Trial of Leptin Administration After Roux-en-Y Gastric Bypass
Condition: Overweight
MeSH terms: Overweight
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Leptin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day; Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day
Other intervention name(s): metreleptin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Roux-en-Y gastric bypass; Leptin; Bariatric surgery; Overweight after Roux-en-Y gastric bypass surgery