Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study

JAMA. 2003 Apr 9;289(14):1826-32. doi: 10.1001/jama.289.14.1826.


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 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 subcutaneous injections of placebo (n = 32) or 0.3 microg/kg (n = 32), 1.0 microg/kg (n = 38), or 2.0 microg/kg (n = 33) of rhvCNTF. Another group received 1.0 microg/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 microg/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- microg/kg, 8 (29.6%) in the 1.0- microg/kg, and 5 (26%) in the 2.0- microg/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 event.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / therapeutic use*
  • Body Mass Index
  • Caloric Restriction
  • Ciliary Neurotrophic Factor / administration & dosage
  • Ciliary Neurotrophic Factor / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Insulin / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / drug therapy*
  • Recombinant Proteins / therapeutic use
  • Weight Loss / physiology


  • Anti-Obesity Agents
  • Ciliary Neurotrophic Factor
  • Insulin
  • Lipids
  • Recombinant Proteins
  • axokine