Trial of Leptin Administration After Roux-en-Y Gastric Bypass
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 25 - 65 |
| Updated: | 4/21/2016 |
| Start Date: | April 2008 |
| End Date: | July 2014 |
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.
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.
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.
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.
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
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