Leptin in Human Energy and Neuroendocrine Homeostasis
|ClinicalTrials.gov Identifier: NCT00265980|
Recruitment Status : Unknown
Verified March 2015 by Michael Rosenbaum, Columbia University.
Recruitment status was: Active, not recruiting
First Posted : December 15, 2005
Last Update Posted : April 1, 2015
Previous work in our laboratory, and many others, has shown that body weight is regulated. When anyone, fat or thin, tries to maintain a reduced body weight, many systems affecting energy balance (skeletal muscle, neuroendocrine, and autonomic systems) conspire to slow metabolic rate thus favoring the regain of lost weight. Individuals with leptin deficiency are remarkably similar to weight-reduced individuals. Their metabolism, thyroid hormones, and sympathetic nervous system activity are all low despite their obesity. While administration of leptin to leptin-deficient humans results in substantial weight loss and increases in energy expenditure. However, leptin administration to leptin-sufficient humans at usual body weight has little or no effect on weight unless given in doses 10-20 times what would be considered to be in the normal physiological range. This study examines the hypothesis that leptin is "read" by various systems regulating energy balance as an indicator of how much energy we have stored and that the body perceives the weight-reduced state as a condition of relative leptin insufficiency. Within this model, restoration of leptin to levels present prior to weight loss should relieve much of the metabolic opposition to keeping weight off. Preliminary studies support this hypothesis.
Healthy lean and overweight subjects are admiited 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,lepin injections while on an isocaloric diet either at usual weight or following a 10% weight loss. Leptin injections are given in doses that restored 8AM circulating leptin concentrations to those present at initial body weight.
|Condition or disease||Intervention/treatment||Phase|
|Obesity Weight Loss||Drug: Placebo Drug: Leptin Drug: placebo Drug: Tri-iodothyronine||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||Leptin in Human Energy and Neuroendocrine Homeostasis|
|Study Start Date :||July 2002|
|Estimated Primary Completion Date :||September 2015|
|Estimated Study Completion Date :||June 2016|
No Intervention: A: Baseline studies
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 tri-iodothyronine or leptin repletion.
Placebo Comparator: B -1: Subcutaneous placebo
Subjects are studied while at a 10% reduced body weight and receiving twice daily doses of placebo for 5 weeks. Data from this phase of the study are compared to baseline arm (A) to examine the effects of weight loss without leptin repletion.
twice daily iinjections of saline in the same volume as will be used for B-2 leptin injections
Other Name: Saline
Experimental: B-2: Leptin repletion
Subjects are studied while at a 10% reduced body weight and receiving twice daily injections of "replacement" leptin for 5 weeks. Data from this phase of the study are compared to placebo arm (B-1) to examine the effects of of leptin repletion in weight-reduced subjects.
Leptin will be given as twice daily subcutaneous injections in doses titrated to replicate 8AM circulating leptin concentrations measured in the same subjects prior to weight loss.
Other Name: Metreleptin
Placebo Comparator: C-1: Oral placebo
Subjects are studied while at a 10% reduced body weight and receiving an oral placebo for 5 weeks. Data from this phase of the study are compared to baseline arm (A) to examine the effects of weight loss without thyroid repletion.
Subjects will receive a once daily oral placebo that looks identical to the tri-iodothyronine administered in arm C-2.
Experimental: C-2: Tri-iodothyronine repletion
Subjects are studied while at a 10% reduced body weight and receiving an oral "replacement" of tri-idothyronine for 5 weeks. Data from this phase of the study are compared to placebo arm (C-1) to examine the effects of of thyroid repletion in weight-reduced subjects.
Subjects will receive a once daily oral dose of T3 which will be titrated until 8AM T3 levels are similar to those measured in the same subjects prior to weight loss.
Other Name: Cytomel
- Reversal of metabolic changes associated with maintenance of a reduced body weight. [ Time Frame: End of study ]
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:||Rudolph L Leibel, M.D.||Columbia University|
|Principal Investigator:||Michael Rosenbaum, M.D.||Columbia University|