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

This study has been completed.
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Amylin Pharmaceuticals, LLC.
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Judith Korner, Columbia University
ClinicalTrials.gov Identifier:
NCT00710814
First received: July 1, 2008
Last updated: October 16, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Overweight
Drug: Leptin
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Leptin on Body Weight and Neuroendocrine Axes After Gastric Bypass

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Weight Change (in kg.) After Each Intervention [ Time Frame: 0 weeks, 16 weeks and 32 weeks ] [ Designated as safety issue: No ]

    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.



Enrollment: 31
Study Start Date: April 2008
Study Completion Date: July 2014
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: metreleptin
Other: Placebo
Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day

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.
  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00710814

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Amylin Pharmaceuticals, LLC.
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Judith Korner, MD,PhD Columbia University
  More Information

Responsible Party: Judith Korner, Associate Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT00710814     History of Changes
Other Study ID Numbers: AAAC6692  R21DK081050  UL1RR024156 
Study First Received: July 1, 2008
Results First Received: August 11, 2015
Last Updated: October 16, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Columbia University:
Roux-en-Y gastric bypass
Leptin
Bariatric surgery
Overweight after Roux-en-Y gastric bypass surgery

Additional relevant MeSH terms:
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on May 03, 2016