any other neuropsychiatric or somatic disease, were recruited in a phase II study. This double blind randomized versus placebo controlled study compared the effects of minaprine (200 mg/d) with placebo, in two parallel groups, during 2 months, on memory, attention and vigilance. Three psychometric tests were the main criteria of assessment: a standardized battery of memory tests (SM 5), the dual-coding test, the analysis of choice reaction times (CRT) and the critical flicker fusion point (CFF). A positive effect of minaprine was detected on words delayed recall (p = 0.028) and immediate recognition of words (p = 0.049). The global clinical tests (CGI, MacNair scale) were not statistically modified. Tolerability of minaprine and placebo were comparable. A positive pharmacodynamic activity on mnemonic performance is thus demonstrated in favour of minaprine (200 mg/d) in this specific population characterized by a memory complaint. These results would lead to a phase III study in which the main criteria would be global scales in order to confirm the clinical reliability of the present results.

Adaptive designs for dose-finding in non-cancer phase II trials: influence of early unexpected outcomes.

Science.gov (United States)

Resche-Rigon, Matthieu; Zohar, Sarah; Chevret, Sylvie

2008-01-01

In non-cancer phase II trials, dose-finding trials are usually carried out using fixed designs, in which several doses including a placebo are randomly distributed to patients. However, in certain vulnerable populations, such as neonates or infants, there is an heightened requirement for safety, precluding randomization. To estimate the minimum effective dose of a new drug from a non-cancer phase II trial, we propose the use of adaptive designs like the Continual Reassessment Method (CRM). This approach estimates the dose closest to some target response, and has been shown to be unbiased and efficient in cancer phase I trials. Based on a motivating example, we point out the individual influence of first outliers in this setting. A weighted version of the CRM is proposed as a theoretical benchmark to control for these outliers. Using simulations, we illustrate how this approach provides further insight into the behavior of the CRM. When dealing with low targets like a 10% failure rate, the CRM appears unable to rapidly overcome an early unexpected outcome. This behavior persisted despite changing the inference (Bayesian or likelihood), underlying dose-response model (though slightly improved using the power model), and the number of patients enrolled at each dose level. The choices for initial guesses of failure rates, the vague prior for the model parameter, and the log-log shape of weights can appear somewhat arbitrary. In phase II dose-finding studies in which failure targets are below 20%, the CRM appears quite sensitive to first unexpected outcomes. Using a power model for dose-response improves some behavior if the trial is started at the first dose level and includes at least three to five patients at the starting dose before applying the CRM allocation rule.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

NARCIS (Netherlands)

Lawlor, B.; Kennelly, S.; O'Dwyer, S.; Cregg, F.; Walsh, C.; Coen, R.; Kenny, R.A.; Howard, R.; Murphy, C.; Adams, J.; Daly, L.; Segurado, R.; Gaynor, S.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Wallin, A.; Borjesson, A.; Molloy, W.; Tsolaki, M.; Olde Rikkert, M.G.M.

2014-01-01

INTRODUCTION: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol

International Nuclear Information System (INIS)

Martinez, Jessica A.; Chalasani, Pavani; Thomson, Cynthia A.; Roe, Denise; Altbach, Maria; Galons, Jean-Philippe; Stopeck, Alison; Thompson, Patricia A.; Villa-Guillen, Diana Evelyn; Chow, H-H. Sherry

2016-01-01

Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a

Serum biomarkers as predictors of long-term outcome in severe traumatic brain injury: analysis from a randomized placebo-controlled Phase II clinical trial.

Science.gov (United States)

Raheja, Amol; Sinha, Sumit; Samson, Neha; Bhoi, Sanjeev; Subramanian, Arulselvi; Sharma, Pushpa; Sharma, Bhawani Shankar

2016-09-01

OBJECTIVE There has been increased interest in the potential importance of biochemical parameters as predictors of outcome in severe traumatic brain injury (sTBI). METHODS Of 107 patients with sTBI (age 18-65 years with a Glasgow Coma Scale score of 4-8 presenting within 8 hours after injury) who were randomized for a placebo-controlled Phase II trial of progesterone with or without hypothermia, the authors serially analyzed serum biomarkers (S100-B, glial fibrillary acidic protein [GFAP], neuron-specific enolase [NSE], tumor necrosis factor-α, interleukin-6 [IL-6], estrogen [Eg], and progesterone [Pg]). This analysis was performed using the sandwich enzyme-linked immunosorbent assay technique at admission and 7 days later for 86 patients, irrespective of assigned group. The long-term predictive values of serum biomarkers for dichotomized Glasgow Outcome Scale (GOS) score, functional independence measure, and survival status at 6 and 12 months were analyzed using an adjusted binary logistic regression model and receiver operating characteristic curve. RESULTS A favorable GOS score (4-5) at 1 year was predicted by higher admission IL-6 (above 108.36 pg/ml; area under the curve [AUC] 0.69, sensitivity 52%, and specificity 78.6%) and Day 7 Pg levels (above 3.15 ng/ml; AUC 0.79, sensitivity 70%, and specificity 92.9%). An unfavorable GOS score (1-3) at 1 year was predicted by higher Day 7 GFAP levels (above 9.50 ng/ml; AUC 0.82, sensitivity 78.6%, and specificity 82.4%). Survivors at 1 year had significantly higher Day 7 Pg levels (above 3.15 ng/ml; AUC 0.78, sensitivity 66.7%, and specificity 90.9%). Nonsurvivors at 1 year had significantly higher Day 7 GFAP serum levels (above 11.14 ng/ml; AUC 0.81, sensitivity 81.8%, and specificity 88.9%) and Day 7 IL-6 serum levels (above 71.26 pg/ml; AUC 0.87, sensitivity 81.8%, and specificity 87%). In multivariate logistic regression analysis, independent predictors of outcome at 1 year were serum levels of Day 7 Pg (favorable

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

Science.gov (United States)

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.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

Science.gov (United States)

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 and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: a phase II clinical trial.

Science.gov (United States)

Glina, Sidney; Toscano, Iderpol; Gomatzky, Celso; de Góes, Plínio Moreira; Júnior, Archimedes Nardozza; Claro, Joaquim Francisco de Almeida; Pagani, Eduardo

2009-02-01

Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (ANOVA P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated.

Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study.

Science.gov (United States)

Weil, E H; Eerdmans, P H; Dijkman, G A; Tamussino, K; Feyereisl, J; Vierhout, M E; Schmidbauer, C; Egarter, C; Kölle, D; Plasman, J E; Heidler, H; Abbühl, B E; Wein, W

1998-01-01

Midodrine is a potent and selective alpha1-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. The aim of this randomized double-blind placebo-controlled multicenter study was to evaluate the efficacy and safety of midodrine for the treatment of stress urinary incontinence. The primary criterion of efficacy was the maximum urethral closure pressure at rest. Voiding diaries, symptom and incontinence questionnaires and patient/investigator global assessment were also used to evaluate its efficacy. After 4 weeks of treatment no significant changes in MUCP were found. The global assessment by the patient and investigator did indicate that patients on active treatment had a more positive assessment than the placebo group. In conclusion, midodrine did not cause significant improvements in urodynamic parameters, but there were subjective improvements in some of the patients in the treated groups. Furthermore midodrine was well tolerated.

Efficacy of Wobe-Mugos registered E for reduction of oral mucositis after radiotherapy. Results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study

International Nuclear Information System (INIS)

Doerr, W.; Herrmann, T.

2007-01-01

Purpose: To investigate the efficacy and safety of Wobe-Mugos registered E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis. Patients and Methods: The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos registered E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. Results: Wobe-Mugos registered E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos registered E group. Conclusion: The present study failed to demonstrate any effect of treatment with Wobe-Mugos registered E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis. (orig.)

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

Science.gov (United States)

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 steerable/distance enhanced penetrometer delivery system: Phase II. Topical report

International Nuclear Information System (INIS)

Amini, A.; Shenhar, J.; Lum, K.D.

1996-05-01

This report summarizes the phase II work on the Position Location Device (POLO) for penetrometers. Phase II was carried out to generate an integrated design of a full-scale steerable/distance enhanced penetrometer delivery system. Steering provides for the controlled and directional use of the penetrometer, while vibratory thrusting can provide greater penetration ability

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

Science.gov (United States)

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 phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy.

Science.gov (United States)

Mulhall, John P; Burnett, Arthur L; Wang, Run; McVary, Kevin T; Moul, Judd W; Bowden, Charles H; DiDonato, Karen; Shih, Winnie; Day, Wesley W

2013-06-01

We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy. This was a double-blind, placebo controlled, parallel group, phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy. Patients were randomized to 100 or 200 mg avanafil or placebo (taken 30 minutes before sexual activity) for 12 weeks. Primary end points included successful vaginal insertion (Sexual Encounter Profile [SEP] question 2), successful intercourse (SEP3) and change in score on the erectile function domain of the International Index of Erectile Function (IIEF-EF) questionnaire. A total of 298 patients were randomized and 84.6% completed the study. At baseline 16.1% were age 65 years or older and 71.5% had severe erectile dysfunction (mean overall IIEF-EF domain score 9.2). After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo (p erectile function after prostatectomy. Results suggest a rapid onset of action and sustained duration of effect, with all 3 primary end points being achieved at both dose levels. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study.

Science.gov (United States)

O'Donnell, Colin P; Allott, Kelly A; Murphy, Brendan P; Yuen, Hok Pan; Proffitt, Tina-Marie; Papas, Alicia; Moral, Jennifer; Pham, Tee; O'Regan, Michaela K; Phassouliotis, Christina; Simpson, Raelene; McGorry, Patrick D

2016-12-01

Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder. 121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009. Patients taking low-dose antipsychotic medication were randomly assigned to receive once-daily taurine 4 g or placebo for 12 weeks. The coprimary outcomes were change in symptomatology (measured by the Brief Psychiatric Rating Scale [BPRS] total score) and change in cognition (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery composite score) at 12 weeks. Secondary outcomes included tolerability and safety and additional clinical and functioning measures. 86 participants (n = 47 taurine; n = 39 placebo) were included in the final analysis. Taurine significantly improved symptomatology measured by the BPRS total score (95% CI, 1.8-8.5; P = .004) and psychotic subscale (95% CI, 0.1-1.5; P = .026) compared to placebo. Additionally, improvements were observed in the Calgary Depression Scale for Schizophrenia (95% CI, 0.1-3.0; P = .047) and Global Assessment of Functioning (95% CI, 0.3-8.8; P = .04) scores. There was no group difference in composite cognitive score (95% CI, -1.7 to 1.0; P = .582). A significant group difference was found on one safety and tolerability item (psychic item 2, asthenia/lassitude/increased fatigability) of the Udvalg for Kliniske Undersogelser, with the taurine group showing a

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

Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis.

Science.gov (United States)

Murata, Yoko; Song, Michael; Kikuchi, Hisayuki; Hisamichi, Katsuya; Xu, Xie L; Greenspan, Andrew; Kato, Mai; Chiou, Chiun-Fang; Kato, Takeshi; Guzzo, Cynthia; Thurmond, Robin L; Ohtsuki, Mamitaro; Furue, Masutaka

2015-02-01

This trial was conducted to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4 R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect. © 2014 Japanese Dermatological Association.

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...

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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

Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial.

Science.gov (United States)

Janz, David R; Bastarache, Julie A; Rice, Todd W; Bernard, Gordon R; Warren, Melissa A; Wickersham, Nancy; Sills, Gillian; Oates, John A; Roberts, L Jackson; Ware, Lorraine B

2015-03-01

This trial evaluated the efficacy of acetaminophen in reducing oxidative injury, as measured by plasma F2-isoprostanes, in adult patients with severe sepsis and detectable plasma cell-free hemoglobin. Single-center, randomized, double-blind, placebo-controlled phase II trial. Medical ICU in a tertiary, academic medical center. Critically ill patients 18 years old or older with severe sepsis and detectable plasma cell-free hemoglobin. Patients were randomized 1:1 to enteral acetaminophen 1 g every 6 hours for 3 days (n = 18) or placebo (n = 22) with the same dosing schedule and duration. F2-Isoprostanes on study day 3, the primary outcome, did not differ between acetaminophen (30 pg/mL; interquartile range, 24-41) and placebo (36 pg/mL; interquartile range, 25-80; p = 0.35). However, F2-isoprostanes were significantly reduced on study day 2 in the acetaminophen group (24 pg/mL; interquartile range, 19-36) when compared with placebo (36 pg/mL; interquartile range, 23-55; p = 0.047). Creatinine on study day 3, a secondary outcome, was significantly lower in the acetaminophen group (1.0 mg/dL; interquartile range, 0.6-1.4) when compared with that in the placebo (1.3 mg/dL; interquartile range, 0.83-2.0; p = 0.039). There was no statistically significant difference in hospital mortality (acetaminophen 5.6% vs placebo 18.2%; p = 0.355) or adverse events (aspartate aminotransferase or alanine aminotransferase > 400; acetaminophen 9.5% vs placebo 4.3%; p = 0.599). In adults with severe sepsis and detectable plasma cell-free hemoglobin, treatment with acetaminophen within 24 hours of ICU admission may reduce oxidative injury and improve renal function. Additional study is needed to confirm these findings and determine the effect of acetaminophen on patient-centered outcomes.

Design of Phase II Non-inferiority Trials.

Science.gov (United States)

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

Science.gov (United States)

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

Science.gov (United States)

Krege, Susanne; Rexer, Heidrun; vom Dorp, Frank; de Geeter, Patrick; Klotz, Theodor; Retz, Margitte; Heidenreich, Axel; Kühn, Michael; Kamradt, Joern; Feyerabend, Susan; Wülfing, Christian; Zastrow, Stefan; Albers, Peter; Hakenberg, Oliver; Roigas, Jan; Fenner, Martin; Heinzer, Hans; Schrader, Mark

2014-03-01

To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine-kinase inhibitor, compared with chemotherapy alone as first-line treatment in advanced urothelial cancer. The study was a randomized phase II trial. Its primary aim was to show an improvement in progression-free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double-blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3-21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand-foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS. © 2013 The Authors

Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis.

Science.gov (United States)

de Carvalho, Mamede; Pinto, Susana; Costa, João; Evangelista, Teresinha; Ohana, Bemjamim; Pinto, Anabela

2010-10-01

Our objective is to describe the results of a phase II/III, 12-months, double-blinded, single-centre, randomized, parallel (1:1), clinical trial performed to evaluate the efficacy and safety of memantine in ALS. Patients with probable or definite ALS of less than 36 months disease duration and progression over a one-month lead-in period were randomly assigned to placebo or memantine at 20 mg/day. The primary endpoint was 12-months ALSFRS decline. Forced vital capacity, manual muscle testing, visual analogue scale, quality of life, motor unit number estimation and neurophysiological index were the secondary endpoints. The number of patients included was based on the assumption of a 50% change in the ALSFRS decline. Safety and adverse events were evaluated. Sixty-three patients were included in the trial. Memantine did not show more adverse events or laboratory changes than placebo. Primary and secondary outcomes were not different between groups by intention-to-treat and per-protocol analysis. The most sensitive measurements were neurophysiological, which declined linearly over time. In conclusion, the results of this study show that memantine is well tolerated and safe in ALS patients. We did not observe any evidence of efficacy for memantine but we cannot exclude a positive outcome on survival.

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...

N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

International Nuclear Information System (INIS)

Miller, Robert C.; Petereit, Daniel G.; Sloan, Jeff A.; Liu, Heshan; Martenson, James A.; Bearden, James D.; Sapiente, Ronald; Seeger, Grant R.; Mowat, Rex B.; Liem, Ben; Iott, Matthew J.; Loprinzi, Charles L.

2016-01-01

Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.

N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Miller, Robert C., E-mail: miller.robert@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Petereit, Daniel G. [Rapid City Regional Oncology Group, Rapid City, South Dakota (United States); Sloan, Jeff A.; Liu, Heshan [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Martenson, James A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Bearden, James D. [Upstate Carolina Community Clinical Oncology Program, Spartanburg, South Carolina (United States); Sapiente, Ronald [Carle Cancer Center CCOP, Urbana, Illinois (United States); Seeger, Grant R. [Altru Health Systems, Grand Forks, North Dakota (United States); Mowat, Rex B. [Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio (United States); Liem, Ben [University of New Mexico, Albuquerque, New Mexico (United States); Iott, Matthew J. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Loprinzi, Charles L. [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States)

2016-07-15

Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.

PISA. The effect of paracetamol (acetaminophen and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690

Directory of Open Access Journals (Sweden)

Kappelle Jaap

2002-03-01

Full Text Available Abstract Background During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily and low dose (3 g daily paracetamol (acetaminophen in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. Aim The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. Design Seventy-five (3 × 25 patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Micka, Antje; Siepelmeyer, Anne; Holz, Anja; Theis, Stephan; Schön, Christiane

2017-02-01

Constipation is among the most common health impairments in Western countries. This study aimed to determine the effect of the chicory-derived fermentable dietary fiber Orafti ® Inulin on stool frequency in healthy subjects with constipation. The study was conducted according to recent guidance documents for investigating bowel function and used a randomized, double-blind, placebo-controlled, cross-over design with a 2-week wash-out phase. Each study period comprised a run-in phase followed by 4 weeks daily intake of 3 × 4g inulin or maltodextrin (placebo). Forty-four healthy volunteers with constipation documented stool frequency and consistency, gastrointestinal characteristics and quality of life. Consumption of Orafti ® Inulin significantly increased stool frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0] stools/week, p = 0.038). This was accompanied by a softening of stools and trend toward higher satisfaction versus placebo (p = 0.059). In conclusion, Orafti ® Inulin was effective in volunteers with chronic constipation and significantly improved bowel function. This trial was registered at clinicaltrials.gov as NCT02548247.

Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study.

Science.gov (United States)

Kapil, Vikas; Khambata, Rayomand S; Robertson, Amy; Caulfield, Mark J; Ahluwalia, Amrita

2015-02-01

Single dose administration of dietary inorganic nitrate acutely reduces blood pressure (BP) in normotensive healthy volunteers, via bioconversion to the vasodilator nitric oxide. We assessed whether dietary nitrate might provide sustained BP lowering in patients with hypertension. We randomly assigned 68 patients with hypertension in a double-blind, placebo-controlled clinical trial to receive daily dietary supplementation for 4 weeks with either dietary nitrate (250 mL daily, as beetroot juice) or a placebo (250 mL daily, as nitrate-free beetroot juice) after a 2-week run-in period and followed by a 2-week washout. We performed stratified randomization of drug-naive (n=34) and treated (n=34) patients with hypertension aged 18 to 85 years. The primary end point was change in clinic, ambulatory, and home BP compared with placebo. Daily supplementation with dietary nitrate was associated with reduction in BP measured by 3 different methods. Mean (95% confidence interval) reduction in clinic BP was 7.7/2.4 mm Hg (3.6-11.8/0.0-4.9, Pnitrate consumption with no change after placebo. The intervention was well tolerated. This is the first evidence of durable BP reduction with dietary nitrate supplementation in a relevant patient group. These findings suggest a role for dietary nitrate as an affordable, readily-available, adjunctive treatment in the management of patients with hypertension (funded by The British Heart Foundation). http://www.clinicaltrials.gov. Unique identifier: NCT01405898. © 2014 American Heart Association, Inc.

Vitamin E in aging persons with Down syndrome: A randomized, placebo-controlled clinical trial.

Science.gov (United States)

Sano, Mary; Aisen, Paul S; Andrews, Howard F; Tsai, Wei-Yann; Lai, Florence; Dalton, Arthur J

2016-05-31

To determine whether vitamin E would slow the progression of cognitive deterioration and dementia in aging persons with Down syndrome (DS). A randomized, double-blind controlled clinical trial was conducted at 21 clinical sites, and researchers trained in research procedures recruited adults with DS older than 50 years to participate. Participants were randomly assigned to receive 1,000 IU of vitamin E orally twice daily for 3 years or identical placebo. The primary outcome was change on the Brief Praxis Test (BPT). Secondary outcomes included incident dementia and measures of clinical global change, cognition, function, and behavior. A total of 337 individuals were randomized, 168 to vitamin E and 169 to placebo. Both groups demonstrated deterioration on the BPT with no difference between drug and placebo. At baseline, 26% were diagnosed with dementia and there was an overall rate of incident dementia of 11%/year with no difference between groups. There was no effect on the secondary outcome measures. Though numerically higher in the treatment group, there was no difference in the number of adverse events (p = 0.079) and deaths (p = 0.086) between groups. Vitamin E did not slow the progression of cognitive deterioration in older individuals with DS. This study provides Class II evidence that vitamin E does not significantly slow the progression of cognitive deterioration in aging persons with DS. © 2016 American Academy of Neurology.

A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.

Science.gov (United States)

Toniolo, Ricardo Alexandre; Silva, Michelle; Fernandes, Francy de Brito Ferreira; Amaral, José Antonio de Mello Siqueira; Dias, Rodrigo da Silva; Lafer, Beny

2018-02-01

Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression. We conducted a double-blind trial in which 35 patients with bipolar disorder type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17) or placebo (N = 18). Primary efficacy was assessed by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS). We did not find a statistically significant difference in the comparison between groups for the change in score on the MADRS after 6 weeks in an intention-to-treat (ITT) analysis (p = 0.560; Cohen's d = 0.231). However, we found significant superiority of creatine add-on vs. placebo when we considered the remission criterion of a MADRS score ≤ 12 at week 6 analyzing the outcome of the 35 randomized patients on ITT (52.9% remission in the creatine group vs. 11.1% remission in the placebo group) and of the 23 completers (66.7% remission in the creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched to hypomania/mania early in the trial. No clinically relevant physical side-effects were reported or observed. This proof-of-concept study, aiming to restore brain bioenergetics using an adjunctive mitochondrial modulator, is not conclusive on the efficacy of creatine add-on for bipolar

Randomized, Placebo-Controlled Phase 2 Trial of a Lactobacillus crispatus Probiotic Given Intravaginally for Prevention of Recurrent Urinary Tract Infection

OpenAIRE

Stapleton, Ann E.; Au-Yeung, Melissa; Hooton, Thomas M.; Fredricks, David N.; Roberts, Pacita L.; Czaja, Christopher A.; Yarova-Yarovaya, Yuliya; Fiedler, Tina; Cox, Marsha; Stamm, Walter E.

2011-01-01

In a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (LACTIN-VÜ, Osel, Inc.) for prevention of recurrent UTI (rUTI) in pre-menopausal women, LACTIN-V was safe, well tolerated, and associated with a reduction in rUTI.

Centrifuge workers study. Phase II, completion report

International Nuclear Information System (INIS)

Wooten, H.D.

1994-09-01

Phase II of the Centrifuge Workers Study was a follow-up to the Phase I efforts. The Phase I results had indicated a higher risk than expected among centrifuge workers for developing bladder cancer when compared with the risk in the general population for developing this same type of cancer. However, no specific agent could be identified as the causative agent for these bladder cancers. As the Phase II Report states, Phase I had been limited to workers who had the greatest potential for exposure to substances used in the centrifuge process. Phase II was designed to expand the survey to evaluate the health of all employees who had ever worked in Centrifuge Program Departments 1330-1339 but who had not been interviewed in Phase I. Employees in analytical laboratories and maintenance departments who provided support services for the Centrifuge Program were also included in Phase II. In December 1989, the Oak Ridge Associated Universities (ORAU), now known as Oak Ridge Institute for Science and Education (ORISE), was contracted to conduct a follow-up study (Phase II). Phase H of the Centrifuge Workers Study expanded the survey to include all former centrifuge workers who were not included in Phase I. ORISE was chosen because they had performed the Phase I tasks and summarized the corresponding survey data therefrom

Centrifuge workers study. Phase II, completion report

Energy Technology Data Exchange (ETDEWEB)

Wooten, H.D.

1994-09-01

Phase II of the Centrifuge Workers Study was a follow-up to the Phase I efforts. The Phase I results had indicated a higher risk than expected among centrifuge workers for developing bladder cancer when compared with the risk in the general population for developing this same type of cancer. However, no specific agent could be identified as the causative agent for these bladder cancers. As the Phase II Report states, Phase I had been limited to workers who had the greatest potential for exposure to substances used in the centrifuge process. Phase II was designed to expand the survey to evaluate the health of all employees who had ever worked in Centrifuge Program Departments 1330-1339 but who had not been interviewed in Phase I. Employees in analytical laboratories and maintenance departments who provided support services for the Centrifuge Program were also included in Phase II. In December 1989, the Oak Ridge Associated Universities (ORAU), now known as Oak Ridge Institute for Science and Education (ORISE), was contracted to conduct a follow-up study (Phase II). Phase H of the Centrifuge Workers Study expanded the survey to include all former centrifuge workers who were not included in Phase I. ORISE was chosen because they had performed the Phase I tasks and summarized the corresponding survey data therefrom.

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 ...

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.

Sample Exchange Evaluation (SEE) Report - Phase II

Energy Technology Data Exchange (ETDEWEB)

Winters, W.I.

1994-09-28

This report describes the results from Phase II of the Sample Exchange Evaluation (SEE) Program, a joint effort to compare analytical laboratory performance on samples from the Hanford Site`s high-level waste tanks. In Phase II, the program has been expanded to include inorganic constituents in addition to radionuclides. Results from Phase II that exceeded 20% relative percent difference criteria are identified.

Sample Exchange Evaluation (SEE) Report - Phase II

International Nuclear Information System (INIS)

Winters, W.I.

1994-01-01

This report describes the results from Phase II of the Sample Exchange Evaluation (SEE) Program, a joint effort to compare analytical laboratory performance on samples from the Hanford Site's high-level waste tanks. In Phase II, the program has been expanded to include inorganic constituents in addition to radionuclides. Results from Phase II that exceeded 20% relative percent difference criteria are identified

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...

A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

Directory of Open Access Journals (Sweden)

Jozef Vojtaššák

2011-01-01

Full Text Available Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA. Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

Science.gov (United States)

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

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

Science.gov (United States)

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.

Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.

Science.gov (United States)

Stracke, H; Gaus, W; Achenbach, U; Federlin, K; Bretzel, R G

2008-11-01

Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial

Science.gov (United States)

Haas, Naomi B; Manola, Judith; Uzzo, Robert G; Flaherty, Keith T; Wood, Christopher G; Kane, Christopher; Jewett, Michael; Dutcher, Janice P; Atkins, Michael B; Pins, Michael; Wilding, George; Cella, David; Wagner, Lynne; Matin, Surena; Kuzel, Timothy M; Sexton, Wade J; Wong, Yu-Ning; Choueiri, Toni K; Pili, Roberto; Puzanov, Igor; Kohli, Manish; Stadler, Walter; Carducci, Michael; Coomes, Robert; DiPaola, Robert S

2016-01-01

Summary Background Renal-cell carcinoma is highly vascular, and proliferates primarily through dysregulation of the vascular endothelial growth factor (VEGF) pathway. We tested sunitinib and sorafenib, two oral anti-angiogenic agents that are effective in advanced renal-cell carcinoma, in patients with resected local disease at high risk for recurrence. Methods In this double-blind, placebo-controlled, randomised, phase 3 trial, we enrolled patients at 226 study centres in the USA and Canada. Eligible patients had pathological stage high-grade T1b or greater with completely resected non-metastatic renal-cell carcinoma and adequate cardiac, renal, and hepatic function. Patients were stratified by recurrence risk, histology, Eastern Cooperative Oncology Group (ECOG) performance status, and surgical approach, and computerised double-blind randomisation was done centrally with permuted blocks. Patients were randomly assigned (1:1:1) to receive 54 weeks of sunitinib 50 mg per day orally throughout the first 4 weeks of each 6 week cycle, sorafenib 400 mg twice per day orally throughout each cycle, or placebo. Placebo could be sunitinib placebo given continuously for 4 weeks of every 6 week cycle or sorafenib placebo given twice per day throughout the study. The primary objective was to compare disease-free survival between each experimental group and placebo in the intention-to-treat population. All treated patients with at least one follow-up assessment were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00326898. Findings Between April 24, 2006, and Sept 1, 2010, 1943 patients from the National Clinical Trials Network were randomly assigned to sunitinib (n=647), sorafenib (n=649), or placebo (n=647). Following high rates of toxicity-related discontinuation after 1323 patients had enrolled (treatment discontinued by 193 [44%] of 438 patients on sunitinib, 199 [45%] of 441 patients on sorafenib), the starting dose of each

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

Directory of Open Access Journals (Sweden)

Nativ Ofer

2012-11-01

Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial.

Science.gov (United States)

Cornu, Catherine; Remontet, Laurent; Noel-Baron, Florence; Nicolas, Alain; Feugier-Favier, Nathalie; Roy, Pascal; Claustrat, Bruno; Saadatian-Elahi, Mitra; Kassaï, Behrouz

2010-06-22

To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders. Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group) or olive oil (placebo group) for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i) perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii) sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii) night melatonin and 6 sulfatoxymelatonin (aMT6S) urine rates in a subsample of subjects. The average of Leeds score was similar in both groups (p = 0.95). A marked improvement in the quality of sleep was observed in both placebo (62%) and active (65%) group (p = 0.52). The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91). The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. clinical trials.gov:NCT00484497.

A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy.

Science.gov (United States)

Goemans, Nathalie; Mercuri, Eugenio; Belousova, Elena; Komaki, Hirofumi; Dubrovsky, Alberto; McDonald, Craig M; Kraus, John E; Lourbakos, Afrodite; Lin, Zhengning; Campion, Giles; Wang, Susanne X; Campbell, Craig

2018-01-01

This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings. Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity. The increased standard deviation alone, due to less stringent inclusion/exclusion criteria, reduced the statistical power from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300-400 meters and ability to rise from floor. A statistically significant improvement in 6MWD of 35.4 meters (P = 0.039) in favor of drisapersen was observed in this subpopulation. Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Military Family Coping Project - Phase II

Science.gov (United States)

2015-05-01

Anxiety, Life Satisfaction , Addiction, Trauma 4 The Military Family Coping Project reflects two phases. The first consisted of a series of focus...need for and guided the work of the Military Family Coping Project Phase II funded by TATRC. The Military Family Coping Project Phase II was...solidarity. For the purposes of family functioning analyses, married and unmarried soldiers were analyzed separately because marital status affects

Phase II clinical development of new drugs

CERN Document Server

Ting, Naitee; Ho, Shuyen; Cappelleri, Joseph C

2017-01-01

This book focuses on how to appropriately plan and develop a Phase II program, and how to design Phase II clinical trials and analyze their data. It provides a comprehensive overview of the entire drug development process and highlights key questions that need to be addressed for the successful execution of Phase II, so as to increase its success in Phase III and for drug approval. Lastly it warns project team members of the common potential pitfalls and offers tips on how to avoid them.

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

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Bruix, Jordi; Qin, Shukui; Merle, Philippe; Granito, Alessandro; Huang, Yi-Hsiang; Bodoky, György; Pracht, Marc; Yokosuka, Osamu; Rosmorduc, Olivier; Breder, Valeriy; Gerolami, René; Masi, Gianluca; Ross, Paul J; Song, Tianqiang; Bronowicki, Jean-Pierre; Ollivier-Hourmand, Isabelle; Kudo, Masatoshi; Cheng, Ann-Lii; Llovet, Josep M; Finn, Richard S; LeBerre, Marie-Aude; Baumhauer, Annette; Meinhardt, Gerold; Han, Guohong

2017-01-07

There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344. Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50-0·79; one-sided p<0·0001); median survival was 10·6 months (95% CI 9·1-12·1) for regorafenib versus 7·8 months (6·3-8·8) for placebo. Adverse events were reported in all regorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinically relevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group

A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.

Science.gov (United States)

Jung, Chang Hee; Park, Cheol-Young; Ahn, Kyu-Joeng; Kim, Nan-Hee; Jang, Hak-Chul; Lee, Moon-Kyu; Park, Joong-Yeol; Chung, Choon-Hee; Min, Kyung-Wan; Sung, Yeon-Ah; Park, Jeong-Hyun; Kim, Sung Jin; Lee, Hyo Jung; Park, Sung-Woo

2015-03-01

DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2) ). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

Aerospace Systems Monitor, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Proposal Title: Aerospace Systems Monitor PHASE 1 Technical Abstract: This Phase II STTR project will continue development and commercialization of the Aerospace...

Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Fleischhacker, W Wolfgang; Heikkinen, Martti E; Olié, Jean-Pierre; Landsberg, Wally; Dewaele, Patricia; McQuade, Robert D; Loze, Jean-Yves; Hennicken, Delphine; Kerselaers, Wendy

2010-09-01

Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, pweight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

Adaptive nonlinear control of single-phase to three-phase UPS system

Directory of Open Access Journals (Sweden)

Kissaoui M.

2014-01-01

Full Text Available This work deals with the problems of uninterruptible power supplies (UPS based on the single-phase to three-phase converters built in two stages: an input bridge rectifier and an output three phase inverter. The two blocks are joined by a continuous intermediate bus. The objective of control is threefold: i power factor correction “PFC”, ii generating a symmetrical three-phase system at the output even if the load is unknown, iii regulating the DC bus voltage. The synthesis of controllers has been reached by two nonlinear techniques that are the sliding mode and adaptive backstepping control. The performances of regulators have been validated by numerical simulation in MATLAB / SIMULINK.

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

Science.gov (United States)

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.

Burn-up Credit Criticality Safety Benchmark-Phase II-E. Impact of Isotopic Inventory Changes due to Control Rod Insertions on Reactivity and the End Effect in PWR UO2 Fuel Assemblies

International Nuclear Information System (INIS)

Neuber, Jens Christian; Tippl, Wolfgang; Hemptinne, Gwendoline de; Maes, Philippe; Ranta-aho, Anssu; Peneliau, Yannick; Jutier, Ludyvine; Tardy, Marcel; Reiche, Ingo; Kroeger, Helge; Nakata, Tetsuo; Armishaw, Malcom; Miller, Thomas M.

2015-01-01

The report describes the final results of the Phase II-E Burn-up Credit Criticality Benchmark conducted by the Expert Group on Burn-up Credit Criticality Safety. The objective of Phase II of the Burn-up Credit Criticality Safety programme is to study the impact of axial burn-up profiles of PWR UO 2 spent fuel assemblies on the reactivity of PWR UO 2 spent fuel assembly configurations. The objective of the Phase II-E benchmark was to study the impact of changes on the spent nuclear fuel isotopic composition due to control rod insertion during depletion on the reactivity and the end effect of spent fuel assemblies with realistic axial burn-up profiles for different control rod insertion depths ranging from 0 cm (no insertion) to full insertion (i.e. to the case that the fuel assemblies were exposed to control rod insertion over their full active length). For this purpose two axial burn-up profiles have been extracted from an AREVA-NP-GmbH-owned 17x17-(24+1) PWR UO 2 spent fuel assembly burn-up profile database. One profile has an average burn-up of 30 MWd/kg U, the other profile is related to an average burn-up of 50 MWd/kg U. Two profiles with different average burn-up values were selected because the shape of the burn-up profile is affected by the average burn-up and the end effect depends on the average burn-up of the fuel. The Phase II-E benchmark exercise complements the Phase II-C and Phase II-D benchmark exercises. In Phase II-D different irradiation histories were analysed using different control rod insertion histories during depletion as well as irradiation histories without control rod insertion. But in all the histories analysed a uniform distribution of the burn-up and hence a uniform distribution of the isotopic composition were assumed; and in all the histories including any usage of control rods full insertion of the control rods was assumed. In Phase II-C the impact of the asymmetry of axial burn-up profiles on the reactivity and the end effect of

Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study.

Science.gov (United States)

Singh, Arvinderpal; Sharma, Geeta; Gupta, Ruchi; Kumari, Anita; Tikko, Deepika

2016-01-01

Pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia. Tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice. However, their potential to relieve propofol injection pain still needs to be explored. A randomized, double-blind, placebo-controlled study was conducted on 90 American Society of Anesthesiologists I and II adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent. Consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each. Group I patients received an injection of normal saline 3 ml intravenously (placebo) while Group II and Group III patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously, respectively. Before induction of anesthesia patients were asked about the intensity of pain on propofol injection by using visual analog scale (VAS) before the loss of consciousness. Descriptive statistics and analysis of variance with Chi-square test were used to analyze the data. The value of P pain in Group I was observed in 80% of the patients, while it was observed in 23.33% and 20% of patients in Group II and III, respectively. Mean VAS scores were 2.27 ± 1.51, 1.14 ± 1.74, and 1.03 ± 1.72 in Group I, II, and Group III patients, respectively. The incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in Group II and III, respectively. Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain.

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.

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.

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

Science.gov (United States)

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

Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study.

Science.gov (United States)

Jacobs, Teresa L; Brown, Devin L; Baek, Jonggyu; Migda, Erin M; Funckes, Timothy; Gruis, Kirsten L

2016-11-01

To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) NIV for clinical symptom management. In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar. © 2016 American Academy of Neurology.

Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection.

Science.gov (United States)

Stapleton, Ann E; Au-Yeung, Melissa; Hooton, Thomas M; Fredricks, David N; Roberts, Pacita L; Czaja, Christopher A; Yarova-Yarovaya, Yuliya; Fiedler, Tina; Cox, Marsha; Stamm, Walter E

2011-05-01

Urinary tract infections (UTIs) are common among women and frequently recur. Depletion of vaginal lactobacilli is associated with UTI risk, which suggests that repletion may be beneficial. We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) for prevention of recurrent UTI in premenopausal women. One hundred young women with a history of recurrent UTI received antimicrobials for acute UTI and then were randomized to receive either Lactin-V or placebo daily for 5 d, then once weekly for 10 weeks. Participants were followed up at 1 week and 10 weeks after intervention and for UTIs; urine samples for culture and vaginal swabs for real-time quantitative 16S ribosomal RNA gene polymerase chain reaction for L. crispatus were collected. Recurrent UTI occurred in 7/48 15% of women receiving Lactin-V compared with 13/48 27% of women receiving placebo (relative risk [RR], .5; 95% confidence interval, .2-1.2). High-level vaginal colonization with L. crispatus (≥10(6) 16S RNA gene copies per swab) throughout follow-up was associated with a significant reduction in recurrent UTI only for Lactin-V (RR for Lactin-V, .07; RR for placebo, 1.1; P < .01). Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI. Larger efficacy trials of this novel preventive method for recurrent UTI are warranted. CLINICAL TRIALS REGISTRATION. NCT00305227.

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial.

Science.gov (United States)

Jeong, Jae Yoon; Sohn, Joo Hyun; Baek, Yang Hyun; Cho, Yong Kyun; Kim, Yongsoo; Kim, Hyeonjin

2017-08-28

To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease (NAFLD). Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose (400 mg) HL tablet, low dose (133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content (HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index (BMI). The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment (high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were -1.7% ± 3.1% in the high dose group ( P = 0.018), -1.21% ± 4.97% in the low dose group ( P = 0.254) and 0.61% ± 3.87% in the placebo group (relative changes compared to baseline, high dose were: -12.1% ± 23.5%, low dose: -3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study. HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

Results of a non-specific immunomodulation therapy on chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial

DEFF Research Database (Denmark)

Torre-Amione, G.; Anker, S.D.; Bourge, R.C.

2008-01-01

Background Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. Methods We did a double-blind, placebo-controlled s......Background Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. Methods We did a double-blind, placebo......-controlled study of a device-based non-specific immunomodulation therapy (IMT) in patients with New York Heart Association (NYHA) functional class II-IV chronic heart failure, left ventricular (LV) systolic dysfunction, and hospitalisation for heart failure or intravenous drug therapy in an outpatient setting......-0 . 95; p=0.02) and a 39% (0.61; 95% CI 0 . 46-0.80; p=0 . 0003) reduction in the risk of primary endpoint events, respectively. Interpretation Non-specific immunomodulation may have a role as a potential treatment for a large segment of the heart failure population, which includes patients without...

A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

DEFF Research Database (Denmark)

Orwoll, Eric; Teglbjærg, Christence S; Langdahl, Bente Lomholt

2012-01-01

Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study...... by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations....... Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P adverse events was similar between groups. Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases...

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

Directory of Open Access Journals (Sweden)

Claustrat Bruno

2010-06-01

Full Text Available Abstract Background To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ in subjects with moderate to severe sleep disorders. Methods Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group or olive oil (placebo group for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii night melatonin and 6 sulfatoxymelatonin (aMT6S urine rates in a subsample of subjects. Results The average of Leeds score was similar in both groups (p = 0.95. A marked improvement in the quality of sleep was observed in both placebo (62% and active (65% group (p = 0.52. The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91. Conclusions The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. Trial registration: clinical trials.gov:NCT00484497

Effects of fixed orthodontic treatment and two new mouth rinses on gingival health: A prospective cohort followed by a single-blind placebo-controlled randomized clinical trial.

Science.gov (United States)

Sobouti, Farhad; Rakhshan, Vahid; Heydari, Mohaddeseh; Keikavusi, Shohreh; Dadgar, Sepideh; Shariati, Mahsa

2018-03-01

Routine brushing protocols might not suffice to reduce the increased plaque accumulation in orthodontic patients. Antimicrobial mouth rinses are favorable in this regard. This two-phase study evaluated the effects of orthodontic treatment and the application of two mouthwashes not studied before on oral health indices. In this two-phase study (a prospective cohort followed by a parallel randomized controlled trial), plaque index (PI), gingival index (GI), gingival bleeding index (GBI), and pocket probing depth (PPD) were measured in 54 orthodontic patients before orthodontic treatment and 4 months later. Then patients were randomized into three groups of mouthrinses: Persica (herbal), Ortho-Kin (containing diluted chlorhexidine), and Placebo (n=18×3). The effects of orthodontic treatment and mouthrinses were analyzed statistically (α=0.05). All the 4 indices increased between the baseline and 4th month of treatment (P values<0.01, paired t-test). They decreased back to baseline levels or below them, after one month of mouthwash application (P values<0.002). Both mouthwashes showed therapeutic effects compared to placebo in terms of PI and GBI. In the case of GI, only Persica showed significantly better results compared to placebo. Regarding PPD, only Ortho-Kin acted better than placebo (P values≤0.05, Tukey). Lack of positive control (regular chlorhexidine mouth rinse) and negative control (a group with no mouthwashes, even without the placebo). Lack of sample size predetermination based on a priori power calculations. The difference between the regime of Persica with that of Ortho-Kin and placebo (which had similar application protocols) disallowed perfectly effective blinding of the patients (hence, single-blind). Fixed orthodontic treatment might disrupt gingival health. Antimicrobial mouthwashes might reverse this. Both evaluated mouthwashes might have therapeutic effects. Copyright © 2018 CEO. Published by Elsevier Masson SAS. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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. 

First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy.

Directory of Open Access Journals (Sweden)

Peter A Anton

Full Text Available Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.HIV-1 seronegative, sexually-abstinent men and women (N = 36 were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25% with placebo gel (1∶1∶1. Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.All 36 subjects enrolled completed the 7-14 week trial (100% retention including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm. There were 81 Grade 1 adverse events (AEs and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1(BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV

Double-blind, placebo-controlled pilot study of adjunctive quetiapine SR in the treatment of PMS/PMDD.

Science.gov (United States)

Jackson, Christine; Pearson, Brenda; Girdler, Susan; Johnson, Jacqueline; Hamer, Robert M; Killenberg, Susan; Meltzer-Brody, Samantha

2015-11-01

Premenstrual dysphoric disorder (PMDD), a more severe form of premenstrual syndrome (PMS), afflicts 5-8% of reproductive age women and results in significant functional impairment. We conducted a double-blind, placebo-controlled trial of adjunctive quetiapine in patients with PMS/PMDD who had inadequate response to selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy for their symptoms. A PMS/PMDD diagnosis was confirmed by 2-month prospective diagnostic assessment of PMS/PMDD using the Prospective Record of the Impact and Severity of Premenstrual Symptoms (PRISM) calendar. Women were randomized equally to receive quetiapine sustained-release (SR) or placebo (25-mg starting dose) during the luteal phase for 3 months. Outcome variables included the Hamilton Depression and Anxiety Scales, Clinical Global Impression Scale, and PRISM. Twenty women were enrolled in the treatment phase. Although the study was underpowered, greater reductions in luteal phase mood ratings were observed in the quetiapine group on the 17-item Hamilton Depression Rating Scale, Clinical Global Impression improvement rating, and PRISM daily score. The quetiapine group showed most improvement in symptoms of mood lability, anxiety, and irritability. This small double-blind study suggests that adjunctive treatment with quetiapine SR may be a useful addition to selective serotonin reuptake inhibitor therapy in women with PMS/PMDD by reducing symptoms and improving quality of life. Copyright © 2015 John Wiley & Sons, Ltd.

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.

Re: A Randomized Double-Blind Placebo-Controlled Phase 2 Dose-Ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

Directory of Open Access Journals (Sweden)

Ozan Bozkurt

2015-09-01

Full Text Available Botulinum toxin is a neurotoxin inhibiting the release of acetylcholine and is used in various fields of medicine. Recently, it has been proposed as an alternative minimally invasive treatment modality for patients unresponsive to oral therapies. The present study is the largest prospective, randomized and placebo-controlled study investigating the efficacy and safety of different onabotulinumtoxinA (BTX-A doses in men with moderate to severe lower urinary tract symptoms (LUTS associated with benign prostatic hyperplasia (BPH. 100 U, 200 U and 300 U BTX-A doses via transperineal or transrectal route were injected within the transition zone of each lateral lobe. 69.7% of patients (115 of 380 completed the 72-week study. The authors reported significant improvement for all treatment arms including placebo from weeks 2 through 72 including the primary time point of week 12. There were no statistically significant differences between BTX-A groups and placebo in terms of treatment efficacy described as International Prostate Symptom Score (IPSS reduction, improvement of peak urinary flow rate (Qmax and post-void residual volume (PVR and prostate volume reduction at any time point throughout the study. Only in a subgroup of patients, including previous alpha-blocker users, 200 U BTX-A worked better than placebo in terms of IPSS reduction. Adverse event rates were similar between all treatment arms. The unexpected pronounced placebo response in the present study raises question marks in minds regarding the use of BTX-A as an alternative treatment option. These conflicting results suggest that intraprostatic BTX-A injection is still experimental and further trials are required.

Status of Gerda Phase II

Energy Technology Data Exchange (ETDEWEB)

Wagner, Victoria [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Collaboration: GERDA-Collaboration

2016-07-01

The GERDA experiment is designed to search for neutrinoless double beta (0νββ) decay of {sup 76}Ge. In Phase I of the experiment a background index (BI) of 10{sup -2} cts/(keV.kg.yr) was reached. No signal has been found and a lower limit on the half-life of 2.1.10{sup 25} yr (at 90% C.L.) is extracted. The aim of Phase II is to double the Ge mass and further reduce the BI by an order of magnitude to explore half-lives of about 10{sup 26} yr. Thirty new Broad Energy Germanium (BEGe) detectors have been produced. These detectors are distinct for their improved energy resolution and enhanced pulse shape discrimination of signal from background events. Further background reduction will be reached by an active veto to read out argon scintillation light. The Phase II commissioning showed that two of the major background components, external γ-rays from {sup 214}Bi and {sup 208}Tl decays, can be suppressed up to two orders of magnitude. This talk presents the current status of the GERDA Phase II upgrade.

Rasagiline for mild cognitive impairment in Parkinson's disease: A placebo-controlled trial.

Science.gov (United States)

Weintraub, Daniel; Hauser, Robert A; Elm, Jordan J; Pagan, Fernando; Davis, Matthew D; Choudhry, Azhar

2016-05-01

This study's aims were to determine the efficacy and tolerability of rasagiline, a selective monoamine oxidase inhibitor B, for PD patients with mild cognitive impairment. Patients on stable dopaminergic therapy were randomized to adjunct rasagiline 1 mg/day or placebo in this 24-week, double-blind, placebo-controlled, multisite study. The primary endpoint was mean change from baseline to week 24 on the Scales for Outcomes of Parkinson's Disease-Cognition total score. Key secondary measures included changes in cognition, activities of daily living, motor scores, and Clinical Global Impression of Change, as well as safety and tolerability measures. Of the 170 patients randomized, 151 (88.2%) completed the study. Change in Scales for Outcomes of Parkinson's Disease-Cognition scores were not significantly different in the rasagiline and placebo groups (adjusted mean: 1.6 [standard error {SE} = 0.5] vs. 0.8 [SE = 0.5] points; LS means difference = 0.8; 95% confidence interval: -0.48, 2.05; P = 0.22). There were no between-group differences in change in the MoCA (p=0.84) or Penn Daily Activities Questionnaire (P = 0.48) scores or in the distribution of Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change modified for mild cognitive impairment (P = 0.1). Changes in motor (UPDRS part III; P = 0.02) and activities of daily living (UPDRS part II; P rasagiline. Rasagiline was well tolerated; the most common adverse events in both groups were falls and dizziness. Rasagiline treatment in PD patients with mild cognitive impairment was not associated with cognitive improvement. Rasagiline did not worsen cognition, improved motor symptoms and activities of daily living, and was well tolerated in elderly cognitively impaired patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Nations, Kari R; Dogterom, Peter; Bursi, Roberta; Schipper, Jacques; Greenwald, Scott; Zraket, David; Gertsik, Lev; Johnstone, Jack; Lee, Allen; Pande, Yogesh; Ruigt, Ge; Ereshefsky, Larry

2012-12-01

Org 26576 acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. The aim of this Phase 1b study (N=54) was to explore safety, tolerability, pharmacokinetics, and pharmacodynamics of Org 26576 in depressed patients. Part I (N=24) evaluated the maximum tolerated dose (MTD) and optimal titration schedule in a multiple rising dose paradigm (range 100 mg BID to 600 mg BID); Part II (N=30) utilized a parallel groups design (100 mg BID, 400 mg BID, placebo) to examine all endpoints over a 28-day dosing period. Based on the number of moderate intensity adverse events reported at the 600 mg BID dose level, the MTD established in Part I was 450 mg BID. Symptomatic improvement as measured by the Montgomery-Asberg Depression Rating Scale was numerically greater in the Org 26576 groups than in the placebo group in both study parts. In Part II, the 400 mg BID dose was associated with improvements in executive functioning and speed of processing cognitive tests. Org 26576 was also associated with growth hormone increases and cortisol decreases at the end of treatment but did not influence prolactin or brain-derived neurotrophic factor. The quantitative electroencephalogram index Antidepressant Treatment Response at Week 1 was able to significantly predict symptomatic response at endpoint in the active treatment group, as was early improvement in social acuity. Overall, Org 26576 demonstrated good tolerability and pharmacokinetic properties in depressed patients, and pharmacodynamic endpoints suggested that it may show promise in future well-controlled, adequately powered proof of concept trials.

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

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

Science.gov (United States)

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

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

2005-01-01

Objective To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

Directory of Open Access Journals (Sweden)

Hörl Walter H

2010-10-01

Full Text Available Abstract Background New-onset diabetes mellitus after transplantation (NODAT, a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4 inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT. Methods/Design This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l. They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and

Placebo - More hatred than love

Directory of Open Access Journals (Sweden)

Hong-Liang Zhang

2011-01-01

Full Text Available A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs, which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

Placebo - More hatred than love.

Science.gov (United States)

Zhang, Hong-Liang

2011-01-01

A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs), which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

Homeopathy for mental fatigue: lessons from a randomized, triple blind, placebo-controlled cross-over clinical trial

Directory of Open Access Journals (Sweden)

Dean Michael

2012-10-01

Full Text Available Abstract Background Difficulty in controlling attention can lead to mental fatigue in the healthy population. We identified one trial reporting a benefit in patients’ attention using a homeopathic formula preparation. One component of the preparation was potassium phosphate, widely available off the shelf as Kali phos 6x for cognitive problems. The aim of this exploratory trial was to assess the effectiveness of Kali phos 6x for attention problems associated with mental fatigue. Methods We recruited student and staff volunteers (University of York with self-reported mental fatigue, excluding any using homeopathy or prescribed stimulants, or with a diagnosis of chronic fatigue syndrome. In a triple blind, cross-over, placebo-controlled clinical trial, 86 volunteers were randomized to receive Kali phos 6x or identical placebo 10 minutes before taking a psychological test of attention (Stroop Colour-Word Test. One week later they were crossed over and took the other preparation before repeating the test. Results We found no evidence of a treatment effect in a comparison of Kali phos 6x with placebo (Kali phos minus placebo = −1.1 (95% CI −3.0 to 0.9, P = 0.3 Stroop score units, Cohen effect size = −0.17 even when allowing for a weak period effect with accuracy scores in the second period being higher than those in the first (P = 0.05. We observed a ceiling effect in the Stroop test which undermined our ability to interpret this result. Conclusions Kali phos 6x was not found to be effective in reducing mental fatigue. A ceiling effect in our primary outcome measure meant that we could not rule out a type II error. Thorough piloting of an adequate outcome measure could have led to an unequivocal result. Current Controlled Trials ISRCTN16521161

Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naïve patients with chronic pain.

Science.gov (United States)

Arai, Tsutomu; Kashimoto, Yuji; Ukyo, Yoshifumi; Tominaga, Yushin; Imanaka, Keiichiro

2015-12-01

To evaluate the efficacy and safety of fentanyl 1 day patch in opioid-naïve patients with non-cancer chronic pain insufficiently relieved by non-opioid analgesics. Two phase III placebo-controlled, double-blind, group-comparison, randomized withdrawal studies were conducted in patients with osteoarthritis and/or low back pain (N01 study) and post-herpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain (N02) in Japan. Both studies consisted of period I (10-29 days of titration, fentanyl 12.5-50.0 µg/h) and period II (12 weeks double-blind). N01, NCT01008618; N02, NCT01008553 MAIN OUTCOME MEASURES: The primary endpoint was the number of days until study discontinuation due to insufficient pain relief in period II, and secondary endpoints included pain scored on visual analog scale (VAS), subject's overall assessment, the number of rescue dose, brief pain inventory short form score, score on short-form 36-item health survey version 2.0, physician's overall assessment, and assessment of adverse events. Of the 218 (N01) and 258 (N02) subjects who entered period I, 150 and 163 subjects entered period II, respectively. In the N01 study, the between-group difference was significant in the VAS score (95% CI: 7.3 [1.1, 13.5] mm, P = 0.0215) but not in the primary endpoint (P = 0.0846, log-rank test). In the N02 study, both primary efficacy (P = 0.0003) and VAS (8.7 [2.4, 15.0] mm, P = 0.0071) results showed that fentanyl was more effective than placebo. The major adverse events were nervous system and gastrointestinal disorders typically associated with opioid analgesic use. The incidence of adverse events in the fentanyl group was 68.5% to 85.7%. Although the primary efficacy results showed significant effects of fentanyl in the N02 but not the N01 study, overall results showed that fentanyl 1 day patch is effective and well tolerated.

Mercury Oxidation via Catalytic Barrier Filters Phase II

Energy Technology Data Exchange (ETDEWEB)

Wayne Seames; Michael Mann; Darrin Muggli; Jason Hrdlicka; Carol Horabik

2007-09-30

In 2004, the Department of Energy National Energy Technology Laboratory awarded the University of North Dakota a Phase II University Coal Research grant to explore the feasibility of using barrier filters coated with a catalyst to oxidize elemental mercury in coal combustion flue gas streams. Oxidized mercury is substantially easier to remove than elemental mercury. If successful, this technique has the potential to substantially reduce mercury control costs for those installations that already utilize baghouse barrier filters for particulate removal. Completed in 2004, Phase I of this project successfully met its objectives of screening and assessing the possible feasibility of using catalyst coated barrier filters for the oxidation of vapor phase elemental mercury in coal combustion generated flue gas streams. Completed in September 2007, Phase II of this project successfully met its three objectives. First, an effective coating method for a catalytic barrier filter was found. Second, the effects of a simulated flue gas on the catalysts in a bench-scale reactor were determined. Finally, the performance of the best catalyst was assessed using real flue gas generated by a 19 kW research combustor firing each of three separate coal types.

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

Vogt, Liffert; Navis, Gerjan; Köster, Jürgen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

2005-01-01

To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. The

Plasma Control of Turbine Secondary Flows, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — We propose Phase I and II efforts that will focus on turbomachinery flow control. Specifically, the present work will investigate active control in a high speed...

Lactobacillus reuteri strain combination in Helicobacter pylori infection: a randomized, double-blind, placebo-controlled study.

Science.gov (United States)

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.

Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Weintraub, Michael I; Wolfe, Gil I; Barohn, Richard A; Cole, Steven P; Parry, Gareth J; Hayat, Ghazala; Cohen, Jeffrey A; Page, Jeffrey C; Bromberg, Mark B; Schwartz, Sherwyn L

2003-05-01

To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN). Randomized, placebo-control, parallel study. Forty-eight centers in 27 states. Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device. Nerve conduction and/or quantified sensory testing were performed serially. Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (ANCOVA), and chi-square analysis were performed. There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, -12%; for sham, -3%; P<.05, ANCOVA), numbness and tingling (magnet, -10%; sham, +1%; P<.05, ANCOVA), and exercise-induced foot pain (magnet, -12%; sham, -4%; P<.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, -32%; sham, -14%; P<.01, ANOVA) and foot pain (magnet, -41%; sham, -21%; P<.01, ANOVA). Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

Science.gov (United States)

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

Science.gov (United States)

Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

2013-11-01

Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial.

Science.gov (United States)

Winthrop, Kevin L; Wouters, Ann G; Choy, Ernest H; Soma, Koshika; Hodge, Jennifer A; Nduaka, Chudy I; Biswas, Pinaki; Needle, Elie; Passador, Sherry; Mojcik, Christopher F; Rigby, William F

2017-10-01

Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster, and vaccination is recommended for patients ages 50 years and older, prior to starting treatment with biologic agents or tofacitinib. Tofacitinib is an oral JAK inhibitor for the treatment of RA. We evaluated its effect on the immune response and safety of live zoster vaccine (LZV). In this phase II, 14-week, placebo-controlled trial, patients ages 50 years and older who had active RA and were receiving background methotrexate were given LZV and randomized to receive tofacitinib 5 mg twice daily or placebo 2-3 weeks postvaccination. We measured humoral responses (varicella zoster virus [VZV]-specific IgG level as determined by glycoprotein enzyme-linked immunosorbent assay) and cell-mediated responses (VZV-specific T cell enumeration, as determined by enzyme-linked immunospot assay) at baseline and 2 weeks, 6 weeks, and 14 weeks postvaccination. End points included the geometric mean fold rise (GMFR) in VZV-specific IgG levels (primary end point) and T cells (number of spot-forming cells/10 6 peripheral blood mononuclear cells) at 6 weeks postvaccination. One hundred twelve patients were randomized to receive tofacitinib (n = 55) or placebo (n = 57). Six weeks postvaccination, the GMFR in VZV-specific IgG levels was 2.11 in the tofacitinib group and 1.74 in the placebo group, and the VZV-specific T cell GMFR was similar in the tofacitinib group and the placebo group (1.50 and 1.29, respectively). Serious adverse events occurred in 3 patients in the tofacitinib group (5.5%) and 0 patients (0.0%) in the placebo group. One patient, who lacked preexisting VZV immunity, developed cutaneous vaccine dissemination 2 days after starting tofacitinib (16 days postvaccination). This resolved after tofacitinib was discontinued and the patient received antiviral treatment. Patients who began treatment with tofacitinib 2-3 weeks after receiving LZV had VZV-specific humoral and cell

Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib: an international, multicentre, prospective, randomised, placebo-controlled phase 3 trial (GRID)

Science.gov (United States)

Demetri, George D; Reichardt, Peter; Kang, Yoon-Koo; Blay, Jean-Yves; Rutkowski, Piotr; Gelderblom, Hans; Hohenberger, Peter; Leahy, Michael; von Mehren, Margaret; Joensuu, Heikki; Badalamenti, Giuseppe; Blackstein, Martin; Cesne, Axel Le; Schöffski, Patrick; Maki, Robert G; Bauer, Sebastian; Nguyen, Binh Bui; Xu, Jianming; Nishida, Toshirou; Chung, John; Kappeler, Christian; Kuss, Iris; Laurent, Dirk; Casali, Paolo

2013-01-01

Summary Background To date, only two agents, imatinib and sunitinib, have shown clinical benefit in patients with gastrointestinal stromal tumours (GISTs), but almost all metastatic GISTs eventually develop resistance to these agents, resulting in fatal disease progression. This phase 3 trial assessed efficacy and safety of regorafenib in patients with metastatic and/or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods Patients were randomised 2:1 to receive either regorafenib 160 mg orally daily or placebo, plus best supportive care in both arms, for the first 3 weeks of each 4-week cycle. The primary endpoint was progression-free survival (PFS). Upon disease progression, patients on placebo could cross over to regorafenib. Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR: rate of durable stable disease lasting for ≥12 weeks plus complete or partial responses), and safety. This trial is registered at ClinicalTrials.gov (NCT01271712). Results From January to August 2011, 240 patients were screened at 57 centres in 17 countries, and 199 patients were randomised to receive regorafenib (n=133) or matching placebo (n=66). Median PFS per independent blinded central review was 4·8 months and 0·9 months, respectively (hazard ratio [HR] 0·27, 95% confidence interval [CI] 0·19–0·39; pregorafenib, resulting in no significant difference in OS between study arms (HR 0·77, 95% CI 0·42–1·41; p=0·199). A best response of partial response or stable disease was observed in 101/133 patients (75·9%) on regorafenib and 23/66 patients (34·8%) on placebo. DCR was 52·6% (70/133 patients) and 9·1% (6/66 patients), respectively. Drug-related adverse events were reported in 130 (98·5%) of 132 regorafenib patients and 45 (68·2%) of 66 placebo patients. The most common grade ≥3 regorafenib-related adverse events were hypertension (31/132, 23·5%), hand–foot skin reaction (26

Increased eating control and energy levels associated with consumption of bitter orange (p-synephrine extract: a randomized placebo-controlled study

Directory of Open Access Journals (Sweden)

Kaats GR

2017-07-01

Full Text Available Gilbert R Kaats,1 Robert B Leckie,2 Nate Mrvichin,1 Sidney J Stohs3 1Integrative Health Technologies, Inc., 2R.B. Leckie Research Consultants, San Antonio, TX, 3Creighton University Medical Center, Omaha, NE, USA Abstract: Using a placebo-controlled double-blinded 30-day protocol, 40 overweight adults were asked to consume a chocolate-flavored chew 15–30 min before their two largest meals of the day. The chews contained either a placebo or an “active” product (100 mg of a bitter orange extract, standardized to 51.5 mg p-synephrine. Subjects completed a 13-item Weight Control Support Scale (WCSS containing eating control, energy level, and palatability subscales daily throughout the study. All 40 subjects completed the study. No adverse effects were reported in either the placebo or active groups. As compared to placebo, subjects consuming the active product reported statistically more (p≤0.001 positive responses on the WCSS as well as on each of the three subscales. This study suggests that, as compared to a placebo control, consuming a chew containing bitter orange extract (51.5 mg p-synephrine 15–30 min before the two largest meals of the day resulted in a statistically significant greater and more positive response to eating/appetite control and a weight-control support scale. Keywords: bitter orange extract, p-synephrine, Citrus aurantium, appetite suppression, energy, safety

Test of GERDA Phase II detector assembly

Energy Technology Data Exchange (ETDEWEB)

Bode, Tobias; Gusev, Konstantin [Technische Universitaet Muenchen (Germany); Schwingenheuer, Bernhard; Wagner, Victoria [Max-Planck Institut fuer Kernphysik, Heidelberg (Germany); Collaboration: GERDA-Collaboration

2014-07-01

The GERDA experiment searches for the lepton number violating neutrinoless double beta decay (0νββ) of {sup 76}Ge. The experiment uses HPGe detectors enriched in {sup 76}Ge as source and detection material. In GERDA Phase I five BEGe detectors were operated successfully. These detectors are distinguished for improved energy resolution and enhanced pulse shape discrimination (PSD) against background events. In Phase II additional 25 BEGe detectors will be installed. New electronics and radio-pure low-mass holders were specially designed for Phase II. Prior to the installation in GERDA all BEGe detectors are tested in their final assembly in the LNGS underground laboratory. This talk presents the mechanics and performance of the GERDA Phase II detector assembly.

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

Science.gov (United States)

Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates--a randomised double blind placebo controlled trial.

Directory of Open Access Journals (Sweden)

Sanjay Patole

Full Text Available BACKGROUND: Probiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort. AIM: To assess product quality, and confirm that Bifidobacterium breve (B. breve M-16V supplementation will increase fecal B. breve counts without adverse effects. METHODS AND PARTICIPANTS: Strain identity (16S rRNA gene sequencing, viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation <33 weeks ready to commence or on feeds for <12 hours were randomly allocated to either B. breve M-16V (3×109 cfu/day or placebo (dextrin supplementation until the corrected age 37 weeks. Stool samples were collected before (S1 and after 3 weeks of supplementation (S2 for studying fecal B. breve levels using quantitative PCR (Primary outcome. Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons. RESULTS: A total of 159 neonates (Probiotic: 79, Placebo: 80 were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%, S2: 25/66 (38%, p<0.001] Probiotic: [S1: 29/74 (40%, S2: 67/74 (91%, p<0.001]. Median S1 B. breve counts in both groups were below detection (<4.7 log cells x g(-1, increasing significantly in S2 for the probiotic group (log 8.6 while remaining <4.7 log in the control group (p<0.001. There were no adverse effects including probiotic sepsis and no deaths. NEC≥Stage II occurred in only 1 neonate (placebo group. CONCLUSION: B. breve M-16V is a suitable probiotic

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.

A randomized placebo-controlled study of noninvasive cortical electrostimulation in the treatment of fibromyalgia patients.

Science.gov (United States)

Hargrove, Jeffrey B; Bennett, Robert M; Simons, David G; Smith, Susan J; Nagpal, Sunil; Deering, Donald E

2012-01-01

The aim of this multicenter study was to evaluate the efficacy, safety, and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia (FM). A prospective, randomized, double-blind, placebo-controlled design was used. Setting.  Subjects received therapy at two different outpatient clinical locations. There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM. Intervention.  Thirty-nine (39) active treatment (AT) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period. The primary outcome measures were the number of tender points (TePs) and pressure pain threshold (PPT). Secondary outcome measures were responses to the Fibromyalgia Impact Questionnaire (FIQ), Symptom Checklist-90 (SCL-90), Beck Depression Inventory-II, and a novel sleep questionnaire, all evaluated at baseline and at the end of treatment. Intervention provided significant improvements in TeP measures: compared with placebo, the AT patients improved in the number of positive TePs (-7.4 vs -0.2, PFIQ score (-15.5 vs -5.6, P=0.03), FIQ pain (-2.0 vs -0.6, P=0.03), FIQ fatigue (-2.0 vs -0.4, P=0.02), and FIQ refreshing sleep (-2.1 vs -0.7, P=0.02); and while FIQ function improved (-1.0 vs -0.2), the between-group change had a 14% likelihood of occurring due to chance (P=0.14). There were no significant side effects observed. Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain, TeP measures, fatigue, and sleep; and the treatment was well tolerated. This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients. Wiley Periodicals, Inc.

Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Sagheb, Mohammad Mahdi; Dormanesh, Banafshe; Fallahzadeh, Mohammad Kazem; Akbari, Hamideh; Sohrabi Nazari, Sahar; Heydari, Seyed Taghi; Behzadi, Saeed

2012-05-01

Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial. Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase. Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1-11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5-4.8), (PVitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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.

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

Science.gov (United States)

Cuzick, Jack; Sestak, Ivana; Forbes, John F; Dowsett, Mitch; Knox, Jill; Cawthorn, Simon; Saunders, Christobel; Roche, Nicola; Mansel, Robert E; von Minckwitz, Gunter; Bonanni, Bernardo; Palva, Tiina; Howell, Anthony

2014-03-22

Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, pbreast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in

A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders.

Science.gov (United States)

Levin, Frances R; Mariani, John; Brooks, Daniel J; Pavlicova, Martina; Nunes, Edward V; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A; Carpenter, Kenneth M

2013-06-01

To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. The trial was conducted at two university research centers in the United States. One hundred and three cannabis-dependent adults participated in the trial. The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P marijuana use in the placebo group (F1,179  = 30.49, P depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. © 2013 Society for the Study of Addiction.

[The concept of placebo and the effect of placebo].

Science.gov (United States)

Göka, Erol

2002-01-01

The discussions about what placebo means and how its effect occurs go far back in the history of medicine. In general medicinal understanding, placebo means the subjective feeling of a positive effect in response to something that is used for curative intentions. In spite of difficulties in its definition and unknown content, its existence is generally accepted. What is discussed is its level of effectiveness in any disorder and medication. The placebo effect varies not only among diseases but also among regions and countries. Even the physicians' belief in a placebo increases its effect. Another interesting point about the placebo is its side effects. In many placebo controlled studies, the side effects of the placebo are found to be greater than those of real drugs. Different from other diseases, psychiatric disorders have strong connections with the placebo effect. The results of many studies support this idea. The increasing importance of placebos in psychiatry is really an interesting subject. For some people, the reason for this is hidden in the nature of psychiatric diseases. However, nonpharmacologic placebos such as "inspiration", "convincing", "confidence", and "belief" are believed to play a central role in psychiatry. In this article, placebo (the placebo effect) is defined, the implications of placebo in general medicine or psychiatry are discussed, and specific or nonspecific treatment methods are explained. The effects of a placebo on both the patient and the physician are emphasized. The significance of the placebo effect in psychiatry is also mentioned; and a new point of view, based upon the importance of symbolization and satisfaction is introduced in treatment and related action mechanisms.

Effect of paracetamol (acetaminophen and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690

Directory of Open Access Journals (Sweden)

Meijer Ron J

2003-02-01

Full Text Available Abstract Background Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. Methods Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. Results No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C. Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. Conclusions Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome.

Free-Piston Stirling Power Conversion Unit for Fission Power System, Phase II Final Report

Science.gov (United States)

Wood, J. Gary; Stanley, John

2016-01-01

In Phase II, the manufacture and testing of two 6-kW(sub e)Stirling engines was completed. The engines were delivered in an opposed 12-kW(sub e) arrangement with a common expansion space heater head. As described in the Phase I report, the engines were designed to be sealed both hermetically and with a bolted O-ring seal. The completed Phase II convertor is in the bolted configuration to allow future disassembly. By the end of Phase II, the convertor had passed all of the final testing requirements in preparation for delivery to the NASA Glenn Research Center. The electronic controller also was fabricated and tested during Phase II. The controller sets both piston amplitudes and maintains the phasing between them. It also sets the operating frequency of the machine. Details of the controller are described in the Phase I final report. Fabrication of the direct-current to direct-current (DC-DC) output stage, which would have stepped down the main controller output voltage from 700 to 120 V(sub DC), was omitted from this phase of the project for budgetary reasons. However, the main controller was successfully built, tested with the engines, and delivered. We experienced very few development issues with this high-power controller. The project extended significantly longer than originally planned because of yearly funding delays. The team also experienced several hardware difficulties along the development path. Most of these were related to the different thermal expansions of adjacent parts constructed of different materials. This issue was made worse by the large size of the machine. Thermal expansion problems also caused difficulties in the brazing of the opposed stainless steel sodium-potassium (NaK) heater head. Despite repeated attempts Sunpower was not able to successfully braze the opposed head under this project. Near the end of the project, Glenn fabricated an opposed Inconel NaK head, which was installed prior to delivery for testing at Glenn. Engine

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia

Science.gov (United States)

Rafii, Michael S.; Skotko, Brian G.; McDonough, Mary Ellen; Pulsifer, Margaret; Evans, Casey; Doran, Eric; Muranevici, Gabriela; Kesslak, Patrick; Abushakra, Susan; Lott, Ira T.

2018-01-01

Background ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer’s disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. Objective To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. Methods This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase 2 study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2:1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. Results There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram (ECG) results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. Conclusion Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy. PMID:28453471

Consistent and significant improvement of nighttime voiding frequency (nocturia) with silodosin in men with LUTS suggestive of BPH: pooled analysis of three randomized, placebo-controlled, double-blind phase III studies.

Science.gov (United States)

Eisenhardt, Andreas; Schneider, Tim; Cruz, Francisco; Oelke, Matthias

2014-10-01

Nocturia is prevalent and bothersome in men with lower urinary tract symptoms suggestive of BPH (LUTS/BPH). α-Adrenoceptor antagonists without subtype selectivity have inconsistently shown significant effects on nocturia in these patients. We explored the effects of the α1A-adrenoceptor subtype-selective antagonist silodosin on nocturia by analyzing three placebo-controlled registration studies. Responses to question 7 of the IPSS questionnaire were analyzed for the entire study population and patients with ≥ 2 voids/night at baseline. Improvement/worsening rates for nocturia were calculated for once-daily silodosin 8 mg and placebo. Silodosin effects on the mean number of nocturnal voids were compared with placebo, and the number of patients in whom nocturia was reduced to silodosin or placebo; 1,266 men (85 %) had ≥ 2 voids/night at baseline. Compared to placebo, more men treated with silodosin reported about nocturia improvement (53.4 vs. 42.8 %, p Silodosin significantly reduced nocturia within each study and pooled cohort compared to placebo (p silodosin and placebo had reductions of ≥ 1 voids/night, respectively (p = 0.0003), and significantly more patients with silodosin had nocturia episodes at study end compared to placebo (29.3 vs. 19.0 %; p = 0.0002). Although a weak impact on nocturia is already known from α-adrenoceptor antagonists without subtype selectivity, the individual placebo-controlled studies and the pooled data analysis showed that the α1A-adrenoceptor subtype-selective antagonist silodosin consistently and significantly improves nocturia in men with LUTS/BPH.

"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 (...

The impact of eszopiclone on sleep and cognition in patients with schizophrenia and insomnia: a double-blind, randomized, placebo-controlled trial.

Science.gov (United States)

Tek, Cenk; Palmese, Laura B; Krystal, Andrew D; Srihari, Vinod H; DeGeorge, Pamela C; Reutenauer, Erin L; Guloksuz, Sinan

2014-12-01

Insomnia is frequent in schizophrenia and may contribute to cognitive impairment as well as overuse of weight inducing sedative antipsychotics. We investigated the effects of eszopiclone on sleep and cognition for patients with schizophrenia-related insomnia in a double-blind placebo controlled study, followed by a two-week, single-blind placebo phase. Thirty-nine clinically stable outpatients with schizophrenia or schizoaffective disorder and insomnia were randomized to either 3mg eszopiclone (n=20) or placebo (n=19). Primary outcome measure was change in Insomnia Severity Index (ISI) over 8 weeks. Secondary outcome measure was change in MATRICS Consensus Cognitive Battery (MATRICS). Sleep diaries, psychiatric symptoms, and quality of life were also monitored. ISI significantly improved more in eszopiclone (mean=-10.7, 95% CI=-13.2; -8.2) than in placebo (mean=-6.9, 95% CI=-9.5; -4.3) with a between-group difference of -3.8 (95% CI=-7.5; -0.2). MATRICS score change did not differ between groups. On further analysis there was a significant improvement in the working memory test, letter-number span component of MATRICS (mean=9.8±9.2, z=-2.00, p=0.045) only for subjects with schizophrenia on eszopiclone. There were improvements in sleep diary items in both groups with no between-group differences. Psychiatric symptoms remained stable. Discontinuation rates were similar. Sleep remained improved during single-blind placebo phase after eszopiclone was stopped, but the working memory improvement in patients with schizophrenia was not durable. Eszopiclone stands as a safe and effective alternative for the treatment of insomnia in patients with schizophrenia. Its effects on cognition require further study. Copyright © 2014 Elsevier B.V. All rights reserved.

Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.

Science.gov (United States)

Thiele, Elizabeth A; Marsh, Eric D; French, Jacqueline A; Mazurkiewicz-Beldzinska, Maria; Benbadis, Selim R; Joshi, Charuta; Lyons, Paul D; Taylor, Adam; Roberts, Claire; Sommerville, Kenneth

2018-03-17

Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients. In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2-55 years) had Lennox-Gastaut syndrome, including a history of slow (caregivers, investigators, and individuals assessing data were masked to group assignment. The primary endpoint was percentage change from baseline in monthly frequency of drop seizures during the treatment period, analysed in all patients who received at least one dose of study drug and had post-baseline efficacy data. All randomly assigned patients were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02224690. Between April 28, 2015, and Oct 15, 2015, we randomly assigned 171 patients to receive cannabidiol (n=86) or placebo (n=85). 14 patients in the cannabidiol group and one in the placebo group discontinued study treatment; all randomly assigned patients received at least one dose of study treatment and had post-baseline efficacy data. The median percentage reduction in monthly drop seizure frequency from baseline was 43·9% (IQR -69·6 to -1·9) in the cannibidiol group and 21·8% (IQR -45·7 to 1·7) in the placebo group. The estimated median difference between the treatment groups was -17·21 (95% CI -30·32 to -4·09; p=0·0135) during the 14-week treatment period. Adverse events occurred in 74 (86%) of 86 patients in the cannabidiol group and 59 (69%) of

The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning

Science.gov (United States)

Świder, Karolina; Bąbel, Przemysław

2016-01-01

Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy. PMID:27362552

A randomized, placebo-controlled, preoperative trial of allopurinol in subjects with colorectal adenoma.

Science.gov (United States)

Puntoni, Matteo; Branchi, Daniela; Argusti, Alessandra; Zanardi, Silvia; Crosta, Cristiano; Meroni, Emanuele; Munizzi, Francesco; Michetti, Paolo; Coccia, Gianni; De Roberto, Giuseppe; Bandelloni, Roberto; Turbino, Laura; Minetti, Egle; Mori, Marco; Salvi, Sandra; Boccardo, Simona; Gatteschi, Beatrice; Benelli, Roberto; Sonzogni, Angelica; DeCensi, Andrea

2013-02-01

Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.

Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double-blind, placebo-controlled trials in adults with binge-eating disorder.

Science.gov (United States)

McElroy, Susan L; Hudson, James I; Gasior, Maria; Herman, Barry K; Radewonuk, Jana; Wilfley, Denise; Busner, Joan

2017-08-01

This study examined the time course of efficacy-related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol-defined moderate to severe binge-eating disorder (BED). In two 12-week, double-blind, placebo-controlled studies, adults meeting DSM-IV-TR BED criteria were randomized 1:1 to receive placebo or dose-optimized LDX (50 or 70 mg). Analyses across visits used mixed-effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE] scores, percentage body weight change) and chi-square tests (Clinical Global Impressions-Improvement [CGI-I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values binge eating days/week, binge-eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y-BOCS-BE total and domain scores. On the CGI-I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values Eating Disorders Published by Wiley Periodicals, Inc.

Chiral Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine and its Phase I and II Metabolites following Controlled Administration to Humans.

OpenAIRE

Steuer Andrea E; Schmidhauser Corina; Schmid Yasmin; Rickli Anna; Liechti Matthias E; Kraemer Thomas

2015-01-01

Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in blood have been performed after conjugate cleavage, without taking into account that phase II metabolites represent distinct chemical entities with their own effects and stereoselective pharmacokinetics. The aim of the present study was to stereoselectively investigate the pharmacokinetics of intact glucuronide and sulfate metabolites of MDMA in blood plasma after a controlled single MDMA dose. Plasma samples fr...

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial.

Science.gov (United States)

Sprigg, Nikola; Flaherty, Katie; Appleton, Jason P; Al-Shahi Salman, Rustam; Bereczki, Daniel; Beridze, Maia; Christensen, Hanne; Ciccone, Alfonso; Collins, Ronan; Czlonkowska, Anna; Dineen, Robert A; Duley, Lelia; Egea-Guerrero, Juan Jose; England, Timothy J; Krishnan, Kailash; Laska, Ann Charlotte; Law, Zhe Kang; Ozturk, Serefnur; Pocock, Stuart J; Roberts, Ian; Robinson, Thompson G; Roffe, Christine; Seiffge, David; Scutt, Polly; Thanabalan, Jegan; Werring, David; Whynes, David; Bath, Philip M

2018-05-26

Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic

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 ...

Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study.

Science.gov (United States)

Valenzuela, F; Paul, C; Mallbris, L; Tan, H; Papacharalambous, J; Valdez, H; Mamolo, C

2016-10-01

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. Psoriasis impacts on physical and psychological well-being; improvements in health-related quality of life (HRQoL) with etanercept in psoriasis are well documented. To evaluate HRQoL with tofacitinib, vs. placebo or etanercept, in the Phase 3, randomized, placebo-controlled, non-inferiority, Oral-treatment Psoriasis Trial (OPT) Compare Study (NCT01241591). Adults with moderate to severe chronic plaque psoriasis were randomized 3:3:3:1 to tofacitinib 10 or 5 mg twice daily (BID), etanercept 50 mg twice weekly or placebo, for 12 weeks. Patient-reported outcomes (PROs) included Dermatology Life Quality Index (DLQI), Itch Severity Item and Patient Global Assessment of psoriasis. At baseline, 83.4% (911/1092) of patients had a DLQI score ranging between 6 and 30, indicating a substantial burden of disease. By Week 12, 47.3%, 43.6% and 30.9% of patients in the tofacitinib 10 mg BID, etanercept and tofacitinib 5 mg BID groups, respectively, had a DLQI score of 0 or 1 (no effect of psoriasis on QoL) vs. 7.8% for placebo (all P Tofacitinib significantly reduced itch vs. placebo (P tofacitinib 10 mg BID, vs. etanercept, at Weeks 2-12 (all time points P tofacitinib 10 mg (68.6%) vs. etanercept (57.4%) and placebo (12.2%), and the PtGA response rate was significantly greater with tofacitinib 10 mg vs. placebo (P tofacitinib provided significant improvements across multiple PROs by Week 12. Improvements with tofacitinib 10 mg BID were comparable to etanercept, and improvements in itch were greater and more rapid with tofacitinib 10 mg BID. © 2016 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine.

Science.gov (United States)

Bayer, Otmar; Brémová, Tatiana; Strupp, Michael; Hüfner, Katharina

2018-02-01

Vestibular paroxysmia (VP) is characterized by short, often oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes provoked by turning the head. Despite the description of the disease almost 40 years ago (first termed "disabling positional vertigo"), no controlled treatment trial has been published to date. The Vestparoxy trial was designed as a randomized, placebo-controlled, double-blind cross-over trial to examine the therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable VP. Patients were recruited from August 2005 to December 2011 in the outpatient Dizziness Unit of the Department of Neurology of the Munich University Hospital, and randomized to receive OXA (first week: 300 mg once per day, second week: 300 mg b.i.d., third week: 300 mg t.i.d. until the end of the third month), followed by placebo or vice versa with a 1-month wash-out period in between. The primary endpoint was the number of days with one or more attacks. Secondary endpoints were the number of attacks during the observed days, and the median (for each day) duration of attacks. All these endpoints were assessed using standardized diaries collected at the end of each treatment phase. Forty-three patients were randomized, 18 patients provided usable data (2525 patient days) for at least one treatment phase and were included in the main (intention-to-treat) analysis. The most common reasons for discontinuation documented were adverse events. The risk of experiencing a day with at least one attack was 0.41 under OXA, and 0.62 under placebo treatment, yielding a relative risk of 0.67 (95% CI 0.47-0.95, p = 0.025). The number of attacks during the observed days ratio was 0.53 (95% CI 0.42-0.68, p effects.

Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers.

Science.gov (United States)

de Hoon, Jan; Van Hecken, Anne; Vandermeulen, Corinne; Herbots, Marissa; Kubo, Yumi; Lee, Ed; Eisele, Osa; Vargas, Gabriel; Gabriel, Kristin

2018-01-01

Objectives The aim of this study was to assess the effects of concomitant administration of erenumab and sumatriptan on resting blood pressure, pharmacokinetics, safety, and tolerability in healthy subjects. Methods In this phase 1, parallel-group, one-way crossover, double-blind, placebo-controlled study, healthy adult subjects were randomized (1:2) to receive either intravenous placebo and subcutaneous sumatriptan 12 mg (i.e. two 6-mg injections separated by 1 hour) or intravenous erenumab 140 mg and subcutaneous sumatriptan 12 mg. Blood pressure was measured pre-dose and at prespecified times post-dose. The primary endpoint was individual time-weighted averages of mean arterial pressure, measured from 0 hours to 2.5 hours after the first dose of sumatriptan. Pharmacokinetic parameters for sumatriptan were evaluated by calculating geometric mean ratios (erenumab and sumatriptan/placebo and sumatriptan). Adverse events and anti-erenumab antibodies were also evaluated. Results A total of 34 subjects were randomized and included in the analysis. Least squares mean (standard error) time-weighted averages of mean arterial pressure were 87.4 (1.0) mmHg for the placebo and sumatriptan group and 87.4 (1.2) mmHg for the erenumab and sumatriptan group. Mean difference in mean arterial pressure between groups was -0.04 mmHg (90% confidence interval: -2.2, 2.1). Geometric mean ratio estimates for maximum plasma concentration of sumatriptan was 0.95 (90% confidence interval: 0.82, 1.09), area under the plasma concentration-time curve (AUC) from time 0 to 6 hours was 0.98 (90% confidence interval: 0.93, 1.03), and AUC from time 0 to infinity was 1.00 (90% confidence interval: 0.96, 1.05). No clinically relevant safety findings for co-administration of sumatriptan and erenumab were identified. Conclusion Co-administration of erenumab and sumatriptan had no additional effect on resting blood pressure or on pharmacokinetics of sumatriptan. ClinicalTrials.gov, NCT

Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone.

Science.gov (United States)

Terra, Steven G; Focht, Kristen; Davies, Melanie; Frias, Juan; Derosa, Giuseppe; Darekar, Amanda; Golm, Gregory; Johnson, Jeremy; Saur, Didier; Lauring, Brett; Dagogo-Jack, Sam

2017-05-01

To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes. This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26. At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were -0.99% and -1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P  < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia. Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy. © 2017 John Wiley & Sons Ltd.

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.

129I Interlaboratory comparison: phase I and phase II

International Nuclear Information System (INIS)

Caffee, M. W.; Roberts, M. L.

1999-01-01

An interlaboratory comparison exercise for 129 I was organized and conducted. Nine laboratories participated in the exercise to either a full or limited extent. In Phase I of the comparison, 11 samples were measured. The suite of samples contained both synthetic ''standard type'' materials (i.e., AgI) and environmental materials. The isotopic 129 I/ 127 I ratios of the samples varied from 10 -8 to 10 -14 . In this phase, each laboratory was responsible for its own chemical preparation of the samples. In Phase I, the 129 I AMS measurements for prepared AgI were in good agreement. However, large discrepancies were seen in 129 I AMS measurements of environmental samples. Because of the large discrepancies seen in the Phase I 129 I intercomparison, a subsequent study was conducted. In Phase II of the 129 I intercomparison, three separate laboratories prepared AgI from two environmental samples (IAEA 375 soil and maples leaves). Each laboratory used its own chemical preparation method with each of the methods being distinctly different. The resulting six samples (two sets of three) were then re-distributed to the participating 129 I AMS facilities and 129 I/ 127 I ratios measured. Results and discussion of both the Phase I and Phase II interlaboratory comparison are presented

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...

A randomized Phase I/II Trial of HQK-1001, an oral fetal globin gene inducer, in β–thalassaemia intermedia and HbE/β–thalassaemia

Science.gov (United States)

Fucharoen, Suthat; Inati, Adlette; Siritanaratku, Noppadol; Thein, Swee Lay; Wargin, William C.; Koussa, Suzanne; Taher, Ali; Chaneim, Nattawara; Boosalis, Michael; Berenson, Ronald; Perrine, Susan P.

2014-01-01

β–thalassemia intermedia syndromes (BTI) cause hemolytic anemia, ineffective erythropoiesis, and widespread complications. Higher fetal globin expression within genotypes reduces globin imbalance and ameliorates anemia. Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty acid derivative, induces γ-globin expression experimentally and is well-tolerated in normal subjects. Accordingly, a randomized, blinded, placebo-controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with HbE/β0 thalassemia and 7 with β+/β0 thalassemia intermedia, to determine effective doses for fetal globin induction, safety, and tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at four dose levels (10, 20, 30, or 40 mg/kg/day), and subjects were monitored for laboratory and clinical events. Pharmacokinetic profiles demonstrated a t1/2 of 10–12 hours. Adverse events with HQK-1001 treatment were not significantly different from placebo treatment. Median HbF increased with the 20 mg/kg treatment doses above baseline levels by 6.6% and 0.44 g/dL (p <0.01) in 8/9 subjects; total hemoglobin (Hgb) increased by a mean of 1.1 gm/dL in 4/9 subjects. These findings identify a safe oral therapeutic which induces fetal globin in BTI. Further investigation of HQK-1001 with longer dosing to definitively evaluate its hematologic potential appears warranted. PMID:23530969

The Mobile Limiters of TJ-II: Power and Particle Control

International Nuclear Information System (INIS)

Cal, E. de la

1998-01-01

For mobile limiters have been designed for the TJ-II stellerator to reduce thermal loads on the vacuum vessel and its protections at the region of the central hard core (groove) and to characterise the scrap off layer plasma. The role of the mobile limiters for particle and thermal load control is analysed for the different operating phases of TJ-II. The task of impurity control will be treated in a future report. A simplified model has been used to estimate the termal loads on the limiters. The conclusion is that a new design for the limiter heads will be necessary for the neutral beam injection (NBI)-phase at high power density, if acceptable efficiencies of thermal removal is desired. The rexperimental measurements which will be made in the first phase (ECH) with the temperature and Lagmuir probes installed in the diagnosed limiter-heads will be essential for the optimisation of the future limiter-shape. For particle control it will be absolutely necessary to use first wall conditioning techniques (e.g. boronization), since no active pumping method is foreseen for TJ-II. Again, this point will be more critical in the NBI-phase, due to the large particle fluxes to the first wall and due to possible thermal gas, desorption caused by local overheating of plasma-facing surfaces. The role of magnetic topology on plasma-wall interaction is finally analysed. A configuration has been found in which the limiters act as divertor plates (Natural Island Divertor). This inherent flexibility for changing the magnetic topology of TJ-II should be exploited in order to find the most favourable operating scenarios for the high powder injection phase

Oral sumatriptan for migraine in children and adolescents: a randomized, multicenter, placebo-controlled, parallel group study.

Science.gov (United States)

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

A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

Science.gov (United States)

Schoenberg, Mike R; Rum, Ruba S; Osborn, Katie E; Werz, Mary Ann

2017-09-01

The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance. Wiley Periodicals, Inc. © 2017 International

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)

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

Science.gov (United States)

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

Upgrade for Phase II of the Gerda experiment

Science.gov (United States)

Agostini, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hiller, R.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Ioannucci, L.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kermaïdic, Y.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Nisi, S.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Ransom, C.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schütz, A.-K.; Schulz, O.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zsigmond, A. J.; Zuber, K.; Zuzel, G.

2018-05-01

The Gerda collaboration is performing a sensitive search for neutrinoless double beta decay of ^{76}Ge at the INFN Laboratori Nazionali del Gran Sasso, Italy. The upgrade of the Gerda experiment from Phase I to Phase II has been concluded in December 2015. The first Phase II data release shows that the goal to suppress the background by one order of magnitude compared to Phase I has been achieved. Gerda is thus the first experiment that will remain "background-free" up to its design exposure (100 kg year). It will reach thereby a half-life sensitivity of more than 10^{26} year within 3 years of data collection. This paper describes in detail the modifications and improvements of the experimental setup for Phase II and discusses the performance of individual detector components.

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

Science.gov (United States)

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.

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.

Effectiveness of Topical Sucralfate in the Management of Pressure Ulcer in Hospitalized Patients: A Prospective, Randomized, Placebo-Controlled Trial.

Science.gov (United States)

Ala, Shahram; Saeedi, Majid; Gholipour, Afshin; Ahmadi, Motahareh; Asoodeh, Ali; Shiva, Afshin

2018-04-10

The aim of this study was to evaluate the effectiveness of topical sucralfate in the management of pressure ulcer (PU) in hospitalized patients. Forty hospitalized patients with stage II PU were included in this prospective, double-blind, randomized, placebo-controlled trial and were randomly divided into 2 groups receiving either sucralfate gel or placebo, on a daily basis. The patients were visited every day for 14 days, the ulcer was evaluated using the Pressure Ulcer Scale for Healing (PUSH) and changes to the measured scores over time were used as an indicator of wound healing. There were no statistically significant differences in any of the demographic characteristics between both groups. Both of the interventions reduced the average PUSH score, and at the end of the trial, all but 2 patients were healed. One in each group discontinued the trial because of exacerbation of the ulcer. No significant between-group difference in the average PUSH score reduction was observed (6.36 ± 2.11 vs. 5.89 ± 1.41, P = 0.42). Although the average healing time was less in the sucralfate group (6.05 ± 2.17 vs. 7.78 ± 3.42), the difference was not statistically significant (P = 0.07). Sucralfate gel does not improve healing of PU compared with placebo.

40 CFR 72.73 - State issuance of Phase II permits.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State issuance of Phase II permits. 72.73 Section 72.73 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits...

Status of the Gerda phase II experiment

Energy Technology Data Exchange (ETDEWEB)

Lazzaro, Andrea [Physik-Department and Excellence Cluster Universe, Technische Universitaet Muenchen (Germany); Collaboration: GERDA-Collaboration

2016-07-01

The Gerda experiment searches for the neutrinoless double beta decay (0νββ) in {sup 76}Ge. The first phase of the experiment collected 21.6 kg. yr of exposure with a background index (BI) of 0.01 cts/(keV . kg . yr). No signal was observed and a lower limit for the 0νββ half-life was set to T{sup 0νββ}{sub 1/2} < 2.1 . 10{sup 25} yr (90% C.L). The apparatus has now been upgraded to the Phase II configuration. In Phase II 38 kg of HPGe detectors will be operated to reach an exposure of 100 kg . yr. The goal of Gerda Phase II is to lower the BI to 10{sup -3} cts/(keV . kg . y), in order to reach the sensitivity for T{sup 0νββ}{sub 1/2} = O(10{sup 26}) yr. The additional target mass is constituted of 30 custom made BEGe detectors with higher energy resolution and better pulse shape discrimination performance. The detectors are operated in new radio-pure low-mass holders. The liquid argon surrounding the detectors has been instrumented to veto the background events which produce scintillation light. In this talk the current status and the performance of the Gerda Phase II are presented.

Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

2016-03-01

Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial.

Science.gov (United States)

Abe, Masatoshi; Nishigori, Chikako; Torii, Hideshi; Ihn, Hironobu; Ito, Kei; Nagaoka, Makoto; Isogawa, Naoki; Kawaguchi, Isao; Tomochika, Yukiko; Kobayashi, Mihoko; Tallman, Anna M; Papp, Kim A

2017-11-01

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Lunar Health Monitor, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — During the Phase II Lunar Health Monitor program, Orbital Research will develop a second generation wearable sensor suite for astronaut physiologic monitoring. The...

78 FR 76789 - Additional Connect America Fund Phase II Issues

Science.gov (United States)

2013-12-19

... inspection and copying during normal business hours in the FCC Reference Information Center, Portals II, 445... Phase I to Phase II. 2. Timing of Phase II Support Disbursements. In the USF/ICC Transformation Order... language in paragraph 180 of the USF/ICC Transformation Order. We now seek to more fully develop the record...

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent; Delaloge, Suzette; Moy, Beverly; Iwata, Hiroji; von Minckwitz, Gunter; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Tomašević, Zorica; Denduluri, Neelima; Šeparović, Robert; Gokmen, Erhan; Bashford, Anna; Ruiz Borrego, Manuel; Kim, Sung-Bae; Jakobsen, Erik Hugger; Ciceniene, Audrone; Inoue, Kenichi; Overkamp, Friedrich; Heijns, Joan B; Armstrong, Anne C; Link, John S; Joy, Anil Abraham; Bryce, Richard; Wong, Alvin; Moran, Susan; Yao, Bin; Xu, Feng; Auerbach, Alan; Buyse, Marc; Chan, Arlene

2017-12-01

ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib

Probability of success for phase III after exploratory biomarker analysis in phase II.

Science.gov (United States)

Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver

2017-05-01

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.

Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

Science.gov (United States)

Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

2012-09-07

In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial.

Science.gov (United States)

Amen, Daniel G; Taylor, Derek V; Ojala, Kristine; Kaur, Jasleen; Willeumier, Kristen

2013-01-01

Cog (cognitive performance), the WebNeuro (emotional state), and three psychological inventories-the Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI), and Quality of Life Inventory (QOLI). A region of interest (ROI) analysis for each of the 2-mo phases (baseline, then placebo and treatment according to randomized order) showed significant improvement in rCBF for the BDNs as compared to the placebo (as assigned at the start of the first intervention) in the prefrontal cortex, anterior and posterior cingulate gyrus, hippocampus, and cerebellum. Significant improvements were observed for the BDNs (1) on the MicroCog-reasoning, P=.008; memory, P=.014; information processing accuracy, P=.027; (2) on the WebNeuro-executive function, P=.002, information processing efficiency, P=.015; depressed mood, P=.017, and emotional identification, P=.041; and (3) on the BSI-positive symptom total, P=.024 and reduced hostility, P=.018. For the last, significance occurred upon accounting for the effect of order. This study demonstrates the potential effectiveness of BDNs in enhancing rCBF and neuropsychological function across various cognitive and psychological domains.

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

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

Science.gov (United States)

Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki S; Ismail, Hussain Imam H J Muhammad; Chotpitayasunondh, Tawee; Chua, Mary Noreen; Luong, Chan Quang; Rusmil, Kusnandi; Wirawan, Dewa Nyoman; Nallusamy, Revathy; Pitisuttithum, Punnee; Thisyakorn, Usa; Yoon, In-Kyu; van der Vliet, Diane; Langevin, Edith; Laot, Thelma; Hutagalung, Yanee; Frago, Carina; Boaz, Mark; Wartel, T Anh; Tornieporth, Nadia G; Saville, Melanie; Bouckenooghe, Alain

2014-10-11

An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse

BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

Directory of Open Access Journals (Sweden)

Larsen S

2014-11-01

Full Text Available Stig Larsen,1 Kritiya Butthongkomvong,2 Alexey Manikhas,3 Ekaterina Trishkina,4 Elena Poddubuskaya,5 Marina Matrosova,6 Vichien Srimuninnimit,7 Steen Lindkær-Jensen81Department of Controlled Clinical Trials and Biostatistics, Centre for Epidemiology and Biostatistics, University of Life Science, Oslo, Norway; 2Udonthani Cancer Hospital, Udonthani, Thailand; 3Department of Oncology, City Clinical Oncology, Dispensary, St Petersburg, Russia; 4Department of Oncology, Leningrad Regional Oncology Centre, St Petersburg, Russia; 5Department of Oncology, Unit of Russian Academy of Medical Science, Moscow, Russia; 6Department of Oncology, N Novgorod Regional Oncology Dispensary, Novgorod, Russia; 7Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 8Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UKAbstract: The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II dichloride (BP-C1 versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer.Material and methods: A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI, European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23 data were recorded at

Oxygen-Methane Thruster, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Two main innovations will be developed in the Phase II effort that are fundamentally associated with our gaseous oxygen/gaseous methane RCS thruster. The first...

The effect of Lactobacillus brevis KB290 against irritable bowel syndrome: a placebo-controlled double-blind crossover trial

Directory of Open Access Journals (Sweden)

Murakami Katsumi

2012-08-01

Full Text Available Abstract Background Irritable bowel syndrome (IBS is a functional disorder of the digestive tract that causes chronic abdominal symptoms. We evaluated the effects of Lactobacillus brevis KB290 (KB290, which has been demonstrated to be effective at improving bowel movements and the composition of intestinal microflora, on IBS symptoms. Methods We performed a placebo control double-blind cross matched trial. Thirty-five males and females (aged 6 years and above who had been diagnosed with IBS according to the Rome III criteria were divided into 2 groups, and after a 4-week pre-trial observation period, they were administered test capsules containing KB290 or placebo for 4 weeks (consumption period I. Then, the capsule administration was suspended for 4 weeks in both groups (washout period, before the opposite capsules were administered for a further 4 weeks (consumption period II. Fecal samples were collected on the first day of the pre-consumption observation period, the last day of consumption period I, the last day of the washout period, and the last day of consumption period II. In addition, the subjects’ IBS symptoms and quality of life (QOL and any adverse events that they experienced were evaluated. Results No significant difference in IBS symptoms was noted among the various periods. However, the mean QOL scores were improved during the test capsule consumption. The frequencies of watery and mushy feces were significantly lower in the test capsule consumption period than during the pre-consumption observation period, and the frequency of abdominal pain was significantly reduced in the test capsule consumption period compared with the other periods. The frequency of the genus Bifidobacterium was significantly higher, and that of the genus Clostridium was significantly lower, after the test capsule consumption than after the placebo consumption. The frequencies of the genera Lactobacillus, Bacteroides, and Enterococcus were also

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

Directory of Open Access Journals (Sweden)

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

Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials

DEFF Research Database (Denmark)

Barbour, S; Smit, T.; Wang, X

2017-01-01

adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data...... cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined...... for treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828...

OSAS Surgery and Postoperative Discomfort: Phase I Surgery versus Phase II Surgery

Directory of Open Access Journals (Sweden)

Giulio Gasparini

2015-01-01

Full Text Available Introduction. This study aims to investigate the reasons that discourage the patients affected by OSAS to undergo orthognathic surgery and compares the postoperative discomfort of phase I (soft tissue surgery and phase II (orthognathic surgery procedures for treatment of OSAS. Material and Methods. A pool of 46 patients affected by OSAS was divided into two groups: “surgery patients” who accepted surgical treatments of their condition and “no surgery patients” who refused surgical procedures. The “surgery patients” group was further subdivided into two arms: patients who accepted phase I procedures (IP and those who accepted phase II (IIP. To better understand the motivations behind the refusal of II phase procedures, we asked the patients belonging to both the IP group and “no surgery” group to indicate the main reason that influenced their decision to avoid II phase procedures. We also monitored and compared five parameters of postoperative discomfort: pain, painkiller assumption, length of hospitalization, foreign body sensation, and diet assumption following IP and IIP procedures. Results. The main reason to avoid IIP procedures was the concern of a more severe postoperative discomfort. Comparison of the postoperative discomfort following IP versus IIP procedures showed that the former scored worse in 4 out of 5 parameters analyzed. Conclusion. IIP procedures produce less postoperative discomfort. IIP procedures, namely, orthognathic surgery, should be the first choice intervention in patients affected by OSAS and dentoskeletal malformation.

A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.

Science.gov (United States)

Wilens, Timothy E; Robertson, Brigitte; Sikirica, Vanja; Harper, Linda; Young, Joel L; Bloomfield, Ralph; Lyne, Andrew; Rynkowski, Gail; Cutler, Andrew J

2015-11-01

Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132. Copyright © 2015. Published by Elsevier Inc.

Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Whitehorn, James; Nguyen, Chau Van Vinh; Khanh, Lam Phung; Kien, Duong Thi Hue; Quyen, Nguyen Than Ha; Tran, Nguyen Thi Thanh; Hang, Nguyen Thuy; Truong, Nguyen Thanh; Hue Tai, Luong Thi; Cam Huong, Nguyen Thi; Nhon, Vo Thanh; Van Tram, Ta; Farrar, Jeremy; Wolbers, Marcel; Simmons, Cameron P; Wills, Bridget

2016-02-15

Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy. Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms. Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures. We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.Chinese Clinical Trials Registration. ISRCTN03147572. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Placebo controlled comparison of the opioid sparing effect of meloxicam and diclofenac after abdominal hysterectomy

International Nuclear Information System (INIS)

Anwari, Jamil S.; Anjum, S.; Al-Khunain, S.

2008-01-01

Objective was to compare the opioid sparing effect of meloxicam and diclofenac after abdominal hysterectomy. This study was conducted at the Riyadh Military Hospital, Kingdom of Saudi Arabia from February 2004 to November 2006. Women of American Society of Anesthesiologist's classification I or II of ages 25-60 years scheduled for abdominal hysterectomy were included. Those with significant systematic disease or contraindication to opioid or non-steroidal anti-inflammatory drugs were excluded from the study. All patients received general anesthesia and intravenous (IV) morphine and were intubated and ventilated for the operation. The patients were randomized and rectally received meloxicam (15 mg), diclofenac (100 mg) or placebo suppository. Patients, postoperatively blinded were blinded to these drugs. In the recover room, (IV) patient controlled morphine was commenced. The information sought included patient characteristic (age, weight), duration operation and doses of morphine consumed in 24 hours. Seventy-five patients (25 in each group) participated in this study and only 5 patients dropped out. There was no difference in age and body weight of the patients and duration of operation. All underwent either total or sub-total hysterectomy. The mean (SD) morphine consumption in the 24 hour postoperative period was 37.7 (11.1) mg for the diclofenac group, 40.1 (7.8) mg for the meloxicam group and 45.2 (9.8) mg for the placebo group. As compared to placebo, the mean morphine consumption in diclofenac (but not in meloxicam) group was significantly (p<0.05) reduced. Our study demonstrates a significant opioid sparing effect after abdominal hysterectomy with diclofenac but not with meloxicam. (author)

A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal.

Science.gov (United States)

Gorodetzky, Charles W; Walsh, Sharon L; Martin, Peter R; Saxon, Andrew J; Gullo, Kristen L; Biswas, Kousick

2017-07-01

Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop - time curve (i.e., AUC 1-5 ), and daily mean SOWS-Gossop, OOWS-Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2mg daily in four divided doses or matching placebo on Days 1-5, followed by 2days of placebo. Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p=0.0212. Fewer lofexidine patients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p=0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms. Copyright © 2017. Published by Elsevier B.V.

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.

A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.

Directory of Open Access Journals (Sweden)

Luciana Cadore Stefani

Full Text Available Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT and the pressure pain tolerance (PPTo. Quantitative sensory testing (QST was used to measure the heat pain threshold (HPT and the heat pain tolerance (HPTo. Sedation was assessed with a visual analogue scale and bispectral analysis.Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg and the highest (0.25 mg/kg melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R(2  = 0.492 for HPT, R(2  = 0.538 for PPT, R(2  = 0.558 for HPTo and R(2  = 0.584 for PPTo.The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec: (U1111

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

Directory of Open Access Journals (Sweden)

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.

Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study.

Science.gov (United States)

Donnenfeld, Eric D; Karpecki, Paul M; Majmudar, Parag A; Nichols, Kelly K; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P

2016-06-01

To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events.

Barriers to participation in a phase II cardiac rehabilitation programme.

Science.gov (United States)

Mak, Y M W; Chan, W K; Yue, C S S

2005-12-01

To identify barriers to participation in a phase II cardiac rehabilitation programme and measures that may enhance participation. Prospective study. Regional hospital, Hong Kong. Cardiac patients recruited for a phase I cardiac rehabilitation programme from July 2002 to January 2003. Reasons for not participating in a phase II cardiac rehabilitation programme. Of the 193 patients recruited for a phase I cardiac rehabilitation programme, 152 (79%) patients, with a mean age of 70.3 years (standard deviation, 11.9 years), did not proceed to phase II programme. Eleven (7%) deaths occurred before commencement of phase II and 74 (49%) patients were considered physically unfit. Reasons for the latter included fractures, pain, or degenerative changes in the lower limbs (24%), and co-morbidities such as cerebrovascular accident (19%), chronic renal failure (11%), congestive heart failure (9%), and unstable angina (8%). Phase II rehabilitation was postponed until after completion of scheduled cardiac interventions in 13% of patients. Failure of physicians to arrange the pre-phase II exercise stress test as per protocol was reported in 7% of patients. Other reasons were reported: work or time conflicts (16%), non-compliance with cardiac treatment (5%), financial constraints (4%), self-exercise (3%), fear after exercise stress testing (3%), and patients returning to their original cardiologists for treatment (3%). A significant (79%) proportion of patients did not proceed to a phase II cardiac rehabilitation programme for a variety of reasons. These included physical unfitness, work or time conflicts, and need to attend scheduled cardiac interventions. Further studies are required to determine how to overcome obstacles to cardiac rehabilitation.

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

DEFF Research Database (Denmark)

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....

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

Science.gov (United States)

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.

Science.gov (United States)

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.

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

Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).

Science.gov (United States)

Bella, Eleonora Dalla; Tramacere, Irene; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; Bella, Vincenzo La; Lunetta, Christian; Mandrioli, Jessica; Mazzini, Letizia; Messina, Sonia; Monsurrò, Maria Rosaria; Mora, Gabriele; Riva, Nilo; Rizzi, Romana; Siciliano, Gabriele; Silani, Vincenzo; Simone, Isabella; Sorarù, Gianni; Volanti, Paolo; Lauria, Giuseppe

2017-08-11

Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumulation and endoplasmic reticulum overload. Guanabenz proved to rescue motoneurons from misfolding protein stress both in in vitro and in vivo ALS models, making it a potential disease-modifying drug in patients. It is conceivable investigating whether its neuroprotective effects based on the inhibition of eIF2α dephosphorylation can change the progression of ALS. Protocolised Management In Sepsis is a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial with futility design. We will investigate clinical outcomes, safety, tolerability and biomarkers of neurodegeneration in patients with ALS treated with guanabenz or riluzole alone for 6 months. The primary aim is to test if guanabenz can reduce the proportion of patients progressed to a higher stage of disease at 6 months compared with their baseline stage as measured by the ALS Milano-Torino Staging (ALS-MITOS) system and to the placebo group. Secondary aims are safety, tolerability and change in at least one biomarker of neurodegeneration in the guanabenz arm compared with the placebo group. Findings will provide reliable data on the likelihood that guanabenz can slow the course of ALS in a phase III trial. The study protocol was approved by the Ethics Committee of IRCCS 'Carlo Besta Foundation' of Milan

The Addition of Platelet-Rich Plasma to Facial Lipofilling: A Double-Blind, Placebo-Controlled, Randomized Trial.

Science.gov (United States)

Willemsen, Joep C N; Van Dongen, Joris; Spiekman, Maroesjka; Vermeulen, Karin M; Harmsen, Martin C; van der Lei, Berend; Stevens, H P Jeroen

2018-02-01

Lipofilling is a treatment modality to restore tissue volume, but it may also rejuvenate the aging skin. Platelet-rich plasma has been reported to augment the efficacy of lipofilling, both on graft take and rejuvenation, by altering the adipose-derived stem cells. The authors hypothesized that addition of platelet-rich plasma would increase the rejuvenating effect and shorten recovery time. The study conducted was a single-center, double-blind, placebo-controlled, randomized trial (2012 to 2015). In total, a well-defined cohort of 32 healthy female patients enrolled in the study, with 25 completing the follow-up. All patients underwent aesthetic facial lipofilling with either saline or platelet-rich plasma added. Outcome was determined by changes in skin elasticity, volumetric changes of the nasolabial fold, recovery time, and patient satisfaction during follow-up (1 year). Platelet-rich plasma did not improve the outcome of facial lipofilling when looking at skin elasticity improvement, graft volume maintenance in the nasolabial fold. Reversal of the correlation between age and elasticity, however, might suggest a small effect size, and thus might not be significant with our small study population. This randomized, double-blind, placebo-controlled study clearly has shown that platelet-rich plasma significantly reduces postoperative recovery time but does not improve patient outcome when looking at skin elasticity, improvement of the nasolabial fold, or patient satisfaction. The reversal of the correlation between age and elasticity might indicate some effect on skin but requires more power in future studies. Therapeutic, II.

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

Science.gov (United States)

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or

A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

Science.gov (United States)

Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

2016-11-15

Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Data from four double-blind placebo-controlled pivotal phase III clinical studies.

Science.gov (United States)

Elger, Christian; Koepp, Mathias; Trinka, Eugen; Villanueva, Vicente; Chaves, João; Ben-Menachen, Elinor; Kowacs, Pedro A; Gil-Nagel, António; Moreira, Joana; Gama, Helena; Rocha, José-Francisco; Soares-da-Silva, Patrício

2017-12-01

Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures. Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (≥50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments. SSF was significantly reduced with ESL 800 mg (P ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs (AED). Incidence of adverse events (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability. © 2017 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

Science.gov (United States)

Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

2012-09-01

A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study

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

Directory of Open Access Journals (Sweden)

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.

Placebo can enhance creativity.

Science.gov (United States)

Rozenkrantz, Liron; Mayo, Avraham E; Ilan, Tomer; Hart, Yuval; Noy, Lior; Alon, Uri

2017-01-01

The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition. Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency. The placebo group showed higher originality than the control group both in the CFG (pcreativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity.

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

Science.gov (United States)

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.

First results from GERDA Phase II

Science.gov (United States)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-09-01

Gerda is designed for a background-free search of 76Ge neutrinoless double-β decay, using bare Ge detectors in liquid Ar. The experiment was upgraded after the successful completion of Phase I to double the target mass and further reduce the background. Newly-designed Ge detectors were installed along with LAr scintillation sensors. Phase II of data-taking started in Dec 2015 with approximately 36 kg of Ge detectors and is currently ongoing. The first results based on 10.8 kg· yr of exposure are presented. The background goal of 10-3 cts/(keV· kg· yr) is achieved and a search for neutrinoless double-β decay is performed by combining Phase I and II data. No signal is found and a new limit is set at T1/20ν > 5.3 \\cdot {1025} yr (90% C.L.).

Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

Science.gov (United States)

de los Santos, A R; Zmijanovich, R; Pérez Macri, S; Martí, M L; Di Girolamo, G

2001-01-01

We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

Results from a pooled analysis of two European, randomized, placebo-controlled, phase 3 studies of ATX-101 for the pharmacologic reduction of excess submental fat.

Science.gov (United States)

McDiarmid, James; Ruiz, Jesus Benito; Lee, Daniel; Lippert, Susanne; Hartisch, Claudia; Havlickova, Blanka

2014-10-01

The injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies. Patients with unwanted SMF were randomized to receive 1 or 2 mg/cm(2) of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded. Significantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, and 28.6 % of the placebo recipients; p < 0.001 for both ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 34.3 % of the placebo recipients; p < 0.001 for both), analyzed alone or in combination, with ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm(2), respectively, vs. 29.0 % of the placebo recipients; p < 0.001 for both). In this study, ATX-101 was effective irrespective of

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...

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

Science.gov (United States)

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.

Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

Science.gov (United States)

Gong, Fen; Niu, Junzhi; Pei, Xing

2016-11-02

Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-β, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

Science.gov (United States)

Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

2015-09-01

Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355

Má oclusão Classe II de Angle tratada sem extrações e com controle de crescimento Angle Class II malocclusion treated without extractions and with growth control

Directory of Open Access Journals (Sweden)

Flávia Artese

2009-06-01

Full Text Available A má oclusão Classe II de Angle é caracterizada por uma discrepância dentária anteroposterior, que geralmente está acompanhada por alterações esqueléticas. O tratamento ortodôntico precoce permite a correção da discrepância esquelética por controle de crescimento (primeira fase, o que favorece a correção do posicionamento dentário, mais tardiamente (segunda fase. Este relato descreve o tratamento de um caso de má oclusão Classe II, divisão 2, de Angle, em duas fases, e foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO, como parte dos requisitos para a obtenção do título de Diplomado pelo BBO. O caso foi avaliado como representante da Categoria 1, ou seja, má oclusão Classe II de Angle tratada sem extrações dentárias e com controle de crescimento.Angle Class II malocclusion is characterized by an anteroposterior dental discrepancy which is generally accompanied by skeletal disharmonies. Early orthodontic treatment allows the correction of skeletal discrepancies using growth control (first phase which favors later correction of tooth positioning (second phase. This case report describes an Angle Class II, division 2, malocclusion treated in two phases and was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO as part of the requirements for BBO certification. It was evaluated as a Category 1 case, i.e., Class II malocclusion treated without extractions, with growth control.

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia

DEFF Research Database (Denmark)

Pauer, Lynne; Winkelmann, Andreas; Arsenault, Pierre

2011-01-01

To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.......To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States....

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.

Effects of angiotensin II blockade on intermediate cardiovascular endpoints in haemodialysis patients: a randomised double-blind placebo-controlled one-year intervention trial (SAFIR study)

DEFF Research Database (Denmark)

Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam

Agents blocking the renin-angiotensin-aldosterone system are frequently used in end-stage renal disease patients, but whether they exert beneficial cardiovascular (CV) effects is unclear. The long-term effects of the angiotensin II receptor blocker irbesartan was investigated in 82 haemodialysis...... renal function. Brachial BP decreased significantly in both groups, but there was no significant difference between placebo and irbesartan treated. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different in the two groups. Intermediate CV endpoints...... such as central aortic BP, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal prohormone of brain natriuretic peptide, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic BP during the study period correlated...

Adding Fludarabine to Cyclophophamide-dexamethason induction therapy impair stem cell harvest in MM

DEFF Research Database (Denmark)

Johnsen, Hans Erik; Meldgaard Knudsen, Lene; Mylin, Anne Kærsgaard

BACKGROUND AND OBJECTIVES Recent data have indicated that the myeloma cell hierarchy includes resistant Recent data have indicated that the myeloma cell hierarchy includes resistant circulating clonal memory B cells, which differ considerably from the classical end stage plasma cells infiltrating......, placebo controlled, single blinded, phase II study evaluating This was a randomized, placebo controlled, single blinded, phase II study evaluating toxicity and safety of Fludarabine added to Cyclophosphamide and Dexamethasone (CyDex) as induction therapy in younger patients with untreated and treatment...

SIMMER-II analysis of transition-phase experiments

International Nuclear Information System (INIS)

Wehner, T.R.; Bell, C.R.

1985-01-01

Analyses of Los Alamos transition-phase experiments with the SIMMER-II computer code are reported. These transient boilup experiments simulated the recriticality-induced transient motion of a boiling pool of molten fuel, molten steel and steel vapor, within a subassembly duct in a liquid-metal fast breeder reactor during the transition phase of a core-disruptive accident. The two purposes of these experiments were to explore and reach a better understanding of fast reactor safety issues, and to provide data for SIMMER-II verification. Experimental data, consisting of four pressure traces and a high-speed movie, were recorded for four sets of initial conditions. For three of the four cases, SIMMER-II-calculated pressures compared reasonably well with the experimental pressures. After a modification to SIMMER-II's liquid-vapor drag correlation, the comparison for the fourth case was reasonable also. 12 refs., 4 figs

Pain relief of sore throat with a new anti-inflammatory throat lozenge, ibuprofen 25 mg: A randomised, double-blind, placebo-controlled, international phase III study.

Science.gov (United States)

Bouroubi, Athmane; Donazzolo, Yves; Donath, Franck; Eccles, Ron; Russo, Marc; Harambillet, Nadine; Gautier, Stéphanie; Montagne, Agnès

2017-09-01

The aim of this study was to compare the efficacy and safety of a new oromucosal ibuprofen form, ibuprofen 25 mg lozenge, in single and repeat dosing for up to 4 days, to the matched placebo, in the treatment of acute sore throat pain in adults. In this randomised, double-blind, placebo-controlled trial, adult patients with non-streptococcal sore throat and signs of moderate-to-severe associated pain (≥5 on the objective Tonsillo-Pharyngitis Assessment 21-point scale and ≥60 mm on the subjective 0-100 mm visual analogue Sore Throat Pain Intensity Scale [STPIS]) were assigned ibuprofen 25 mg (n=194) or matching placebo (n=191) lozenge treatment. Efficacy was assessed (at the investigating centre up to 2 hours after first dosing, then on an ambulatory basis) by parameters derived from patient's scores on scales of pain relief, pain intensity, and global efficacy assessment. The primary efficacy end-point was the time-weighted TOTal PAin Relief (TOTPAR) over 2 hours after first dosing using the Sore Throat Relief Scale (STRS). Safety and local tolerability were assessed. Ibuprofen 25 mg was superior to placebo on numerous pain relief parameters; TOTPAR was significantly higher with ibuprofen 25 mg over 2 hours after first dosing (Ppain (n=128), after an average 4 days (Prelief of sore throat pain and is as well tolerated as placebo. ClinicalTrials.gov, NCT01785862. © 2017 John Wiley & Sons Ltd.

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

Science.gov (United States)

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

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...

Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a double-blind, placebo-controlled trial.

Science.gov (United States)

Simon, James A; Archer, David F; Kagan, Risa; Bernick, Brian; Graham, Shelli; Constantine, Ginger D; Mirkin, Sebastian

2017-09-01

To evaluate the response of the vaginal mucosa with TX-004HR and its correlation with vulvar and vaginal atrophy (VVA) symptoms, and whether visual examination is a useful measure for assessing VVA. REJOICE was a 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of a vaginal, muco-adhesive, 17β-estradiol softgel capsule (TX-004HR 4, 10, and 25 μg) in postmenopausal women with VVA and moderate-to-severe dyspareunia. Treatments were self-administered vaginally once per day for 2 weeks, then twice per week for 10 weeks. The vagina was visually examined at baseline and at weeks 2, 6, 8, and 12; changes were evaluated using a 4-item scale for vaginal color, vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal secretions. Significant improvements were observed with all three TX-004HR doses versus placebo in vaginal color (least square mean score changes of -0.96 to -1.06 for TX-004HR doses vs -0.60 for placebo at week 12), epithelial integrity (-0.97 to -1.07 vs -0.60), epithelial surface thickness (-0.94 to -1.03 vs -0.61), and secretions (-1.01 to -1.06 vs -0.64) (P vaginal dryness (P vaginal mucosa of postmenopausal women with VVA and moderate-to-severe dyspareunia were observed with TX-004HR versus placebo, and vaginal mucosa assessment scores correlated with vaginal symptoms of dyspareunia and dryness. Visual vaginal assessment by healthcare professionals is a useful measure for diagnosing VVA and assessing response to treatment.

Qualidade de vida de pacientes com câncer colorretal em uso de suplementação dietética com fungos Agaricus sylvaticus após seis meses de segmento: ensaio clínico aleatorizado e placebo-controlado Quality of life of patients with colorectal cancer on dietary supplementation with Agaricus sylvaticus fungus: after six months of segment: randomized and placebo-controlled clinical trial

Directory of Open Access Journals (Sweden)

Renata Costa Fortes

2007-06-01

Full Text Available INTRODUÇÃO: O câncer gastrointestinal compromete a qualidade de vida devido às alterações fisiológicas, metabólicas e psicológicas. Fungos medicinais podem melhorar a qualidade de vida de pacientes com câncer. OBJETIVO: Avaliar os efeitos da suplementação dietética com fungos Agaricus sylvaticus na qualidade de vida de pacientes com câncer colorretal em fase pós-operatória. METODOLOGIA: Ensaio clínico randomizado, duplo-cego, placebo-controlado, realizado no Hospital de Base do Distrito Federal. Amostra constituída por 56 pacientes (24 homens e 32 mulheres, estádios I, II e III, separados em grupos placebo e Agaricus sylvaticus (30mg/kg/dia, e acompanhados por um período de seis meses. Para avaliar os indicadores da qualidade de vida foram utilizados um formulário-padrão e uma anamnese dirigida-padrão. Os resultados foram analisados de forma qualitativa e descritiva, utilizando os programas Microsoft Excel 2003 e Epi Info 2004. RESULTADOS: Após seis meses de tratamento, observou-se, no grupo Agaricus sylvaticus, aumento da adesão à prática de atividade física, melhora da disposição e do humor, redução das queixas de dores e das alterações do sono como insônia e noites mal dormidas comparado com o grupo placebo. CONCLUSÃO: Os resultados sugerem que a suplementação dietética com Agaricus sylvaticus pode melhorar a qualidade de vida de pacientes no pós-operatório de câncer colorretal.INTRODUCTION: Gastrointestinal cancer jeopardizes the quality of life through physiological, metabolic and psychological alterations. Medicinal fungus may boost the quality of life of patients with cancer. OBJECTIVE: To evaluate the effects of the dietary supplementation with Agaricus sylvaticus fungus in relation to the quality of life in patients with colorectal cancer during post-surgery phase. METHODOLOGY: Randomized, double-blind, placebo-controlled clinical trial carried out at the Federal District Hospital - Brazil, for

Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy : A randomized placebo-controlled study.

Science.gov (United States)

Erhan, Yamac; Erhan, Elvan; Aydede, Hasan; Yumus, Okan; Yentur, Alp

2008-06-01

Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p granisetron, and ondansetron were not significant. Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.

40 CFR 73.20 - Phase II early reduction credits.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Phase II early reduction credits. 73.20 Section 73.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE ALLOWANCE SYSTEM Allowance Allocations § 73.20 Phase II early reduction credits...

Double blind placebo controlled exposure to molds

DEFF Research Database (Denmark)

Meyer, H W; Jensen, K A; Nielsen, K F

2005-01-01

non-significant, and at the same level as after placebo exposure. The developed exposure system based on the Particle-Field and Laboratory Emission Cell (P-FLEC) makes it possible to deliver a precise and highly controlled dose of mold spores from water-damaged building materials, imitating realistic......The objective was to develop an experimental setup for human exposure to mold spores, and to study the clinical effect of this exposure in sensitive subjects who had previously experienced potentially building-related symptoms (BRS) at work. From three water-damaged schools eight employees....... In conclusion this is, to our knowledge, the first study to successfully conduct a human exposure to a highly controlled dose of fungal material aerosolized directly from wet building materials. This short-term exposure to high concentrations of two different molds induced no more reactions than exposure...

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

Science.gov (United States)

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

The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.

Science.gov (United States)

Huttner, Angela; Dayer, Julie-Anne; Yerly, Sabine; Combescure, Christophe; Auderset, Floriane; Desmeules, Jules; Eickmann, Markus; Finckh, Axel; Goncalves, Ana Rita; Hooper, Jay W; Kaya, Gürkan; Krähling, Verena; Kwilas, Steve; Lemaître, Barbara; Matthey, Alain; Silvera, Peter; Becker, Stephan; Fast, Patricia E; Moorthy, Vasee; Kieny, Marie Paule; Kaiser, Laurent; Siegrist, Claire-Anne

2015-10-01

Safe and effective vaccines against Ebola could prevent or control outbreaks. The safe use of replication-competent vaccines requires a careful dose-selection process. We report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based candidate vaccine expressing the Zaire Ebola virus glycoprotein (rVSV-ZEBOV; low-dose vaccinees) compared with 59 volunteers who had received 1 ×10(7) pfu (n=35) or 5 × 10(7) pfu (n=16) of rVSV-ZEBOV (high-dose vaccinees) or placebo (n=8) before a safety-driven study hold. The Geneva rVSV-ZEBOV study, an investigator-initiated phase 1/2, dose-finding, placebo-controlled, double-blind trial conducted at the University Hospitals of Geneva, Switzerland, enrolled non-pregnant, immunocompetent, and otherwise healthy adults aged 18-65 years. Participants from the low-dose group with no plans to deploy to Ebola-aff5cted regions (non-deployable) were randomised 9:1 in a double-blind fashion using randomly permuted blocks of varying sizes to a single injection of 3 × 10(5) pfu or placebo, whereas deployable participants received single-injection 3 × 10(5) pfu open-label. Primary safety and immunogenicity outcomes were the incidence of adverse events within 14 days of vaccination and day-28 antibody titres, respectively, analysed by intention to treat. After viral oligoarthritis was observed in 11 of the first 51 vaccinees (22%) receiving 10(7) or 5 × 10(7) pfu, 56 participants were given a lower dose (3 × 10(5) pfu, n=51) or placebo (n=5) to assess the effect of dose reduction on safety and immunogenicity. This trial is ongoing with a follow-up period of 12 months; all reported results are from interim databases. This study is registered with ClinicalTrials.gov, number NCT02287480. Between Jan 5 and Jan 26, 2015, 43 non-deployable participants received low-dose rVSV-ZEBOV (3 × 10(5) pfu) or placebo in a

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

Directory of Open Access Journals (Sweden)

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.

Recombinant streptokinase suppositories in the treatment of acute haemorrhoidal disease. Multicentre randomized double-blind placebo-controlled trial (THERESA-2).

Science.gov (United States)

Hernández-Bernal, F; Valenzuela-Silva, C M; Quintero-Tabío, L; Castellanos-Sierra, G; Monterrey-Cao, D; Aguilera-Barreto, A; López-Saura, P

2013-11-01

A four-arm multicentre randomized double-blind placebo-controlled trial was undertaken to assess the effect and safety of suppositories containing recombinant streptokinase (rSK) at two dose levels (100,000 IU and 200,000 IU) with sodium salicylate (SS) compared with placebo and SS for the treatment of acute haemorrhoidal disease. Patients with acute symptoms of haemorrhoids were randomized to four treatment groups: (I) placebo, (II) SS, (III) SS + rSK 100,000 IU and (IV) SS + rSK 200,000 IU per suppository. Inpatient treatment was by four suppositories given every 6 h to discharge at 24 h. Evaluations were made at the time of discharge (24 h) and at 3, 5 and 20 days later. The main end-point was the degree of relief of pain, oedema and reduction in the size of the lesion by 90% on day 5. Adverse events and the occurrence of anti-SK antibodies were also determined. Eighty patients were included. Respective response rates in the four groups were 16%, 30%, 25% and 52%. In the last group there was a significant difference (36.8%) compared with control (95% CI 7.0-58.4%). The time to response was significantly shorter (median 5 days) in the 200,000 IU rSK group with respect to the others. There were no adverse events attributable to the treatment. No increase in anti-SK antibodies was detected 20 days after treatment. Suppositories with 200,000 IU rSK showed a significant improvement in symptoms of acute haemorrhoids, with an adequate safety profile. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

The Gerda Phase II detector assembly

Energy Technology Data Exchange (ETDEWEB)

Bode, Tobias; Schoenert, Stefan [Physik-Department E15, Technische Universitaet Muenchen (Germany); Schwingenheuer, Bernhard [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Collaboration: GERDA-Collaboration

2013-07-01

Phase II of the Gerda (Germanium Detector Array) experiment will continue the search for the neutrinoless double beta decay (0νββ) of {sup 76}Ge. Prerequisites for Phase II are an increased target mass and a reduced background index of < 10 {sup -3} cts/(keV.kg.yr). Major hardware upgrades to achieve these requirements are scheduled for 2013. They include the deployment of a new radio pure low mass detector assembly. The structural properties of available radio-pure materials and reduction of mass necessitate a change of the electrical contacting used to bias and read-out the detectors. The detector assembly design and the favored contacting solution are presented.

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

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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

Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.

Science.gov (United States)

Shaibani, Aziz I; Pope, Laura E; Thisted, Ronald; Hepner, Adrian

2012-02-01

To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain. In a 13-week, phase 3, randomized controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain for ≥3 months received double-blind placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. Efficacy measures included four pain rating scales applied daily using patient diaries, and another two applied at five clinic visits. On all six scales, DMQ 45/30 mg was significantly superior to placebo, including the primary efficacy analysis, which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale (P < 0.0001). Sensitivity analyses gave consistent results. Efficacy vs placebo was also seen for diary ratings of present pain intensity, and pain interference with sleep and with activities (all P < 0.0001). Among clinic visit assessments, DMQ 45/30 mg demonstrated greater leg pain relief (P = 0.0002) and greater reduction of leg pain intensity (P = 0.0286) vs placebo. The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo. Adverse events were mostly mild or moderate and of expected types. Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo. Throughout a 13-week trial, DMQ was effective, with an acceptable safety profile, for treatment of DPN pain. Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy. Wiley Periodicals, Inc.

Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study.

Science.gov (United States)

Kanzaki, Noriyuki; Ono, Yoshiko; Shibata, Hiroshi; Moritani, Toshio

2015-01-01

The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren-Lawrence (K-L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, Pknee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions.

Placebo can enhance creativity.

Directory of Open Access Journals (Sweden)

Liron Rozenkrantz

Full Text Available The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition.Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45, and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45. Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG, and a randomly chosen subset (n = 57 also completed two manual standardized creativity tests, the alternate uses test (AUT and the Torrance test (TTCT. In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency.The placebo group showed higher originality than the control group both in the CFG (p<0.04, effect size = 0.5 and in the AUT (p<0.05, effect size = 0.4, but not in the Torrance test. The placebo group also found more shapes outside of the standard categories found by a set of 100 CFG players in a previous study, a feature termed out-of-the-boxness (p<0.01, effect size = 0.6.The findings indicate that placebo can enhance the originality aspect of creativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which

PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

Directory of Open Access Journals (Sweden)

Day Richard O

2010-07-01

Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial.

Science.gov (United States)

Thaçi, Diamant; Simpson, Eric L; Beck, Lisa A; Bieber, Thomas; Blauvelt, Andrew; Papp, Kim; Soong, Weily; Worm, Margitta; Szepietowski, Jacek C; Sofen, Howard; Kawashima, Makoto; Wu, Richard; Weinstein, Steven P; Graham, Neil M H; Pirozzi, Gianluca; Teper, Ariel; Sutherland, E Rand; Mastey, Vera; Stahl, Neil; Yancopoulos, George D; Ardeleanu, Marius

2016-01-02

Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments. In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988. Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more

Importance of placebo effect in cough clinical trials.

Science.gov (United States)

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.

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...

Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial

NARCIS (Netherlands)

Beuers, U.; Spengler, U.; Kruis, W.; AYDEMIR, U.; WIEBECKE, B.; HELDWEIN, W.; WEINZIERL, M.; Pape, G. R.; Sauerbruch, T.; Paumgartner, G.

1992-01-01

The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver

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

NARCIS (Netherlands)

Westenberg, HGM; Stein, DJ; Yang, HC; Li, D; Barbato, LM

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

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

Science.gov (United States)

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-07-17

Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © 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.

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

Science.gov (United States)

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.

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 idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial.

Science.gov (United States)

Buyse, Gunnar M; Voit, Thomas; Schara, Ulrike; Straathof, Chiara S M; D'Angelo, M Grazia; Bernert, Günther; Cuisset, Jean-Marie; Finkel, Richard S; Goemans, Nathalie; McDonald, Craig M; Rummey, Christian; Meier, Thomas

2015-05-02

Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids. In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10-18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks. Study personnel and patients were masked to treatment assignment. The primary endpoint was change in peak expiratory flow (PEF) as percentage predicted (PEF%p) from baseline to week 52, measured with spirometry. Analysis was by intention to treat (ITT) and a modified ITT (mITT), which was prospectively defined to exclude patients with at least 20% difference in the yearly change in PEF%p, measured with hospital-based and weekly home-based spirometry. This study is registered with ClinicalTrials.gov, number NCT01027884. 31 patients in the idebenone group and 33 in the placebo group comprised the ITT population, and 30 and 27 comprised the mITT population. Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT (-3·05%p [95% CI -7·08 to 0·97], p=0·134, vs placebo -9·01%p [-13·18 to -4·84], p=0·0001; difference 5·96%p [0·16 to 11·76], p=0·044) and ITT populations (-2·57%p [-6·68 to 1·54], p=0·215, vs -8·84%p [-12·73 to -4·95], pmuscular dystrophy. Santhera Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial.

Science.gov (United States)

Fan, Dazhi; Wu, Shuzhen; Ye, Shaoxin; Wang, Wen; Guo, Xiaoling; Liu, Zhengping

2017-11-01

Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche. This phase II clinical trial is a single-center, prospective, randomized, double-blind, placebo-controlled with 2 arms. One hundred twenty primiparous participants will be randomly (1:1 ratio) assigned to receive direct intramuscular injection of MSCs (a dose of 1*10 cells in 1 mL of 0.9% saline) (MSCs group) or an identical-appearing 1 mL of 0.9% saline (placebo-controlled group) near the uterine incision. The primary outcome of this trial is to evaluate the proportion of participants at 6 months who is found uterine niche in the uterus by transvaginal utrasonography. Adverse events will be documented in a case report form. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. This trial is the first investigation of the potential for therapeutic use of MSCs for the management of uterine niche after cesarean delivery. This protocol will help to determine the efficacy and safety of MSCs treatment in uterine niche and bridge the gap with regards to the current preclinical and clinical evidence. NCT02968459 (Clinical Trials.gov: http://clinicaltrials.gov/).

Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status.

Science.gov (United States)

Goss, Glenwood; Ferry, David; Wierzbicki, Rafal; Laurie, Scott A; Thompson, Joyce; Biesma, Bonne; Hirsch, Fred R; Varella-Garcia, Marileila; Duffield, Emma; Ataman, Ozlem U; Zarenda, Marc; Armour, Alison A

2009-05-01

To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status. NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored. Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred. There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors.

Exxon nuclear power distribution control for pressurized water reactors: Phase II

International Nuclear Information System (INIS)

Holm, J.S.; Burnside, R.J.

1978-01-01

The power distribution control procedure, denoted PDC-II, described in this report enables nuclear plants to manage core power distributions such that Technical Specification Limits on F/sub Q//sup T/ are not violated during normal operation and limits on MDNBR are not violated during steady-state, load-follow, and anticipated transients. The PDC-II data base described provides the means for predicting the maximum F/sub Q//sup T/(z) distribution anticipated during operation under the PDC-II procedure taking into account the incore measured equilibrium power distribution data for the reactor in question. A comparison of this distribution with the Technical Specification limit curve determines whether the Technical Specification limit can be protected by PDC-II procedure. If such protection can be confirmed for a given operating cycle interval, APDMS monitoring is not necessary over this interval and the excore monitored constant axial offset limits will protect the Technical Specification F/sub Q//sup T/ limits. This document describes the maximum possible variation in F/sub Q//sup T/(z) which can occur during operation when following the PDC-II procedures. This bounding variation in F/sub Q//sup T/(z) is referred to as V(z). This V(z) distribution represents the maximun variation in F/sub Q//sup T/(z) when the axial offset is maintained within the range defined in this report [+- 5% at full power condition

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

Directory of Open Access Journals (Sweden)

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.

HPC Benchmark Suite NMx, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — In the phase II effort, Intelligent Automation Inc., (IAI) and University of Central Florida (UCF) propose to develop a comprehensive numerical test suite for...

Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study

NARCIS (Netherlands)

Chlibek, Roman; Smetana, Jan; Pauksens, Karlis; Rombo, Lars; van den Hoek, J. Anneke R.; Richardus, Jan H.; Plassmann, Georg; Schwarz, Tino F.; Ledent, Edouard; Heineman, Thomas C.

2014-01-01

This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system AS01B. In this phase II, single-blind, randomized, controlled study,

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

Science.gov (United States)

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).

Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

Directory of Open Access Journals (Sweden)

Øystein Fluge

Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

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.

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

Science.gov (United States)

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

Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

Science.gov (United States)

Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

2015-01-01

Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

Horonobe Underground Research Laboratory project. Synthesis of phase II (construction phase) investigations to a depth of 350 m

International Nuclear Information System (INIS)

Sato, Toshinori; Sasamoto, Hiroshi; Ishii, Eiichi; Matsuoka, Toshiyuki; Hayano, Akira; Miyakawa, Kazuya; Fujita, Tomoo; Tanai, Kenji; Nakayama, Masashi; Takeda, Masaki; Yokota, Hideharu; Aoyagi, Kazuhei; Ohno, Hirokazu; Shigeta, Naotaka; Hanamuro, Takahiro; Ito, Hiroaki

2017-03-01

The Horonobe Underground Research Laboratory (URL) Project is being pursued by the Japan Atomic Energy Agency (JAEA) to enhance the reliability of relevant disposal technologies through investigations of the deep geological environment within the host sedimentary formations at Horonobe, northern Hokkaido. The project consists of two major research areas, 'Geoscientific Research' and 'R and D on Geological Disposal', and proceeds in three overlapping phases, 'Phase I: Surface-based investigation', 'Phase II: Construction' and 'Phase III: Operation', over a period of 20 years. This report summarizes the results of the Phase II investigations carried out from April 2005 to June 2014 to a depth of 350 m. Integration of work from different disciplines into a 'geosynthesis' ensures that the Phase II goals have been successfully achieved and identifies key issues that need to be addressed in the Phase II investigations. Efforts are made to summarize as many lessons learnt from the Phase II investigations and other technical achievements as possible to form a 'knowledge base' that will reinforce the technical basis for both implementation and the formulation of safety regulations. (author)

Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study.

Science.gov (United States)

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.

Crew Cerebral Oxygen Monitor, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — This Phase II SBIR proposal is aimed at developing a non-invasive, optical method for monitoring crew member state of awareness in operational environments. All...

MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

Science.gov (United States)

Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

2017-05-01

This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P 0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

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).

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

Directory of Open Access Journals (Sweden)

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.

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.

Phase II Final Report

Energy Technology Data Exchange (ETDEWEB)

Schuknecht, Nate [Project Manager; White, David [Principle Investigator; Hoste, Graeme [Research Engineer

2014-09-11

The SkyTrough DSP will advance the state-of-the-art in parabolic troughs for utility applications, with a larger aperture, higher operating temperature, and lower cost. The goal of this project was to develop a parabolic trough collector that enables solar electricity generation in the 2020 marketplace for a 216MWe nameplate baseload power plant. This plant requires an LCOE of 9¢/kWhe, given a capacity factor of 75%, a fossil fuel limit of 15%, a fossil fuel cost of $6.75/MMBtu, $25.00/kWht thermal storage cost, and a domestic installation corresponding to Daggett, CA. The result of our optimization was a trough design of larger aperture and operating temperature than has been fielded in large, utility scale parabolic trough applications: 7.6m width x 150m SCA length (1,118m2 aperture), with four 90mm diameter × 4.7m receivers per mirror module and an operating temperature of 500°C. The results from physical modeling in the System Advisory Model indicate that, for a capacity factor of 75%: The LCOE will be 8.87¢/kWhe. SkyFuel examined the design of almost every parabolic trough component from a perspective of load and performance at aperture areas from 500 to 2,900m2. Aperture-dependent design was combined with fixed quotations for similar parts from the commercialized SkyTrough product, and established an installed cost of $130/m2 in 2020. This project was conducted in two phases. Phase I was a preliminary design, culminating in an optimum trough size and further improvement of an advanced polymeric reflective material. This phase was completed in October of 2011. Phase II has been the detailed engineering design and component testing, which culminated in the fabrication and testing of a single mirror module. Phase II is complete, and this document presents a summary of the comprehensive work.

Improved Metal-Polymeric Laminate Radiation Shielding, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — In this proposed Phase II program, builds on the phase I feaibility where a multifunctional lightweight radiation shield composite was developed and fabricated. This...

Performance of BEGe detectors for GERDA Phase II

Energy Technology Data Exchange (ETDEWEB)

Lazzaro, Andrea [Physik-Department E15, Technische Universitaet Muenchen (Germany); Collaboration: GERDA-Collaboration

2015-07-01

After the end of the data-taking for GERDA Phase I, the apparatus has been upgraded to fulfill the requirements of the second phase. Phase II sensitivity will be driven by 30 custom made BEGe detectors. This detectors are now available and can be operated in phaseII configuration in the GERDA cryostat together with the liquid argon scintillation veto. The performances of BEGe detectors in liquid argon are presented in this talk. Besides the spectroscopy capability, the focus will be placed on the expectations in terms of background rejection via pulse shape discrimination (PSD). In particular the main goal the BEGe's pulse shape analysis is to discriminate surface events produced by beta emitters (e.g. {sup 42}K) present in the liquid Ar.

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

Science.gov (United States)

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.

A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings.

Science.gov (United States)

Mix, Joseph A; Crews, W David

2002-08-01

There appears to be an absence of large-scaled clinical trials that have examined the efficacy of Ginkgo biloba extract on the neuropsychological functioning of cognitively intact older adults. The importance of such clinical research appears paramount in light of the plethora of products containing Ginkgo biloba that are currently being widely marketed to predominantly cognitively intact adults with claims of enhanced cognitive performances. The purpose of this research was to conduct the first known, large-scaled clinical trial of the efficacy of Ginkgo biloba extract (EGb 761) on the neuropsychological functioning of cognitively intact older adults. Two hundred and sixty-two community-dwelling volunteers (both male and female) 60 years of age and older, who reported no history of dementia or significant neurocognitive impairments and obtained Mini-Mental State Examination total scores of at least 26, were examined via a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group, clinical trial. Participants were randomly assigned to receive either Ginkgo biloba extract EGb 761(n = 131; 180 mg/day) or placebo (n = 131) for 6 weeks. Efficacy measures consisted of participants' raw change in performance scores from pretreatment baseline to those obtained just prior to termination of treatment on the following standardized neuropsychological measures: Selective Reminding Test (SRT), Wechsler Adult Intelligence Scale-III Block Design (WAIS-III BD) and Digit Symbol-Coding (WAIS-III DS) subtests, and the Wechsler Memory Scale-III Faces I (WMS-III FI) and Faces II (WMS-III FII) subtests. A subjective Follow-up Self-report Questionnaire was also administered to participants just prior to termination of the treatment phase. Analyses of covariance indicated that cognitively intact participants who received 180 mg of EGb 761 daily for 6 weeks exhibited significantly more improvement on SRT tasks involving delayed (30 min) free recall (p visual material

Randomized Phase II Study of Gefitinib Compared With Placebo in Chemotherapy-Naive Patients With Advanced Non–Small-Cell Lung Cancer and Poor Performance Status

Science.gov (United States)

Goss, Glenwood; Ferry, David; Wierzbicki, Rafal; Laurie, Scott A.; Thompson, Joyce; Biesma, Bonne; Hirsch, Fred R.; Varella-Garcia, Marileila; Duffield, Emma; Ataman, Ozlem U.; Zarenda, Marc; Armour, Alison A.

2009-01-01

Purpose To compare gefitinib with placebo in chemotherapy naïve patients with advanced non–small-cell lung cancer (NSCLC) and poor performance status. Patients and Methods NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored. Results Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred. Conclusion There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors. PMID:19289623

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.

Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Ludvik, Bernhard; Frías, Juan P; Tinahones, Francisco J; Wainstein, Julio; Jiang, Honghua; Robertson, Kenneth E; García-Pérez, Luis-Emilio; Woodward, D Bradley; Milicevic, Zvonko

2018-05-01

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA. Eligible adult patients (≥18 years) with inadequately controlled type 2 diabetes (HbA 1c concentration ≥7·0% [53 mmol/mol] and ≤9·5% [80 mmol/mol]), a BMI of 45 kg/m 2 or less, and taking stable doses (>3 months) of an SGLT2 inhibitor (with or without metformin) were randomly assigned (1:1:1) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg, dulaglutide 0·75 mg, or placebo once per week for 24 weeks. Patients and investigators were masked to dulaglutide and placebo assignment, and those assessing outcomes were masked to study drug assignment. The primary objective was to test for the superiority of dulaglutide (1·5 mg or 0·75 mg) versus placebo for change in HbA 1c concentration from baseline at 24 weeks. All analyses were done in the intention-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02597049. Between Dec 7, 2015, and Feb 3, 2017, 424 patients were randomly assigned to dulaglutide 1·5 mg (n=142), dulaglutide 0·75 mg (n=142), and placebo (n=140). One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug. The reduction in HbA 1c concentration at 24 weeks was larger

Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study.

Science.gov (United States)

Papakostas, George I; Fava, Maurizio; Baer, Lee; Swee, Michaela B; Jaeger, Adrienne; Bobo, William V; Shelton, Richard C

2015-12-01

The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.

Innovation in the Sky, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — This Phase II proposal presents a scope of work to develop reliable Sense and Avoid for BVLOS Unmanned Aerial Vehicle [UAV] operations. We first analyze a) the...

Kursk Operation Simulation and Validation Exercise - Phase II (KOSAVE II)

National Research Council Canada - National Science Library

Bauman, Walter

1998-01-01

... (KOSAVE) Study (KOSAVE II) documents, in this report a statistical record of the Kursk battle, as represented in the KDB, for use as both a standalone descriptive record for historians, and as a baseline for a subsequent Phase...

A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome.

Directory of Open Access Journals (Sweden)

David R Strayer

Full Text Available BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C(12U, in patients with debilitating CFS/ME. METHODS AND FINDINGS: A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET. Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS, Activities of Daily Living (ADL, and Vitality Score (SF 36. Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047 from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022. The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048. Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04. Rintatolimod at 400 mg twice weekly was generally well-tolerated. CONCLUSIONS/SIGNIFICANCE: Rintatolimod produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00215800.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Advanced Communication and Control for Distributed Energy Resource Integration: Phase 2 Scientific Report

Energy Technology Data Exchange (ETDEWEB)

BPL Global

2008-09-30

The objective of this research project is to demonstrate sensing, communication, information and control technologies to achieve a seamless integration of multivendor distributed energy resource (DER) units at aggregation levels that meet individual user requirements for facility operations (residential, commercial, industrial, manufacturing, etc.) and further serve as resource options for electric and natural gas utilities. The fully demonstrated DER aggregation system with embodiment of communication and control technologies will lead to real-time, interactive, customer-managed service networks to achieve greater customer value. Work on this Advanced Communication and Control Project (ACCP) consists of a two-phase approach for an integrated demonstration of communication and control technologies to achieve a seamless integration of DER units to reach progressive levels of aggregated power output. Phase I involved design and proof-of-design, and Phase II involves real-world demonstration of the Phase I design architecture. The scope of work for Phase II of this ACCP involves demonstrating the Phase I design architecture in large scale real-world settings while integrating with the operations of one or more electricity supplier feeder lines. The communication and control architectures for integrated demonstration shall encompass combinations of software and hardware components, including: sensors, data acquisition and communication systems, remote monitoring systems, metering (interval revenue, real-time), local and wide area networks, Web-based systems, smart controls, energy management/information systems with control and automation of building energy loads, and demand-response management with integration of real-time market pricing. For Phase II, BPL Global shall demonstrate the Phase I design for integrating and controlling the operation of more than 10 DER units, dispersed at various locations in one or more Independent System Operator (ISO) Control Areas, at

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...

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults.

Directory of Open Access Journals (Sweden)

Juliet Mpendo

Full Text Available Strategies to enhance the immunogenicity of DNA vaccines in humans include i co-administration of molecular adjuvants, ii intramuscular administration followed by in vivo electroporation (IM/EP and/or iii boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG plasmid DNA (pDNA vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12 (GENEVAX IL-12 given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs were reported. T cell and antibody response rates after HIVMAG (x3 prime-Ad35 (x1 boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ ELISPOT responses was highest after HIVMAG (x3 without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3 prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.ClinicalTrials.gov NCT01496989.

Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

International Nuclear Information System (INIS)

Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea; Zapf, Antonia; Pradier, Olivier; Schmidberger, Heinz

2009-01-01

Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

Energy Technology Data Exchange (ETDEWEB)

Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea [Dept. of Radiotherapy and Radiooncology, Univ. of Goettingen (Germany); Zapf, Antonia [Dept. of Medical Statistics, Univ. of Goettingen (Germany); Pradier, Olivier [Dept. of Radiotherapy and Radiooncology, Univ. of Brest (France); Schmidberger, Heinz [Dept. of Radiotherapy and Radiooncology, Univ. of Mainz (Germany)

2009-09-15

Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Bussel, James B; Provan, Drew; Shamsi, Tahir; Cheng, Gregory; Psaila, Bethan; Kovaleva, Lidia; Salama, Abdulgabar; Jenkins, Julian M; Roychowdhury, Debasish; Mayer, Bhabita; Stone, Nicole; Arning, Michael

2009-02-21

Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; ptime during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.

Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study

NARCIS (Netherlands)

Nosten, F.; ter Kuile, F.; Maelankiri, L.; Chongsuphajaisiddhi, T.; Nopdonrattakoon, L.; Tangkitchot, S.; Boudreau, E.; Bunnag, D.; White, N. J.

1994-01-01

A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border. Mefloquine gave > or = 86% (95% confidence interval [CI],

Nano-Phase Powder Based Exothermic Braze Repair Technology For RCC Materials, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The Phase II project will advance innovative, cost effective and reliable nano-phase exothermic RCC joining processes (ExoBrazeTM) in order to be able to reinforce...

A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer

International Nuclear Information System (INIS)

Warde, Padraig; O'Sullivan, Brian; Aslanidis, Julie; Kroll, Barbaranne; Lockwood, Gina; Waldron, John; Payne, David; Bayley, Andrew; Ringash, Jolie; Kim, John; Liu, F.-F.; Maxymiw, Walter; Sprague, Shelley; Cummings, Bernard J.

2002-01-01

Purpose: To test the hypothesis that the use of oral pilocarpine during and after radiotherapy (RT) for head-and-neck cancer would reduce the symptoms of post-RT xerostomia. Methods and Materials: One hundred thirty patients were randomized in a double-blind method to receive either pilocarpine (5-mg tablets) or placebo three times daily starting on Day 1 of RT and continuing for 1 month after treatment. The eligibility criteria included a planned dose of >50 Gy as radical or postoperative RT for head-and-neck cancer, with at least 50% of both parotid glands included in the treatment fields. The primary outcome measure was the severity of xerostomia as assessed by a patient-completed linear analog scale 3 months after RT. Secondary outcome measures included quality of life during therapy (as assessed by the McMaster University Head-and-Neck Questionnaire) and severity of mucositis during RT (as assessed using Radiation Therapy Oncology Group scales). Results: No difference was observed between the pilocarpine-treated patients and the placebo group in the severity of xerostomia score as assessed by linear analog scale at baseline and 1, 3, and 6 months after treatment (repeated measures analysis, p=0.92). No difference was apparent in the severity of mucositis during RT; 56.3% of patients receiving pilocarpine had Grade III/IV mucositis compared with 50.8% treated with placebo. No difference in quality of life was noted between the treatment groups during or after RT. The questionnaire score at 3 months after RT was 5.0 (SD 1.0). in the pilocarpine group and 4.9 (SD 0.9) in the placebo group. Conclusion: We were unable to detect a beneficial effect of pilocarpine on RT-induced xerostomia when administered during RT for head-and-neck cancer

Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial.

Science.gov (United States)

Poewe, Werner; Seppi, Klaus; Fitzer-Attas, Cheryl J; Wenning, Gregor K; Gilman, Sid; Low, Phillip A; Giladi, Nir; Barone, Paolo; Sampaio, Cristina; Eyal, Eli; Rascol, Olivier

2015-02-01

Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic

Mood Predicts Response to Placebo CPAP

Directory of Open Access Journals (Sweden)

Carl J. Stepnowsky

2012-01-01

Full Text Available Study Objectives. Continuous positive airway pressure (CPAP therapy is efficacious for treating obstructive sleep apnea (OSA, but recent studies with placebo CPAP (CPAP administered at subtherapeutic pressure have revealed nonspecific (or placebo responses to CPAP treatment. This study examined baseline psychological factors associated with beneficial effects from placebo CPAP treatment. Participants. Twenty-five participants were studied with polysomnography at baseline and after treatment with placebo CPAP. Design. Participants were randomized to either CPAP treatment or placebo CPAP. Baseline mood was assessed with the Profile of Mood States (POMS. Total mood disturbance (POMS-Total was obtained by summing the six POMS subscale scores, with Vigor weighted negatively. The dependent variable was changed in apnea-hypopnea index (ΔAHI, calculated by subtracting pre- from post-CPAP AHI. Negative values implied improvement. Hierarchical regression analysis was performed, with pre-CPAP AHI added as a covariate to control for baseline OSA severity. Results. Baseline emotional distress predicted the drop in AHI in response to placebo CPAP. Highly distressed patients showed greater placebo response, with a 34% drop (i.e., improvement in AHI. Conclusion. These findings underscore the importance of placebo-controlled studies of CPAP treatment. Whereas such trials are routinely included in drug trials, this paper argues for their importance even in mechanical-oriented sleep interventions.

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

Science.gov (United States)

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.

Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain – a randomized, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Blahova Z

2016-12-01

Full Text Available Zuzana Blahova,1 Janina Claudia Holm,1 Thomas Weiser,2 Erika Richter,2 Matthias Trampisch,2 Elena Akarachkova3 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background/objective: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC of nonivamide (a capsaicinoid and nicoboxil (a nicotinic acid ester cream in the treatment of acute nonspecific low back pain.Materials and methods: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1.08%/nonivamide 0.17% (Finalgon® cream in treatment of acute nonspecific low back pain with the endpoints: pain intensity (PI difference between pre-dose baseline and 8 hours after first application and the end of treatment, mobility score, and efficacy score.Results: Patients (n=138, 21–65 years of age, were treated for up to 4 days with FDC or placebo cream. Mean baseline PI was 6.8 on a 0–10 point numerical rating scale. After 8 hours, pain was more reduced with the FDC than with placebo (adjusted means: 2.824 vs. 0.975 points; p<0.0001. On the last treatment day, mean pain reduction by the FDC was stronger than with placebo (adjusted means: 5.132 vs. 2.174 points; p<0.0001. Mobility on Day 1 was in favor of the FDC when compared to placebo (odds ratio [95% confidence interval {CI}]: 7.200 [3.609, 14.363], p<0.0001. At the end of treatment, patients treated with the FDC rated efficacy significantly higher than placebo (odds ratio [95% CI]: 11.370 [5.342, 24.199], p<0.0001. Both treatments were tolerated well. No serious adverse events were reported.Conclusion: Nicoboxil

Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia.

Science.gov (United States)

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

Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer.

Science.gov (United States)

Michaelson, M Dror; Oudard, Stephane; Ou, Yen-Chuan; Sengeløv, Lisa; Saad, Fred; Houede, Nadine; Ostler, Peter; Stenzl, Arnulf; Daugaard, Gedske; Jones, Robert; Laestadius, Fredrik; Ullèn, Anders; Bahl, Amit; Castellano, Daniel; Gschwend, Juergen; Maurina, Tristan; Chow Maneval, Edna; Wang, Shaw-Ling; Lechuga, Maria Jose; Paolini, Jolanda; Chen, Isan

2014-01-10

We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%). The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes.

Science.gov (United States)

Lundkvist, Per; Sjöström, C David; Amini, Sam; Pereira, Maria J; Johnsson, Eva; Eriksson, Jan W

2017-01-01

To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes. In this single-centre, double-blind trial, we randomized 50 obese adults without diabetes (aged 18-70 years; body mass index 30-45 kg/m 2 ) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately. Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was -4.13 kg (95% confidence interval -6.44, -1.81; P prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effects of Panax ginseng extract in patients with fibromyalgia: a 12-week, randomized, double-blind, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Alessandra S. Braz

2013-03-01

Full Text Available The purpose of the study was to evaluate the efficacy of an extract of Panax ginseng in patients with fibromyalgia. A randomized, double-blind, controlled clinical trial was carried out over 12 weeks to compare the effects of P. ginseng (100 mg/d with amitriptyline (25 mg/d and placebo in 38 patients with fibromyalgia: 13 in Group I (amitriptyline, 13 in Group II (placebo, and 12 in Group III (P. ginseng. Ratings on the Visual Analogue Scale (VAS revealed a reduction in pain in the P. ginseng group (p < .0001, an improvement in fatigue (p < .0001 and an improvement in sleep (p < .001, with respect to baseline characteristics, but there were no differences between the three groups. With respect to anxiety, improvements occurred in the P. ginseng group compared to baseline (p < .0001; however, amitriptyline treatment resulted in significantly greater improvements (p < .05. P. ginseng reduced the number of tender points and improved patients' quality of life (using the Fibromyalgia Impact Questionnaire - FIQ; however, there were no differences between groups. The beneficial effects experienced by patients for all parameters suggest a need for further studies to be performed on the tolerability and efficacy of this phytotherapic as a complementary therapy for fibromyalgia.

First results of GERDA Phase II and consistency with background models

Science.gov (United States)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode1, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-01-01

The GERDA (GERmanium Detector Array) is an experiment for the search of neutrinoless double beta decay (0νββ) in 76Ge, located at Laboratori Nazionali del Gran Sasso of INFN (Italy). GERDA operates bare high purity germanium detectors submersed in liquid Argon (LAr). Phase II of data-taking started in Dec 2015 and is currently ongoing. In Phase II 35 kg of germanium detectors enriched in 76Ge including thirty newly produced Broad Energy Germanium (BEGe) detectors is operating to reach an exposure of 100 kg·yr within about 3 years data taking. The design goal of Phase II is to reduce the background by one order of magnitude to get the sensitivity for T1/20ν = O≤ft( {{{10}26}} \\right){{ yr}}. To achieve the necessary background reduction, the setup was complemented with LAr veto. Analysis of the background spectrum of Phase II demonstrates consistency with the background models. Furthermore 226Ra and 232Th contamination levels consistent with screening results. In the first Phase II data release we found no hint for a 0νββ decay signal and place a limit of this process T1/20ν > 5.3 \\cdot {1025} yr (90% C.L., sensitivity 4.0·1025 yr). First results of GERDA Phase II will be presented.

Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

Science.gov (United States)

Heymach, John V; Paz-Ares, Luis; De Braud, Filippo; Sebastian, Martin; Stewart, David J; Eberhardt, Wilfried E E; Ranade, Anantbhushan A; Cohen, Graham; Trigo, Jose Manuel; Sandler, Alan B; Bonomi, Philip D; Herbst, Roy S; Krebs, Annetta D; Vasselli, James; Johnson, Bruce E

2008-11-20

Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.

Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

DEFF Research Database (Denmark)

Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

2002-01-01

In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

The role of ultrasound in controlling the liquid-liquid phase separation and nucleation of vanillin polymorphs I and II

Science.gov (United States)

Parimaladevi, P.; Supriya, S.; Srinivasan, K.

2018-02-01

The influence of ultrasound on liquid-liquid phase separation (LLPS) and polymorphism of vanillin in aqueous solution has been investigated for the first time by varying the ultrasonic parameters such as power, pulse rate and insonation time at ambient condition. Results reveal that the application of ultrasound controls the impact of LLPS and accelerates the nucleation of vanillin within a short period at lower levels of ultrasonic process parameters, and also enhances the quality of the nucleated crystals. Moreover, the application of ultrasound induces the nucleation of rare and metastable polymorph of vanillin Form II in aqueous solution. But, at higher levels of power, pulse rate and insonation time, the rate of LLPS is found increased and the quality of the crystals becomes deteriorated. Morphology of the nucleated polymorphs were identified through optical microscopy and confirmed by optical goniometry. The internal structure and thermal stability of the grown stable Form I and metastable Form II of vanillin were confirmed through powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses. Further, results suggest that the ultrasound has profound effect in controlling the LLPS and nucleation of vanillin polymorphs in aqueous solution.

Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

Science.gov (United States)

Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

2007-07-01

Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

Operator interface for the PEP-II low level RF control system

International Nuclear Information System (INIS)

Allison, S.; Claus, R.

1997-05-01

This paper focuses on the operational aspects of the low level RF control system being built for the PEP-II storage rings at SLAC. Subsystems requiring major operational considerations include displays for monitor and control from UNIX workstations, slow feedback loops and control sequences residing on microprocessors, and various client applications in the existing SLAC Linear Collider (SLC) control system. Since commissioning of PEP-II RF is currently in-progress, only those parts of the control system used during this phase are discussed in detail. Based on past experience with the SLC control system, it is expected that effort expended during commissioning on a solid user interface will result in smoother transition to full reliable 24-hour-a-day operation

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

Science.gov (United States)

Blauvelt, Andrew; de Bruin-Weller, Marjolein; Gooderham, Melinda; Cather, Jennifer C; Weisman, Jamie; Pariser, David; Simpson, Eric L; Papp, Kim A; Hong, H Chih-Ho; Rubel, Diana; Foley, Peter; Prens, Errol; Griffiths, Christopher E M; Etoh, Takafumi; Pinto, Pedro Herranz; Pujol, Ramon M; Szepietowski, Jacek C; Ettler, Karel; Kemény, Lajos; Zhu, Xiaoping; Akinlade, Bolanle; Hultsch, Thomas; Mastey, Vera; Gadkari, Abhijit; Eckert, Laurent; Amin, Nikhil; Graham, Neil M H; Pirozzi, Gianluca; Stahl, Neil; Yancopoulos, George D; Shumel, Brad

2017-06-10

Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov, NCT02260986. Between Oct 3, 2014

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

DEFF Research Database (Denmark)

Ripa, RS; Jorgensen, E; Wang, Y

2006-01-01

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of......: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group...

The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.

Science.gov (United States)

Ghali, Jalal K; Orlandi, Cesare; Abraham, William T

2012-06-01

Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload. This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated. NCT01055912.

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

Science.gov (United States)

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

[Placebo effect in Parkinson's disease].

Science.gov (United States)

Miwa, Hideto

2007-02-01

"Placebo" is Latin for "I shall please". The placebo effect has been widely documented by randomized placebo-controlled drug studies. One of the best examples of placebo effectiveness is that have been shown in clinical trials of anti-parkinsonian drugs. The placebo effect is observable not only in drug trials but also with deep brain stimulation. Recent advances in research on the placebo effect in Parkinson's disease (PD) have suggested that motor symptoms of PD can be essentially improved by placebo. A recent study using positron emission tomography (PET) with raclopride demonstrated that release of endogeneous dopamine in the dorsal striatum occurs in placebo-responsive patients with PD. This suggests that placebo-induced expectation of clinical improvement may activate endogenous dopamine in the striatum, and that placebo effectiveness is thus achieved by endogenous dopamine supplementation. Indeed, decreased neuronal activities in the subthalamic nucleus (STN), that were recorded during surgery to implant deep brain stimulation electrodes, correlated well with placebo-induced clinical improvement in patients with PD. Although the detailed pathophysiological mechanism underlying the placebo effects remains uncertain, theoretically, the placebo effect has generally been explained by two different mechanisms: one is conditioning theory (pavlovian conditioning), and the other is cognitive theory (expectation of clinical improvement). Although both mechanisms may contribute to placebo effects, the placebo effect in PD may be attributed more to cognitive mechanisms such as expectation of improvement, because the placebo effect can be obtained in de novo PD patients. There have been accumulating findings that suggest a functional relationship between dopamine and the expectation of clinical improvement (reward). Further basic studies are required to clarify the complex link between dopamine and the reward system, but such findings will contribute to a better

Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study.

Science.gov (United States)

Heppner, D Gray; Kemp, Tracy L; Martin, Brian K; Ramsey, William J; Nichols, Richard; Dasen, Emily J; Link, Charles J; Das, Rituparna; Xu, Zhi Jin; Sheldon, Eric A; Nowak, Teresa A; Monath, Thomas P

2017-08-01

The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log 10 dose range in two sequential cohorts. In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 10 3 , 3 × 10 4 , 3 × 10 5 , or 3 × 10 6 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 10 6 , 9 × 10 6 , 2 × 10 7 , or 1 × 10 8 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 10 3 [n=64], 3 × 10 4 [n=64], 3 × 10 5 [n=64], or 3 × 10 6 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 10 6 [n=20], 9 × 10 6 [n=47], 2 × 10 7 [n=47], or 1 × 10 8 PFU [n=48]) and 20 received placebo. Most

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial

Directory of Open Access Journals (Sweden)

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.

Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies.

Science.gov (United States)

Yue, Yong; Collaku, Agron; Brown, Jean; Buchanan, William L; Reed, Kenneth; Cooper, Stephen A; Otto, James

2013-09-01

Paracetamol (APAP), also known as acetaminophen, is the most commonly used over-the-counter analgesic for the treatment of mild-to-moderate pain. However, the speed of onset of pain relief is limited mainly to the standard, immediate-release formulation. Efficacy and speed of onset of pain relief are critical in acute pain situations such as postsurgical dental pain, because reducing pain can improve clinical outcome and reduce the risk of transition from acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of excessive dosing with the analgesic. We sought to investigate the dose-response efficacy and speed of onset of pain relief of a fast-dissolving APAP formulation compared with lower doses of APAP and placebo in dental patients after impacted third molar extraction. Two single-center, single-dose, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies (Study I and Study II) were conducted to evaluate the efficacy and speed of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD-APAP), standard APAP, and placebo in patients with postsurgical dental pain following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg, FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 patients. All 701 patients from both studies were included in the analysis and safety assessment. FD-APAP 1000 mg demonstrated significantly greater effect compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy measurements, including sum of pain relief and pain intensity difference, total pain relief, sum of pain intensity difference, pain intensity difference, and pain relief score during 6 hours after the dose. Onset of confirmed first perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which was 32% and 25% significantly shorter than onset of pain relief of FD

Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study.

Science.gov (United States)

Jones, David; Boudes, Pol F; Swain, Mark G; Bowlus, Christopher L; Galambos, Michael R; Bacon, Bruce R; Doerffel, Yvonne; Gitlin, Norman; Gordon, Stuart C; Odin, Joseph A; Sheridan, David; Wörns, Markus-Alexander; Clark, Virginia; Corless, Linsey; Hartmann, Heinz; Jonas, Mark E; Kremer, Andreas E; Mells, George F; Buggisch, Peter; Freilich, Bradley L; Levy, Cynthia; Vierling, John M; Bernstein, David E; Hartleb, Marek; Janczewska, Ewa; Rochling, Fedja; Shah, Hemant; Shiffman, Mitchell L; Smith, John H; Choi, Yun-Jung; Steinberg, Alexandra; Varga, Monika; Chera, Harinder; Martin, Robert; McWherter, Charles A; Hirschfield, Gideon M

2017-10-01

Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice-web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the

Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study.

Science.gov (United States)

Ascher, B; Hoffmann, K; Walker, P; Lippert, S; Wollina, U; Havlickova, B

2014-12-01

Unwanted submental fat (SMF) may result in an unattractive chin profile and dissatisfaction with appearance. An approved and rigorously tested non-surgical method for SMF reduction is lacking. To evaluate the efficacy and safety of ATX-101 for the pharmacological reduction of unwanted SMF in a phase III randomized, double-blind, placebo-controlled study. Patients (n = 360) with moderate or severe SMF were randomized to receive ATX-101 1 or 2 mg/cm(2) or placebo injected into their SMF for up to four treatments ~28 days apart, with a 12-week follow-up. Coprimary efficacy endpoints were the proportions of treatment responders, defined as a ≥1-point reduction in SMF on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS), and those satisfied with their appearance in association with their face and chin after treatment on the Subject Self-Rating Scale (SSRS score ≥4). Secondary efficacy endpoints included a ≥1-point improvement in SMF on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and changes in the Patient-Reported Submental Fat Impact Scale (PR-SMFIS). Additional patient-reported outcomes and changes in the Skin Laxity Rating Scale were recorded. Adverse events (AEs) and laboratory test results were monitored. Compared with placebo, a greater proportion of patients treated with ATX-101 1 and 2 mg/cm(2) showed a ≥1-point improvement in CR-SMFRS (58.3% and 62.3%, respectively, vs. 34.5% with placebo; P < 0.001) and patient satisfaction (SSRS score ≥4) with the appearance of their face and chin (68.3% and 64.8%, respectively, vs. 29.3%; P < 0.001). Patient-reported secondary efficacy endpoints showed significant improvements in SMF severity (PR-SMFRS; P = 0.009 for ATX-101 1 mg/cm(2) , P < 0.001 for ATX-101 2 mg/cm(2) vs. placebo) and emotions and perceived self-image (PR-SMFIS; P < 0.001). No overall worsening of skin laxity was observed. AEs were mostly transient, mild to moderate in intensity and localized to the treatment area. ATX

Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT).

Science.gov (United States)

Ramadan, Ronnie; Dhawan, Saurabh S; Binongo, José Nilo G; Alkhoder, Ayman; Jones, Dean P; Oshinski, John N; Quyyumi, Arshed A

2016-04-01

Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function. Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis

Prophylactic gabapentin for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: A randomized, double-blind, placebo-controlled study

Directory of Open Access Journals (Sweden)

Pandey Chandra

2006-01-01

Full Text Available Background: Gabapentin is an antiepileptic drug. Its antiemetic effect is demonstrated in chemotherapy-induced acute and delayed onset of nausea and vomiting in breast cancer patients. Aim: To evaluate the antiemetic effect of gabapentin on incidence and severity of postoperative nausea and vomiting in laparoscopic cholecystectomy. Settings and Design: Double-blind, randomized, placebo-controlled study. Materials and Methods: Two hundred and fifty patients of ASA physical status I and II, scheduled for laparoscopic cholecystectomy were randomly assigned into two equal groups to receive 600 mg gabapentin or matching placebo two hours before surgery. Standard anaesthesia technique was used. Fentanyl was used as rescue postoperative analgesic. Ondansetron 4 mg was used intravenously as rescue medication for emesis. The total number of patients who had nausea or vomiting, and its severity and total fentanyl consumption in the first 24 hours were recorded. Statistical Analysis: "Z test" was used to test the significance of severity of post-operative nausea and vomiting between groups. Fentanyl consumed in each group (Mean±SD within 24 hrs was compared using student t test. P value< 0.05 was considered significant. Results: There were no demographic difference between the two groups. Incidence of post-operative nausea and vomiting within 24 hrs after laparoscopic cholecystectomy was significantly lower in gabapentin group (46/125 than in the placebo group (75/125 (37.8% vs 60%; P =0.04. There was a significantly decreased fentanyl consumption in gabapentin group (221.2±92.4 µg as compared to placebo group (505.9±82.0 µg; P =0.01. Conclusion: Gabapentin effectively suppresses nausea and vomiting in laparoscopic cholecystectomy and post-operative rescue analgesic requirement.

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

Science.gov (United States)

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

Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study.

Science.gov (United States)

Tauber, Joseph; Karpecki, Paul; Latkany, Robert; Luchs, Jodi; Martel, Joseph; Sall, Kenneth; Raychaudhuri, Aparna; Smith, Valerie; Semba, Charles P

2015-12-01

Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. Adults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0-4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0-100 visual analogue scale [VAS]). Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0-4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in the study eye, and nasal conjunctival lissamine green staining score (0-4 scale) in the study eye. Treatment-emergent adverse events (TEAEs) were recorded. A total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51-16.70; P < 0.0001). There was no between-group difference in inferior corneal staining (treatment effect, 0.03; 95% CI, -0.10 to 0.17; P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P < 0.0001). There were no between-group differences on secondary signs: total corneal staining and nasal lissamine staining. More

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.

Science.gov (United States)

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.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

Science.gov (United States)

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…

Atomoxetine hydrochloride in the treatment of children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: A placebo-controlled Italian study.