Pharmacokinetics of Leptin Administration During Fasting

Phase 1

Completed

• Conditions: Energy Deficiency Due to Short-term Fasting
• Interventions: Drug: r-metHuLeptin

• Registration Number: NCT00140205
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

The purpose of this study will be to determine the correct dose of leptin, a natural hormone secreted by the fat cells, to give to people when they are fasting and also to determine whether giving leptin to a person when he or she is fasting will reverse the changes in hormone levels that occur with fasting.

Detailed Description

Leptin is a newly-identified hormone secreted by fat cells under normal conditions that acts in the brain to decrease appetite and increase long term energy usage. Leptin levels usually go down when people are not eating for extended periods of time. Changes in metabolism and certain hormone levels also occur with fasting. By studying the pharmacokinetics of leptin administration, we can evaluate the changes of leptin levels in response to giving different doses of leptin as well as acute changes of other hormones in response to leptin levels. Investigations such as this one have important implications for the future therapeutic use of leptin, including determining the appropriate dose of leptin to use in future studies involving leptin administration.

Comparison: subjects receiving leptin at 3 different doses in the fed state compared to the fasting state

Study Timeline

• Study Start: 2001-02
• Primary Completion: 2004-06
• Study First Submitted: 2005-08-30
• Study First Submitted QC: 2005-08-30
• Study First Posted: 2005-09-01
• Study Completion: 2016-12
• Results First Submitted: 2017-01-06
• Status Verified: 2017-05
• Results First Submitted QC: 2018-01-08
• Last Update Submitted: 2018-01-08
• Results First Posted: 2018-11-02
• Last Update Posted: 2018-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• healthy men with body mass indices (BMI) <25 kg/m2)
• overweight otherwise healthy men with BMI > 27 kg/m2
• healthy lean women with BMI<25 kg/m2
• overweight otherwise healthy women with BMI > 27 kg/m2

Exclusion Criteria

• history of any illness that may affect the concentrations of the hormones that will be studied (such as anemia, infectious diseases, renal or hepatic failure, diabetes mellitus, cancer, lymphoma, hypogonadism, malabsorption or malnourishment, hypo or hyperthyroidism, hypercortisolism, alcoholism or drug abuse, eating disorders)
• on medications known to affect the hormones to be measured in this study (such as glucocorticoids, anti-seizure medications or thyroid hormones)
• known history of anaphylaxis or anaphylactoid-like reactions or who have a known hypersensitivity to E. Coli derived proteins
• women who are breast feeding, pregnant, or wanting to become pregnant during the next 6 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fed state or fasting state	r-metHuLeptin	1-day fed studies with administration of r-metHuLeptin at three different doses (0.01 mg/kg, 0.1 mg/kg, 0.3 mg/kg). All subjects participated in 3 studies in the fed condition (Part A) and 3 separate 72-hour fasting studies. Intervention administered was-r-metreleptin in 3 different doses

Primary Outcome Measures

Name	Time	Method
Leptin Pharmacokinetics Parameters - AUC 72-hour Fasting Day 3 Leptin Dose 0.01 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.01 mg/kg
Leptin Pharmacokinetics Parameters - AUC 24-hour Fed Leptin Dose 0.1 mg/kg	1 DAY	24-hour fed Leptin dose 0.1 mg/kg
Leptin Pharmacokinetic Parameters - TIME(T1/2) / TMAX 24-hour Fed Leptin Dose 0.01 mg/kg	1 DAY	24-hour fed Leptin dose 0.01 mg/kg
Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 72-hour Fasting Day 3 Leptin Dose 0.01 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.01 mg/kg
Leptin Pharmacokinetics Parameters - AUC 72-hour Fasting Day 3 Leptin Dose 0.1 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.1 mg/kg
Leptin Pharmacokinetic Parameters - TIME(T1/2) / TMAX 24-hour Fed Leptin Dose 0.3 mg/kg	1 DAY	24-hour fed Leptin dose 0.3 mg/kg
Leptin Pharmacokinetic Parameters - TIME(T1/2) DAY 3 / TMAX DAY 3 72-hour Fasting Day 3 Leptin Dose 0.3 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.3 mg/kg
Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 72-hour Fasting Day 3 Leptin Dose 0.3 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.3 mg/kg
Leptin Pharmacokinetics Parameters - AUC 24-hour Fed Leptin Dose 0.3 mg/kg	1 DAY	24-hour fed Leptin dose 0.3 mg/kg
Leptin Pharmacokinetic Parameters - TIME(T1/2) DAY 3 / TMAX DAY 3 72-hour Fasting Day 3 Leptin Dose 0.01 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.01 mg/kg
Leptin Pharmacokinetic Parameters TIME(T1/2) DAY 3 / TMAX DAY 3 72-hour Fasting Day 3 Leptin Dose 0.1 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.1 mg/kg
Leptin Pharmacokinetic Parameters - TIME(T1/2) / TMAX 24-hour Fed Leptin Dose 0.1 mg/kg	1 DAY	24-hour fed Leptin dose 0.1 mg/kg
Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 24-hour Fed Leptin Dose 0.1 mg/kg	1 DAY	24-hour fed Leptin dose 0.1 mg/kg
Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 72-hour Fasting Day 3 Leptin Dose 0.1 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.1 mg/kg
Leptin Pharmacokinetics Parameters - AUC 72-hour Fasting Day 3 Leptin Dose 0.3 mg/kg	3 DAY	72-hour fasting Day 3 Leptin dose 0.3 mg/kg
Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 24-hour Fed Leptin Dose 0.3 mg/kg	1 DAY	24-hour fed Leptin dose 0.3 mg/kg
Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 24-hour Fed Leptin Dose 0.01 mg/kg	1 DAY	24-hour fed Leptin dose 0.01 mg/kg
Leptin Pharmacokinetics Parameters - AUC 24-hour Fed Leptin Dose 0.01 mg/kg	1 DAY	24-hour fed Leptin dose 0.01 mg/kg

Secondary Outcome Measures

Name	Time	Method
Cytokine Levels 24h Fed or 72h Fasting for All Different Leptin Doses (0,01-0,1-0,3 mg/kg)	1 DAY or DAY 3	Data were collected neither in Fed nor in Fasting state for the different doses of leptin
Neuroendocrine Hormone Levels 24h Fed or 72h Fasting for All Different Leptin Doses (0,01-0,1-0,3 mg/kg)	1 DAY or DAY 3	Data were collected neither in Fed nor in Fasting state for the different doses of leptin
Adipokine Hormone Levels 24h Fed or 72h Fasting for All Different Leptin Doses (0,01-0,1-0,3 mg/kg)	day 3 of fasting and day 1 of fed state	Data were collected neither in Fed nor in Fasting state for the different doses of leptin

Trial Locations

Locations (1)

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