Leptin in the Maintenance of Reduced Body Weight
Condition: Obesity
MeSH terms: Body Weight
Study type: Interventional
Phase: Phase 2

Summary: 
      You are invited to take part in a research study about the role of leptin (a fat cell hormone
      that normally circulates in the blood) on maintaining a reduced body weight. This study will
      also evaluate how leptin impacts hormone levels, metabolic rate (how many calories are used
      at rest), autonomic nervous function (the part of your brain that controls your heart rate
      and breathing), changes in body composition and your sense of appetite. Under normal
      conditions, leptin is secreted by fat cells and signals to the brain to decrease appetite and
      regulate energy usage and hormone levels. When obese individuals lose weight, their leptin
      levels go down, which may cause them to later regain the weight. This study will provide
      leptin as an investigational medication (not yet approved by the Food and Drug
      Administration) to increase the levels of the leptin hormone that normally circulates in your
      blood back to a normal range. We will see if this can help you to maintain your reduced body
      weight and improve your hormonal and metabolic function.
    

Detailed description: 
      Study Overview This study is a randomized, double-blind, placebo-controlled study of leptin
      administration to individuals with a recent 10% weight loss, achieved through lifestyle
      intervention program. In this study proposal, we propose that 90 subjects who have recently
      completed a lifestyle intervention weight loss program (at one of the four participating
      Boston Weight loss centers) and have achieved a weight loss of more than 10% body weight will
      be enrolled in the study. They will have baseline studies performed (including full
      neuroendocrine evaluation as described below) and will be randomized to leptin/placebo in the
      ratio 1:1 after stratification by center. They will continue to receive standard weight
      maintenance advice with intermittent nutrition and behavioral counseling. Our aim is to
      finally study a total of 36 subjects per treatment arm (20% drop out or inability to achieve
      and/or maintain10% weight loss expected). Leptin levels will be checked every month and the
      dose will be titrated to achieve and keep serum levels equivalent to those at baseline based
      on baseline weight. We will start the leptin/placebo at a dose of 0.08mg/kg fat mass in men
      and 0.14mg/kg fat mass in women, with dose titration to achieve baseline leptin levels
      utilizing formulas derived from our pharmacokinetic studies Leptin levels will be checked
      every month. Circulating leptin levels between +30% and -10% of baseline will be considered
      acceptable. Otherwise, the leptin dose will be adjusted accordingly. Our aim is to keep the
      mean leptin level at or within +30% of baseline. Subjects will be studied prior to receiving
      leptin, after four weeks and six months of weight maintenance and we will compare changes in
      body weight and composition, neuroendocrine function, and metabolic function between the
      leptin and placebo-treated groups. In addition, the first 23 subjects per group will have
      measurement of total energy expenditure performed using doubly labeled water at baseline and
      6 months. This will allow us to examine the effects of leptin replacement, to levels observed
      at baseline body weight, on the maintenance of weight loss and the neuroendocrine and
      metabolic adaptation to decreasing body weight in obese individuals. While difference in
      weight maintenance at six months will be our primary outcome, subjects will also be studied
      after 4 weeks of weight maintenance, which will allow us to determine the role of leptin in
      the adaptation to weight loss under stable, weight maintenance conditions. We have chosen the
      four week time point as previous nonrandomized, uncontrolled studies have been able to
      document an effect of leptin replacement after this time. Both groups will be followed for an
      extended 6-month period during which they will receive standard weight maintenance advice, in
      addition to leptin/placebo. We will observe the changes in weight, neuroendocrine function,
      metabolic function and leptin signaling over this time and compare the leptin and placebo
      groups. In this subset of 23 subjects per group we will evaluate energy expenditure by doubly
      labeled water. Finally, subjects will be followed for a further 6 months after the end of the
      study to document further changes in body weight as an additional study outcome.
    

Intervention name(s): Leptin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Hormone - daily self injections for 6 months; Placebo
Other intervention name(s): metreleptin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment