Clinical trial NCT00140205: Pharmacokinetics of Leptin Administration During Fasting
Official title: Pharmacokinetics of Leptin Administration During Fasting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Energy Deficiency Due to Short-term Fasting
Keywords: leptin
fasting
pharmacokinetics
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2005-09-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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

Eligibility criteria: 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

Primary outcomes:
measure: Leptin Pharmacokinetic Parameters - TIME(T1/2) DAY 3 / TMAX DAY 3 72-hour Fasting Day 3 Leptin Dose 0.01 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 72-hour Fasting Day 3 Leptin Dose 0.01 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetics Parameters - AUC 72-hour Fasting Day 3 Leptin Dose 0.01 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetic Parameters TIME(T1/2) DAY 3 / TMAX DAY 3 72-hour Fasting Day 3 Leptin Dose 0.1 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 72-hour Fasting Day 3 Leptin Dose 0.1 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetics Parameters - AUC 72-hour Fasting Day 3 Leptin Dose 0.1 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetic Parameters - TIME(T1/2) DAY 3 / TMAX DAY 3 72-hour Fasting Day 3 Leptin Dose 0.3 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 72-hour Fasting Day 3 Leptin Dose 0.3 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetics Parameters - AUC 72-hour Fasting Day 3 Leptin Dose 0.3 mg/kg
timeFrame: 3 DAY
measure: Leptin Pharmacokinetic Parameters - TIME(T1/2) / TMAX 24-hour Fed Leptin Dose 0.3 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 24-hour Fed Leptin Dose 0.3 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetics Parameters - AUC 24-hour Fed Leptin Dose 0.3 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetic Parameters - TIME(T1/2) / TMAX 24-hour Fed Leptin Dose 0.01 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 24-hour Fed Leptin Dose 0.01 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetics Parameters - AUC 24-hour Fed Leptin Dose 0.01 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetic Parameters - TIME(T1/2) / TMAX 24-hour Fed Leptin Dose 0.1 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetics Parameters - c(MAX) / L0 (ENDOGENOUS LEPTIN LEVEL) 24-hour Fed Leptin Dose 0.1 mg/kg
timeFrame: 1 DAY
measure: Leptin Pharmacokinetics Parameters - AUC 24-hour Fed Leptin Dose 0.1 mg/kg
timeFrame: 1 DAY
Secondary outcomes:
measure: Cytokine Levels 24h Fed or 72h Fasting for All Different Leptin Doses (0,01-0,1-0,3 mg/kg)
timeFrame: 1 DAY or DAY 3
measure: Neuroendocrine Hormone Levels 24h Fed or 72h Fasting for All Different Leptin Doses (0,01-0,1-0,3 mg/kg)
timeFrame: 1 DAY or DAY 3
measure: Adipokine Hormone Levels 24h Fed or 72h Fasting for All Different Leptin Doses (0,01-0,1-0,3 mg/kg)
timeFrame: day 3 of fasting and day 1 of fed state
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Christos S Mantzoros, MD DSc FACP FACE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bouzoni E, Perakakis N, Connelly MA, Angelidi AM, Pilitsi E, Farr O, Stefanakis K, Mantzoros CS. PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses. Metabolism. 2022 Sep;134:155265. doi: 10.1016/j.metabol.2022.155265. Epub 2022 Jul 9.
citation: Chrysafi P, Perakakis N, Farr OM, Stefanakis K, Peradze N, Sala-Vila A, Mantzoros CS. Leptin alters energy intake and fat mass but not energy expenditure in lean subjects. Nat Commun. 2020 Oct 13;11(1):5145. doi: 10.1038/s41467-020-18885-9.
citation: Moragianni VA, Aronis KN, Chamberland JP, Mantzoros CS. Short-term energy deprivation alters activin a and follistatin but not inhibin B levels of lean healthy women in a leptin-independent manner. J Clin Endocrinol Metab. 2011 Dec;96(12):3750-8. doi: 10.1210/jc.2011-1453. Epub 2011 Sep 14.
citation: Aronis KN, Diakopoulos KN, Fiorenza CG, Chamberland JP, Mantzoros CS. Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans. Diabetologia. 2011 Sep;54(9):2358-67. doi: 10.1007/s00125-011-2201-x. Epub 2011 Jun 10.
citation: Scheer FA, Chan JL, Fargnoli J, Chamberland J, Arampatzi K, Shea SA, Blackburn GL, Mantzoros CS. Day/night variations of high-molecular-weight adiponectin and lipocalin-2 in healthy men studied under fed and fasted conditions. Diabetologia. 2010 Nov;53(11):2401-5. doi: 10.1007/s00125-010-1869-7. Epub 2010 Aug 12.