Overweight
Conditions
Keywords
Roux-en-Y gastric bypass, Leptin, Bariatric surgery, Overweight after Roux-en-Y gastric bypass surgery
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.
Interventions
DRUGLeptin
Leptin self-administered subcutaneously at 0.05 mg/kg body weight twice each day
OTHERPlacebo
Sterile water equal in volume to that of the metreleptin dose calculated for each individual self-administered subcutaneously twice each day
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Amylin Pharmaceuticals, LLC.
National Center for Research Resources (NCRR)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight Change (in kg.) After Each Intervention | 0 weeks, 16 weeks and 32 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leptin - Placebo Leptin self-administered subcutaneously twice each day for 16 weeks, then Placebo for 16 weeks. | 15 |
| Placebo - Leptin Placebo self-administered subcutaneously twice each day for 16 weeks, then Leptin for 16 weeks. | 16 |
| Total | 31 |
Baseline characteristics
| Characteristic | Placebo - Leptin | Leptin - Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Continuous | 42.76 Years | 50.93 Years | 47 Years |
| Region of Enrollment United States | 16 participants | 15 participants | 31 participants |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 27 | 4 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
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.
Time frame: 0 weeks, 16 weeks and 32 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Leptin Intervention | Weight Change (in kg.) After Each Intervention | -0.39 kg weight change |
| Placebo Intervention | Weight Change (in kg.) After Each Intervention | 0.02 kg weight change |