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

Effects of Leptin on Body Weight and Neuroendocrine Axes After Gastric Bypass

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.

Study Overview

• Status: Completed
• Conditions: Overweight
• Intervention / Treatment: Drug: Leptin; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leptin - Placebo; Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks.	Drug: Leptin; Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day; Other Names: metreleptin; Other: Placebo; Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day
Placebo Comparator: Placebo - Leptin; Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks.	Drug: Leptin; Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day; Other Names: metreleptin; Other: Placebo; Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Change (in kg.) After Each Intervention	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.	0 weeks, 16 weeks and 32 weeks

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Research Resources (NCRR); Amylin Pharmaceuticals, LLC.
• Investigators: Principal Investigator: Judith Korner, MD,PhD, Columbia University

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: July 3, 2008
• First Posted (Estimate): July 4, 2008

Study Record Updates

• Last Update Posted (Estimate): November 16, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Bariatric surgery; Leptin; Roux-en-Y gastric bypass; Overweight after Roux-en-Y gastric bypass surgery
• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: AAAC6692; UL1RR024156 (U.S. NIH Grant/Contract); R21DK081050 (U.S. NIH Grant/Contract)