Current partner codePEPTIDESDE

Role of Leptin in the Neuroendocrine and Immune Response to Fasting

Status

Completed

Phase

Phase 1 / Phase 2

Enrollment

13

Locations

1

Results

Posted

Publications

7

Study summary

What the protocol is testing.

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.

Full 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

Interventions

Treatment arms and agents.

DRUG

r-metHuLeptin

recombinant human leptin

OTHER

placebo

placebo (no active drug)

Timeline

From registration to results.

  1. First posted

    Sep 1, 2005

  2. Study start

    Oct 2002

  3. Primary completion

    Mar 2011

  4. Study completion

    Dec 2016

  5. Results posted

    Jun 7, 2017

  6. Registry updated

    Jun 7, 2017

Outcomes

What the study measures.

Primary outcomes

Cortisol

Time frame · four days

ACTH Mean Level

Time frame · 4 days

Response of ACTH to leptin administration in fed and fasting state from baseline was measured

Immune Function CD3 Count

Time frame · 4 days

Secondary outcomes

%Fat Mass

Time frame · four days

(RMR)

Time frame · four days

Resting Metabolic rate using calorimetry

Autonomic Function

Time frame · 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

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
30 Years
Sex
ALL
Healthy volunteers
Yes

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 locations

1 registered sites.

United States. Showing up to 24 locations stored in the fast local snapshot.

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Publications

Results and literature.

PMID 12727933Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest. 2003 May;111(9):1409-21. doi: 10.1172/JCI17490.PMID 39097160Stefanakis K, Samiotaki M, Papaevangelou V, Valenzuela-Vallejo L, Giannoukakis N, Mantzoros CS. Longitudinal proteomics of leptin treatment in humans with acute and chronic energy deficiency-induced hypoleptinemia reveal novel, mainly immune-related, pleiotropic effects. Metabolism. 2024 Oct;159:155984. doi: 10.1016/j.metabol.2024.155984. Epub 2024 Aug 2.PMID 35820631Bouzoni 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.PMID 33051459Chrysafi 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.PMID 25540981Foo JP, Aronis KN, Chamberland JP, Mantzoros CS. Lack of Day/Night variation in fibroblast growth factor 21 levels in young healthy men. Int J Obes (Lond). 2015 Jun;39(6):945-8. doi: 10.1038/ijo.2014.215. Epub 2014 Dec 26.PMID 23193213Foo JP, Aronis KN, Chamberland JP, Paruthi J, Moon HS, Mantzoros CS. Fibroblast growth factor 21 levels in young healthy females display day and night variations and are increased in response to short-term energy deprivation through a leptin-independent pathway. Diabetes Care. 2013 Apr;36(4):935-42. doi: 10.2337/dc12-0497. Epub 2012 Nov 27.PMID 21917874Moragianni 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.

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