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

NCT ID: NCT00710814

Last Updated: 2015-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2014-07-31

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.

Conditions

Overweight

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Leptin - Placebo

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

Group Type: EXPERIMENTAL

Leptin

Intervention Type: DRUG

Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day

Placebo

Intervention Type: OTHER

Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day

Placebo - Leptin

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

Group Type: PLACEBO_COMPARATOR

Leptin

Intervention Type: DRUG

Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day

Placebo

Intervention Type: OTHER

Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day

Interventions

Leptin

Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day

Intervention Type: DRUG

Placebo

Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day

Intervention Type: OTHER

Other Intervention Names

metreleptin

Eligibility Criteria

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Amylin Pharmaceuticals, LLC.

INDUSTRY

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Judith Korner

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Judith Korner, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

R21DK081050

Identifier Type: NIH

Identifier Source: secondary_id

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UL1RR024156

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAC6692

Identifier Type: -

Identifier Source: org_study_id