Placebo Control (placebo + control)

Distribution by Scientific Domains

Selected Abstracts

Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects

M. Bayerle-Eder
Abstract Background, Free fatty acids (FFAs) and triglycerides (TGs) can cause vascular dysfunction and arteriosclerosis. Acute elevation of plasma FFA and TG concentration strongly increase ocular and skin blood flow. This study was designed to discriminate whether FFA or TG independently induce hyperperfusion by measuring regional and systemic haemodynamics. Methods, In a balanced, randomized, placebo-controlled, double-blind, three-way, crossover study nine healthy subjects received either Intralipid® (Pharmacia and Upjohn, Vienna, Austria) with heparin, Intralipid® alone or placebo control. Pulsatile choroidal blood flow was measured with laser interferometry, retinal blood flow and retinal red blood cell velocity with laser Doppler velocimetry, and skin blood flow with laser Doppler flowmetry during an euglycaemic insulin clamp. Results, A sevenfold increase of FFA during Intralipid®/heparin infusion was paralleled by enhanced choriodal, retinal, and skin blood flow by 17 ± 4%, 26 ± 5% (P < 0·001), and 47 ± 19% (P = 0·03) from baseline, respectively. In contrast, a mere threefold increase of FFA by infusion of Intralipid® alone did not affect outcome parameters, despite the presence of plasma TG levels of 250,700 mg dL,1; similar to those obtained during combined Intralipid®/heparin infusion. Systemic haemodynamics were not affected by drug infusion. Conclusions, Present findings demonstrate a concentration-dependent increase in ocular and skin blood flow by FFA independently of elevated TG plasma concentrations. As vasodilation of resistance vessels occur rapidly, FFA may play a role in the development of continued regional hyperperfusion and deteriorate microvascular function. [source]

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

Robert J. Amdur M.D.
Abstract 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. © 2001 Wiley-Liss, Inc. [source]

Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin,

L. R. Robinson
Synopsis The palmitoyl pentapeptide palmitoyl-lysine-threonine-threonine-lysine-serine (pal-KTTKS) is a synthetic material that was designed as a topical agent to stimulate collagen production and thus provide a skin anti-wrinkle benefit. To determine if pal-KTTKS is effective, the clinical study reported here was conducted. Caucasian female subjects (n = 93, aged 35,55) participated in a 12-week, double-blind, placebo-controlled, split-face, left,right randomized clinical study assessing two topical products: moisturizer control product vs. the same moisturizer product containing 3 ppm pal-KTTKS. Pal-KTTKS was well tolerated by the skin and provided significant improvement vs. placebo control for reduction in wrinkles/fine lines by both quantitative technical and expert grader image analysis. In self-assessments, subjects also reported significant fine line/wrinkle improvements and noted directional effects for other facial improvement parameters. Résumé Le pentapeptide palmitoyl-lysine-thréonine-lysine-sérine (pal-KTTKS) est un composé synthétique décrit comme agent topique stimulant la production de collagène et possédant donc des propriétés anti-rides. L'efficacité du pal-KTTKL a étéévaluée dans l'étude clinique faisant l'objet de cet article. Des femmes de type caucasien (n = 93, de 35 à 55 ans) ont participé pendant 12 semaines à un test en double aveugle avec placébo, en apparié par demie face comparant deux produits topiques: un produit témoin hydratant et le même produit contenant 3 ppm de pal-KTTKS. Bien toléré par la peau, le pal-KTTKS a montré par rapport au témoin, une amélioration significative dans la réduction des rides et ridules que se soit par des techniques quantitatives et par l'analyse d'image quantifiée par un expert. Dans le cadre d'auto-évaluations, les sujets ont fait état d'améliorations significatives et attiré l'attention sur des effets pouvant servir de pistes pour d'autres paramètres d'amélioration faciale. [source]

Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial

Rob McCarney
Abstract Objectives Doubt over the cost-effectiveness of the cholinesterase inhibitors in dementia has renewed interest in alternative treatments such as Ginkgo biloba. We aimed to determine the effectiveness and the safety profile of Ginkgo biloba for treating early stage dementia in a community setting. Methods We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120,mg daily) or a placebo control for 6 months. Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). Results We recruited 176 participants, mainly through general practices. In the ANCOVA model with baseline score as a co-variate (n,=,176), Ginkgo did not have a significant effect on outcome at six months on either the ADAS-Cog score (p,=,0.392), the participant-rated QOL-AD score (p,=,0.787) nor the carer-rated QOL-AD score (p,=,0.222). Conclusion We found no evidence that a standard dose of high purity Ginkgo biloba confers benefit in mild-moderate dementia over 6 months. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Randomization in psychiatric intervention research in the general practice setting

CM Van Der Feltz-Cornelis Faculty of Medicine
Abstract Most studies of psychiatric interventions in general practice settings conform only in part to the requirements of randomization, placebo control and blinding as formulated by the Cochrane Collaboration. It is possible, nonetheless, to develop experimental research designs that are sufficiently near to this standard. These must deal with certain methodological issues specific to psychiatric research. This article discusses scientific standards of psychiatric research with special consideration of interventions in general practice settings. These issues are accompanied by concrete examples and suggestions on how to confront the problems. In psychiatric intervention research, equivalence studies with single-blind outcome assessment, a tested and ethically justified method, are generally used in place of placebo-controlled studies. The article also examines randomization procedures in greater depth. Randomization can be applied across trial subjects or across doctors' practices. Practical consequences of randomizing across subjects, and specific implementations of it such as crossover and pre-post designs in general practice settings, are clarified. Overall, a research design using randomization across doctors' practices is judged preferable to one that randomizes across trial subjects. One potential problem is that the control group may become too small, especially when considerable effects are expected from the intervention being studied. One might consider making the control condition smaller in the first place, or, if indicated on ethical grounds, performing an intermediate analysis and then breaking off the study as soon as a statistically significant effect has been demonstrated. Multilevel statistical techniques offer new opportunities for analysis within such designs. Copyright © 2000 Whurr Publishers Ltd. [source]

Pivotal studies of orphan drugs approved for neurological diseases,

Jun Mitsumoto MPH
Objective To identify design elements of clinical trials leading to US Food and Drug Administration approval of drugs for neurological diseases with and without orphan indications. Methods We used publicly available information to identify approvals for drugs for neurological diseases with an orphan indication (n = 19) and compared them with recent approvals for drugs for neurological diseases without an orphan indication (n = 20). We identified "pivotal trials" from drug labels and drug approval packages, and assessed them on four elements of clinical trial design: control, blinding, randomization, and size. Results All drugs for neurological diseases (100%) approved without an orphan indication included at least two randomized, double-blind, placebo-controlled trials. In comparison, 32% of drugs with an orphan indication had at least two such trials (p < 0.001) and 74% had at least one (p = 0.02). Thirty-three pivotal trials were conducted for the 19 drugs approved with an orphan indication. Of the 33 trials, 11 (33%) did not use a placebo control, 9 (27%) were not double blind, and 4 (12%) were not randomized. Drugs approved without an orphan indication had more pivotal trials per drug (3.8 vs 1.7 trials; p < 0.001) and a larger mean trial size (506 vs 164 trial participants; p < 0.001). Interpretation The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy. Ann Neurol 2009;66:184,190 [source]

In Vivo RANK Signaling Blockade Using the Receptor Activator of NF-,B:Fc Effectively Prevents and Ameliorates Wear Debris-Induced Osteolysis via Osteoclast Depletion Without Inhibiting Osteogenesis

Lisa M. Childs
Abstract Prosthesis failure due to wear debris-induced osteolysis remains a major clinical problem and the greatest limitation for total joint arthroplasty. Based on our knowledge of osteoclast involvement in this process and the requirements of receptor activator of NF-,B (RANK) signaling in osteoclastogenesis and bone resorption, we investigated the efficacy of RANK blockade in preventing and ameliorating titanium (Ti)-induced osteolysis in a mouse calvaria model. Compared with placebo controls we found that all doses of RANK:Fc above 1 mg/kg intraperitoneally (ip) per 48 h significantly inhibited osteoclastogenesis and bone resorption in response to Ti implanted locally. Complete inhibition occurred at 10 mg/kg ip per 48 h, yielding results that were statistically equivalent to data obtained with Ti-treated RANK,/, mice. We also evaluated the effects of a single injection of RANK:Fc on day 5 on established osteolysis and found that Ti-treated were still depleted for multinucleated tartrate-resistant acid phosphatase-positive (TRAP+) cells 16 days later. More importantly, this osteoclast depletion did not affect bone formation because the bone lost from the osteolysis on day 5 was restored by day 21. An assessment of the quantity and quality of the newly formed bone in these calvariae by calcein labeling and infrared (IR) microscopy, respectively, showed no significant negative effect of RANK:Fc treatment. These studies indicate that osteoclast depletion via RANK blockade is an effective method to prevent and reverse wear debris-induced osteolysis without jeopardizing osteogenesis. [source]

A meta-analysis of the effects of internet- and computer-based cognitive-behavioral treatments for anxiety

Mark A. Reger
Abstract Internet-and computer-based cognitive-behavioral treatments have been introduced as novel approaches to deliver standard, quality treatment that may reduce barriers to care. The purpose of this review is to quantitatively summarize the literature examining the treatment effects of Internet- or computer-based treatment (ICT) on anxiety. Nineteen randomized controlled ICT trials were identified and subjected to fixed and random effects meta-analytic techniques. Weighted mean effect sizes (Cohen's d) showed that ICT was superior to waitlist and placebo assignment across outcome measures (ds=.49,1.14). The effects of ICT also were equal to therapist-delivered treatment across anxiety disorders. However, conclusions were limited by small sample sizes, the rare use of placebo controls, and other methodological problems. In addition, the number of available studies limited the opportunity to conduct analyses by diagnostic group; there was preliminary support for the use of ICT for panic disorder and phobia. Large, well-designed, placebo-controlled trials are needed to confirm and extend the results of this meta-analysis. © 2008 Wiley Periodicals, Inc. J Clin Psychol 65: 1,21, 2009. [source]

Roles of Corticotropin-Releasing Factor, Neuropeptide Y and Corticosterone in the Regulation of Food Intake In Xenopus laevis

E. J. Crespi
Abstract In mammals, hypothalamic control of food intake involves counterregulation of appetite by anorexigenic peptides such as corticotropin-releasing factor (CRF), and orexigenic peptides such as neuropeptide Y (NPY). Glucocorticoids also stimulate food intake by inhibiting CRF while facilitating NPY actions. To gain a better understanding of the diversity and evolution of neuroendocrine feeding controls in vertebrates, we analysed the effects of CRF, NPY and glucocorticoids on food intake in juvenile Xenopus laevis. We also analysed brain CRF and NPY mRNA content and plasma corticosterone concentrations in relation to nutritional state. Intracerebroventricular (i.c.v.) injection of ovine CRF suppressed food intake while CRF receptor antagonist ,helical CRF(9,41) significantly increased food intake relative to uninjected and placebo controls. By contrast, i.c.v. injection of frog NPY and short-term corticosterone treatment increased food intake. Semi-quantitative reverse transcription-polymerase chain reaction analyses showed that CRF and NPY mRNA fluctuated with food intake in the brain region containing the mid-posterior hypothalamus, pretectum, and optic tectum: CRF mRNA decreased 6 h after a meal and remained low through 31 days of food deprivation; NPY mRNA content also decreased 6 h after a meal, but increased to prefeeding levels by 24 h. Plasma corticosterone concentration increased 6 h after a meal, returned to prefeeding levels by 24 h, and did not change with prolonged food deprivation. This postprandial increase in plasma corticosterone may be related to the subsequent increase in plasma glucose and body water content that occurs 24 h postfeeding. Overall, our data support the conclusion that, similar to other vertebrates, CRF is anorexigenic while NPY is orexigenic in X. laevis, and CRF secretion modulates food intake in the absence of stress by exerting an inhibitory tone on appetite. Furthermore, the stress axis is activated in response to food intake, but in contrast to mammals and birds is not activated during periods of food deprivation. [source]

Double-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone Pain

T.M. Fan
Background: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. Hypothesis: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. Animals: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. Methods: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. Results: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation ,112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. Conclusions and Clinical Importance: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment. [source]

Neoadjuvant antiangiogenic therapy with tamoxifen does not impair gastrointestinal anastomotic repair in the rat

D. A. McNamara
Abstract Introduction Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing. We hypothesised that tamoxifen would not adversely affect skin wound and gut anastomotic healing. Methods A previously established model of tamoxifen, administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was used. Animals received two days pretreatment prior to laparotomy and small bowel anastomosis. Treatment was continued until completion of the study. The principal outcome measures are survival, macroscopic wound and anastomotic healing, anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP) content. Results Tamoxifen treated animals had fewer complications of skin wound healing than controls (4.5%vs. 19.5%; ,2 4.65, 1 d.f., P < 0.05). There was no significant difference in adhesion formation or macroscopic complications of anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen treated animals at postoperative day 3 (39 ± 4.4 vs. 22.5 ± 3.5 mmHg; P < 0.01) and equal to that of controls on postoperative day 5 (144.4 ± 9.4 vs. 127.3 ± 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly less than placebo controls from postoperative day 3 with no difference in mortality between groups (,2 = 0.06, 1df, P = ns). PVA sponge granuloma OHP content on day 7 was higher in tamoxifen-treated animals (2.93 ± 0.4 vs. 1.4 ± 0.4 mg OHP/mg dry sponge weight; P = 0.03). Conclusion Antiangiogenic therapy with tamoxifen has no demonstrable adverse effects on wound or anastomotic repair and its perioperative use is compatible with successful early surgical outcomes. [source]