Trial of Leptin Administration After Roux-en-Y Gastric Bypass

Phase 1

Completed

Conditions: Overweight

Interventions: Drug: Leptin
Other: Placebo

Registration Number: NCT00710814

Lead Sponsor: Columbia University

Brief Summary: This is a pilot and feasibility study to examine a novel intervention using leptin in weight-reduced individuals who have undergone bariatric surgery but still remain obese. Leptin, a peptide hormone secreted from adipose tissue, is a regulator of food intake and energy expenditure. Administration of leptin resulted in profound weight reduction in the few reported cases of obese individuals with genetic leptin deficiency. However, most obese people have increased leptin levels. Such individuals are said to be in a "leptin-resistant" state, whereby administration of physiological concentrations of leptin are ineffective at producing significant weight reduction. Roux-en-Y gastric bypass surgery (RYGBP) is more effective than diet alone in producing long-term reduction of body weight. Yet even after surgery there is a plateau in weight loss though the individual may still be obese and have or be at risk for obesity related morbidities. The investigators have shown that plasma leptin levels are significantly lower in women after RYGBP compared with BMI-matched controls. This state of relative hypoleptinemia or leptin insufficiency suggests that post-RYGBP individuals may be in a "leptin-sensitive" state and, thus, would undergo further weight loss when administered doses of leptin that would not normally result in significant weight reduction. This study will examine the effects of leptin administered by self-injection twice per day on body weight and endocrine function. All individuals will received leptin and placebo and different times during the 34 week study period.

Detailed Description: Metreleptin will be self-administered by subcutaneous injection at 0.05 mg/kg body weight twice per day (i.e. at 8 am and 8 pm). This dose was chosen because it would not be expected to cause substantial weight loss in an obese non-surgical population, nor should it incur any substantial injection site reactions. Subjects will receive a demonstration of dose preparation and injection in addition to written instructions with visual aides. After the run-in period, subjects will demonstrate their preparation and injection technique. Placebo injections will consist of sterile water equal in volume to that of the metreleptin dose calculated for each individual. Subjects will be instructed to continue with their current level of physical activity. At week 16, each subject will cross-over to the alternate treatment for an additional 16 weeks.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 31

Inclusion Criteria

Women ages 25-65 years who are 18 months to 15 years Roux-en-Y gastric bypass
Current BMI of 28-50 kg/m2 and a percent total body weight loss from highest pre-surgical weight of >20% and <45%
Must live in the vicinity of New York City to comply with 11 study visits over 34 weeks
Must be willing to self-inject study drug twice per day

Exclusion Criteria

Diabetes
History of plastic surgery

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Leptin - Placebo	Placebo	Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks.
Placebo - Leptin	Leptin	Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks.
Placebo - Leptin	Placebo	Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks.
Leptin - Placebo	Leptin	Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Weight Change (in kg.) After Each Intervention	0 weeks, 16 weeks and 32 weeks	For the Leptin Intervention, 16 week values were compared to baseline for those who received Leptin in the first period, and 32 week values were compared to 16 week values in those who received Leptin in the second period. For the Placebo Intervention, 16 week values were compared to baseline for those who received Placebo in the first period, and 32 week values were compared to 16 week values in those who received Placebo in the second period.

Secondary Outcome Measures