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| ID | Type | Description | Link |
|---|---|---|---|
| 2M01RR001032-30 | U.S. NIH Grant/Contract | View source | |
| 5R01DK058785-07 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| National Center for Research Resources (NCRR) | NIH |
| Amgen | INDUSTRY |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metreleptin | Active Comparator | r-metHuLeptin self-administered subcutaneously |
|
| Placebo | Placebo Comparator | Placebo, administered in same method as active arm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| r-metHuLeptin | Drug | recombinant human leptin |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| %Fat Mass | four days | |
| (RMR) | Resting Metabolic rate using calorimetry | four days |
| Autonomic Function |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christos S Mantzoros, MD, DSc | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12727933 | Background | Chan 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. | |
| 39097160 | Derived | Stefanakis 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. |
| Label | URL |
|---|---|
| Click here for more information about the Mantzoros Research Group. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Iso Fed, Then Fasting w/ Metreleptin, Then Fasting w/ Placebo | Six young, healthy, and lean women (age, 22.8,; BMI,21.7kg/m2) who were eumenor- rheic were enrolled in a clinical researchcenter- based, randomized, cross-over interventional study involving three separate 5-day-long inpatient admissions (22). Six subjects with a cross-over design, enabling paired comparisons, would provide 80% power to detect a difference of 1.4 SD between different conditionsat the conventional a=0.05 level. In thefirst admission, the subjects were studied in the isocaloric fed state, whereas in the following two admissions the subjects were studied in the prolonged fasting state for 72 h and were randomized to receive either placebo or metreleptin at replacement doses. A cross-over to the opposite arm took place in the later admission so that all six subjects received both placebo and metreleptin. r-metHuLeptin self-administered subcutaneously r-metHuLeptin: recombinant human leptin |
| FG001 | Iso Fed, Then Fasting w/ Placebo, Then Fasting w/ Met | Placebo, administered in same method as active arm. placebo: placebo (no active drug) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fed State 1 Day- day5 |
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| Washout 8weeks |
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| First Fasting State 3 Days With Placebo |
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| Washout 8 Weeks |
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| Fasting State With Leptin and Crossover |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Iso Fed, Then Fasting w/ Metreleptin, Then Fasting w/ Placebo | r-metHuLeptin self-administered subcutaneously r-metHuLeptin: recombinant human leptin |
| BG001 | Iso Fed, Then Fasting w/ Placebo, Then Fasting w/ Metreleptin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cortisol | Posted | Mean | Standard Deviation | ug/dl | four days |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metreleptin | r-metHuLeptin self-administered subcutaneously r-metHuLeptin: recombinant human leptin |
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Our study is confined to lean, healthy female subjects; therefore, our results should not be generalized to male, obese,or diabetic subjects
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christos Mantzoros | BIDMC | 6176678633 | cmantzor@bidmc.harvard.edu |
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| ID | Term |
|---|---|
| D005215 | Fasting |
| ID | Term |
|---|---|
| D005247 | Feeding Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| C122136 | recombinant methionyl human leptin |
| C415771 | metreleptin |
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| placebo | Other | placebo (no active drug) |
|
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 |
| 35820631 | Derived | 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. |
| 33051459 | Derived | 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. |
| 25540981 | Derived | Foo 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. |
| 23193213 | Derived | Foo 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. |
| 21917874 | Derived | 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. |
| Click here for more information about Beth Israel Deaconess Medical Center. | View source |
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Placebo, administered in same method as active arm.
placebo: placebo (no active drug)
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
|
| Primary | ACTH Mean Level | Response of ACTH to leptin administration in fed and fasting state from baseline was measured | Posted | Mean | Standard Error | pg/ml | 4 days |
|
|
|
| Primary | Immune Function CD3 Count | Posted | Mean | Standard Error | cells/ul | 4 days |
|
|
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| Secondary | %Fat Mass | Posted | Mean | Standard Deviation | fat% | four days |
|
|
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| Secondary | (RMR) | Resting Metabolic rate using calorimetry | Posted | Mean | Standard Deviation | kcal/d | four days |
|
|
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| Secondary | 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 | Posted | Mean | Standard Error | pg/ml | four days |
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|
| 0 |
| 13 |
| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Placebo | Placebo, administered in same method as active arm. placebo: placebo (no active drug) | 0 | 13 | 0 | 13 | 0 | 13 |
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