Recombinant Variant of Ciliary Neurotrophic Factor for Weight Loss in Obese Adults

Published on Jan 1, 2017
Mark P. Ettinger18
Estimated H-index: 18
Thomas W. Littlejohn4
Estimated H-index: 4
+ 8 AuthorsCatherine Vicary1
Estimated H-index: 1
Context Obese individuals tend to resist the weight-regulating effects of exog- enously administered leptin. A genetically engineered recombinant human variant cili- ary neurotrophic factor (rhvCNTF) that signals through leptinlike pathways in the hy- pothalamus has been shown to bypass leptin resistance in animal models of obesity. Objective To identify a safe and well-tolerated dose of rhvCNTF that causes weight loss in obese adults. Design, Setting, and Patients Twelve-week, double-blind, randomized, parallel- group, dose-ranging, multicenter clinical trial conducted at 2 university obesity clinics and at 5 independent clinical research clinics from March 2000 to August 2001, and including 173 nondiabetic obese adults, 82.6% of whom were women, with a mean (SD) body mass index of 41.1 (4.1). Interventions Patients were randomly assigned to receive daily for 12 weeks sub- cutaneous injections of placebo (n=32) or 0.3 µg/kg (n=32), 1.0 µg/kg (n=38), or 2.0 µg/kg (n=33) of rhvCNTF. Another group received 1.0 µg/kg for 8 weeks and placebo for 4 weeks (n=38), but they were not included in the primary analysis. All participants received instructions for a reduced-calorie diet (World Health Organiza- tion formula minus 500 kcal/d). Main Outcome Measures Change in weight during the 12-week double-blind treat- ment period and proportion of patients who achieved a weight loss of at least 5%. Results Of the 173 randomized patients, 123 (71%) completed the double-blind dosing period. Mean (SEM) changes in kilograms from baseline body weights were 0.1 (0.6) for placebo and �1.5 (0.6) for the 0.3, �4.1 (0.6) for the 1.0, and -3.4 (0.7) for the 2.0 µg/kg of rhvCNTF dosage groups (P.001, test for trend). Two patients (8.7%) in the placebo and 2 (8.3%) in the 0.3-µg/kg, 8 (29.6%) in the 1.0-µg/kg, and 5 (26%) in the 2.0-µg/kg treatment groups achieved a weight loss of at least 5%. Recombinant human variant CNTF was generally well tolerated although adverse events occurred in 75% of patients receiving placebo and 78% to 93% of patients receiving rhvCNTF, in a dose-related fashion, with mild injection site reactions as the most fre- quently reported adverse event. Conclusions In this initial, dose-ranging, 12-week study, treatment with rhvCNTF resulted in more weight loss than placebo. These preliminary findings require confir- mation in large prospective clinical trials.
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