Role of Leptin in the Neuroendocrine and Immune Response to Fasting

Study Overview
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Brief Summary
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The purpose of this study will be to determine whether giving leptin (r-metHuLeptin) to a person when he or she is fasting will reverse changes in metabolism, and hormone levels, and immune function associated with fasting, which decreases leptin levels.

Detailed Description
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Leptin is a hormone secreted by fat cells under normal conditions and acts in the brain to decrease appetite and increase energy use. Leptin levels usually go down with fasting. This study will evaluate the secretion of an investigational agent called leptin in lean and overweight individuals while fasting and investigate the potential role of leptin as a regulator of immune function and mediator of the neuroendocrine response to food deprivation in humans. Data derived from these studies will provide insights into the mechanisms underlying altered hormone levels and immune function in malnutrition and obesity and thus may provide the basis for future therapeutic interventions for obesity. Comparison: fed state vs. fasting state vs. fasting + leptin state

Official Title
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Role of Leptin in the Neuroendocrine and Immune Response to Fasting in Humans

Conditions
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Fasting

Intervention / Treatment
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* Drug: r-metHuLeptin
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy lean women (with body mass indices [BMI] < 25 kg/m2) Overweight otherwise healthy men (with BMI > 27 kg/m2) Overweight otherwise healthy women (with BMI > 27 kg/m2). Exclusion Criteria: A history of any illness that may affect the concentrations of the hormones to be studied, e.g. infectious diseases, renal or hepatic failure, type 1 or type 2 diabetes mellitus, cancer or lymphoma, hypogonadism, malabsorption or malnourishment, hypo- or hyperthyroidism, hypercortisolism, alcoholism or drug abuse, anemia, or eating disorder On medications known to affect the hormones to be measured (glucocorticoids, anti-seizure medications, and thyroid hormones) A known history of anaphylaxis or anaphylactoid-like reactions, or a known hypersensitivity to E. coli derived proteins

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metreleptin<br>r-metHuLeptin self-administered subcutaneously | Drug: r-metHuLeptin<br>* recombinant human leptin<br>* Other names: metreleptin;Other: placebo<br>* placebo (no active drug)<br>|
| Placebo Comparator: Placebo<br>Placebo, administered in same method as active arm. | Drug: r-metHuLeptin<br>* recombinant human leptin<br>* Other names: metreleptin;Other: placebo<br>* placebo (no active drug)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol |  | four days | 
| ACTH Mean Level | Response of ACTH to leptin administration in fed and fasting state from baseline was measured | 4 days | 
| Immune Function CD3 Count |  | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| %Fat Mass |  | four days | 
| (RMR) | Resting Metabolic rate using calorimetry | four days | 
| Autonomic Function | aldosterone level were measured on day 4 in response to leptin in fed and fasting states and compared with baseline level on day 1 | four days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leptin, fasting, reproductive, neuroendocrine, immune function, energy deficiency associated with short-term fasting