Role of Leptin in the Neuroendocrine and Immune Response to Fasting

Phase 1

Completed

• Conditions: Fasting
• Interventions: Drug: r-metHuLeptin; Other: placebo

• Registration Number: NCT00140231
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

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

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

Study Timeline

• Study Start: 2002-10
• Study First Submitted: 2005-08-30
• Study First Submitted QC: 2005-08-30
• Study First Posted: 2005-09-01
• Primary Completion: 2011-03
• Results First Submitted: 2015-12-29
• Study Completion: 2016-12
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-05
• Last Update Submitted: 2017-05-05
• Results First Posted: 2017-06-07
• Last Update Posted: 2017-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Metreleptin	r-metHuLeptin	r-metHuLeptin self-administered subcutaneously
Metreleptin	placebo	r-metHuLeptin self-administered subcutaneously
Placebo	placebo	Placebo, administered in same method as active arm.
Placebo	r-metHuLeptin	Placebo, administered in same method as active arm.

Primary Outcome Measures

Name	Time	Method
Cortisol	four days
ACTH Mean Level	4 days	Response of ACTH to leptin administration in fed and fasting state from baseline was measured
Immune Function CD3 Count	4 days

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States