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Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant Variant of Ciliary Neurotrophic Factor for Weight Loss in Obese Adults: A Randomized, Dose-Ranging Study. JAMA. 2003;289(14):1826–1832. doi:10.1001/jama.289.14.1826
Author Affiliations: Radiant Research, Stuart, Fla (Dr Ettinger); Piedmont Medical Research Associates, Winston-Salem, NC (Dr Littlejohn); Diabetes & Glandular Disease Clinic, San Antonio, Tex (Dr Schwartz); Radiant Research, San Diego, Calif (Dr Weiss); Tampa Medical Group Research, Tampa, Fla (Dr McIlwain); St Luke's-Roosevelt Hospital, New York, NY (Drs Heymsfield and Heshka); Pennington Biomedical Research Center, Baton Rouge, La (Dr Bray); Celeris Corp, Rockville, Md (Dr Heyman); Regeneron Pharmaceuticals Inc, Tarrytown, NY (Drs Roberts and Guler and Mss Stambler and Vicary).
Context Obese individuals tend to resist the weight-regulating effects of exogenously
administered leptin. A genetically engineered recombinant human variant ciliary
neurotrophic factor (rhvCNTF) that signals through leptinlike pathways in
the hypothalamus has been shown to bypass leptin resistance in animal models
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 subcutaneous
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 Organization formula minus 500 kcal/d).
Main Outcome Measures Change in weight during the 12-week double-blind treatment 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 frequently reported adverse
Conclusions In this initial, dose-ranging, 12-week study, treatment with rhvCNTF
resulted in more weight loss than placebo. These preliminary findings require
confirmation in large prospective clinical trials.
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