FastingPhase 1/2NCT00140231
Role of Leptin in the Neuroendocrine and Immune Response to Fasting
A Phase 1/2 study testing r-metHuLeptin in people with Fasting, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Fasting
- What is being tested?
- r-metHuLeptin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2002to Dec 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Role of Leptin in the Neuroendocrine and Immune Response to Fasting in Humans
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.
Read the 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
- Conditions
- Fasting
- Being tested
- r-metHuLeptin, placebo
- Keywords
- leptin, fasting, reproductive, neuroendocrine, immune function, energy deficiency associated with short-term fasting
- Medical subject headings
- Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
r-metHuLeptinDrug
Also called metreleptin
recombinant human leptin
placeboOther
placebo (no active drug)
| Study group | Role | What they receive |
|---|---|---|
| Metreleptin | Active comparator | r-metHuLeptin self-administered subcutaneously Receives: Drug: r-metHuLeptin; Other: placebo |
| Placebo | Placebo comparator | Placebo, administered in same method as active arm. Receives: Drug: r-metHuLeptin; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortisol
Measured: four days
ACTH Mean Level
Response of ACTH to leptin administration in fed and fasting state from baseline was measured
Measured: 4 days
Immune Function CD3 Count
Measured: 4 days
Secondary outcomes (3)
%Fat Mass
Measured: four days
(RMR)
Resting Metabolic rate using calorimetry
Measured: four days
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
Measured: four days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2005 (estimated)
- Study startOct 2002
- Primary completionMar 2011
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for FastingStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR), Amgen
- Responsible party
- Principal investigator, Christos Mantzoros, Beth Israel Deaconess Medical Center
- Investigators
- Christos S Mantzoros, MD, DSc, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00140231
- Sponsor's protocol ID
- 2002P000049
- Other IDs
- 2M01RR001032-30, 5R01DK058785-07
- Status last verified
- May 2017
- First submitted
- 30 Aug 2005
- Last updated
- 7 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 12727933Stefanakis 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.
PubMed 39097160Bouzoni 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.
PubMed 35820631Chrysafi 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.
PubMed 33051459Foo 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.
PubMed 25540981Foo 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.
PubMed 23193213Moragianni 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.
PubMed 21917874
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Leptin in the Neuroendocrine and Immune Response to Fasting in Humans
- ClinicalTrials.gov ID
- NCT00140231
- Acronym / sponsor ID
- 2002P000049
- Conditions
- Fasting
- Keywords
- leptin, fasting, reproductive, neuroendocrine, immune function, energy deficiency associated with short-term fasting
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR), Amgen
- Study start
- Oct 2002
- Primary completion
- Mar 2011 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 1 Sep 2005 (estimated)
- Results
- Posted 7 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metreleptin | Active comparator | Drug: r-metHuLeptin, Other: placebor-metHuLeptin self-administered subcutaneously |
| Placebo | Placebo comparator | Drug: r-metHuLeptin, Other: placeboPlacebo, administered in same method as active arm. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| r-metHuLeptinAlso: metreleptinrecombinant human leptin | Drug | Metreleptin, Placebo |
| placeboplacebo (no active drug) | Other | Metreleptin, Placebo |
Primary outcome
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
3 secondary outcomes
%Fat Mass
Time frame: four days
(RMR)
Time frame: four days
Autonomic Function
Time frame: four days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 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.
- Derived from this study: PubMed 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.
- Derived from this study: PubMed 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.
- Derived from this study: PubMed 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.
- Derived from this study: PubMed 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.
- Derived from this study: PubMed 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.
- Derived from this study: PubMed 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.
- Click here for more information about the Mantzoros Research Group.Link provided by the sponsor.
- Click here for more information about Beth Israel Deaconess Medical Center.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christos S Mantzoros, MD, DSc principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing r-metHuLeptin in people with Fasting, run by Beth Israel Deaconess Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortisol (time frame: four days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00140231, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.