Leptin in Human Energy and Neuroendocrine Homeostasis
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|ClinicalTrials.gov Identifier: NCT00265980|
Recruitment Status : Terminated (Closed by sponsor. Lack of funding.)
First Posted : December 15, 2005
Results First Posted : September 18, 2019
Last Update Posted : September 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Obesity Weight Loss||Drug: Subcutaneous Placebo Drug: Leptin||Not Applicable|
The failure of obesity treatments to sustain weight reduction is widely recognized. The central hypotheses of these studies are that: 1) Energy and neuroendocrine homeostatic systems are altered during the maintenance of a reduced body weight in a manner that favors weight regain; 2) These changes occur because weight-reduced individuals are in a state of relative leptin deficiency due to loss of body fat; and 3) Therefore these changes accompanying the maintenance of a reduced body weight will be reversed if circulating leptin concentrations are restored to those that were present prior to weight reduction. Maintenance of a reduced body weight is associated with integrated autonomic and neuroendocrine changes that reduce energy expenditure and increase food intake in a manner that is similar to that seen in rodents and humans who are deficient in, or resistant to, the adipocyte-derived hormone leptin.
Systemic leptin administration to leptin-deficient rodents and humans reverses the metabolic (hypometabolism, hyperphagia), autonomic (increased parasympathetic and decreased sympathetic nervous system tone), and neuroendocrine changes that characterize the leptin-deficient state. The proposed studies focus on the neuroendocrine, autonomic, and metabolic changes that characterize the reduced-obese individual, and the effects on these phenotypes of restoration of circulating concentrations of leptin to levels present prior to weight loss.
Healthy lean and overweight subjects are admitted to the General Clinical Research Center at Columbia University Medical College and placed on a liquid formula diet. Calories are adjusted until weight is stable and then subjects undergo testing of neuroendocrine, autonomic, and metabolic function. All subjects undergo an in-patient 10% weight reduction. Subjects are studied in a single blind placebo control design in which they are studied at usual weight and while maintaining a 10% reduced weight. At either usual weight or reduced state subjects undergo a single blind crossover placebo/control study in which they receive placebo, leptin injections while on an isocaloric diet either at usual weight or following a 10% weight loss.
During each of these study periods, subjects will undergo detailed evaluation of 1) energy expenditure; 2) autonomic nervous system tone (serial blockade of sympathetic and parasympathetic inputs, heart rate variability analyses, and urinary catecholamine excretion); 3) hypothalamic-pituitary-thyroid, -adrenal and -gonadal, axis function; 4) adipose tissue gene expression; 5) other molecules (e.g., adiponectin, ghrelin, PYY) that may influence neuroendocrine and metabolic function. The results of these studies will further delineate the physiology of body weight regulation and of leptin.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Randomized, single-blind, crossover study: half of the subjects had placebo first and half had leptin first. The order does not affect data analysis.|
|Official Title:||Leptin in Human Energy and Neuroendocrine Homeostasis|
|Actual Study Start Date :||July 2002|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||July 2013|
No Intervention: Weight initial
Subjects undergo studies at their usual body weight which is used as a baseline against which to compare subjects following weight loss with or without leptin repletion.
Placebo Comparator: Weight -10% placebo
Subjects are studied while at a 10% reduced body weight and receiving placebo injections for 5 weeks.
Drug: Subcutaneous Placebo
Twice daily injections of saline in the same volume as will be used for leptin injections.
Other Name: Saline
Experimental: Weight -10% leptin
Subjects are studied while at a 10% reduced body weight and receiving leptin injections for 5 weeks.
Leptin will be given as twice daily subcutaneous injections in doses titrated to replicate 8 a.m. circulating leptin concentrations measured in the same subjects prior to weight loss.
Other Name: Metreleptin
- Total Energy Expenditure (TEE) [ Time Frame: Baseline, 11 weeks, 18 weeks ]To measure the metabolic changes associated with maintenance of a reduced body weight (in kcal/day)
- TEE/FFM [ Time Frame: Baseline, 11 weeks, 18 weeks ]To measure the total energy expenditure/fat-free mass (FFM) (in kcal/kg).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00265980
|United States, New York|
|New York, New York, United States, 10032|
|Principal Investigator:||Michael Rosenbaum, MD||Columbia University|