Secondary Analysis of Gut Hormones and Inflammatory Cytokines in Fasting Subjects

• ClinicalTrials.gov Identifier: NCT01257841
• Recruitment Status: Completed
• First Posted: December 10, 2010
• Last Update Posted: December 10, 2010
• Sponsor: Massachusetts General Hospital
• Collaborator: Massachusetts Institute of Technology
• Information provided by: Massachusetts General Hospital

Study Description

Brief Summary:

The original study executed between 2002-2004 was an interventional trial in which 20, healthy, normal-weight female subjects were randomized to a four-day fast plus daily subcutaneous injections of leptin or a four day fast plus daily subcutaneous injections of a placebo. The primary endpoints were gonadotropin pulsatility, TSH secretion and thyroid function, and cortisol secretion. The current study is a secondary analysis focussed on the placebo group which underwent a four-day fast. The study is looking at the effects of fasting on gut-derived hormones and inflammatory markers in healthy, normal-weight women. The hypothesis for this secondary analysis was that four days of fasting would augment levels of orexigenic gut-derived hormones and suppress levels of anorexigenic gut-derived horomones, while suppressing secretion of inflammatory cytokines.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Leptin administration; Behavioral: Fasting	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Official Title: Effects of Four-day Fast on Gut-derived Hormones and Inflammatory Markers in Healthy, Normal-weight Women.
• Study Start Date: November 2002
• Actual Primary Completion Date: December 2003
• Actual Study Completion Date: December 2003

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Fasting alone	Behavioral: Fasting; Complete fasting, save for water and multivitamin, for four days.
Active Comparator: Fasting plus leptin	Drug: Leptin administration; Leptin 0.05 mg/kg sc daily in divided doses (0800, 1400, 2000, and 0200h) for four days.; Behavioral: Fasting; Complete fasting, save for water and multivitamin, for four days.

Outcome Measures

Primary Outcome Measures :

1. Hormone levels change from baseline. [ Time Frame: Change from baseline after 4 days of intervention. ]
   Original study looking at gonadotropin pulsitility, TSH secretion and thyroid function, and cortisol secretion. Present study looking at gut-hormone secretion.

Secondary Outcome Measures :

1. Levels of inflammatory cytokines change from baseline. [ Time Frame: Change from baseline after 4 days of intervention. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• female age 18-35
• BMI 20-26.0
• eumenorrheic with normal FSH, TSH, Prolactin
• Hgb > 12 g/dL, normal creatinine
• normal puberty and development
• negative pregnancy test. In addition, subjects agreed not to be sexually active during the course of the inpatient study and to use contraception for a period of 48 hours after discharge from the hospital.

Exclusion Criteria:

• medical or endocrine problems known to affect thyroid, reproductive, GH or cortisol function
• medications known to affect neuroendocrine function
• prior history of eating disorder or significant menstrual irregularities
• subjects who have a known hypersensitivity to E. Coli derived protein.
• subjects with a history of seizure disorder, significant cardiac disease, medication for cardiac disease, or kidney disease
• history of anaphylaxis or anaphylactoid like reactions.

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Massachusetts Institute of Technology

Cambridge, Massachusetts, United States, 02139

Sponsors and Collaborators

Massachusetts General Hospital

Massachusetts Institute of Technology

Investigators

• Principal Investigator: Steven K Grinspoon, MD; Massachusetts General Hospital

More Information

Publications of Results:

Canavan B, Salem RO, Schurgin S, Koutkia P, Lipinska I, Laposata M, Grinspoon S. Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation. J Clin Endocrinol Metab. 2005 Oct;90(10):5779-85. Epub 2005 Aug 2.

Schurgin S, Canavan B, Koutkia P, Depaoli AM, Grinspoon S. Endocrine and metabolic effects of physiologic r-metHuLeptin administration during acute caloric deprivation in normal-weight women. J Clin Endocrinol Metab. 2004 Nov;89(11):5402-9.

Koutkia P, Schurgin S, Berry J, Breu J, Lee BS, Klibanski A, Grinspoon S. Reciprocal changes in endogenous ghrelin and growth hormone during fasting in healthy women. Am J Physiol Endocrinol Metab. 2005 Nov;289(5):E814-22. Epub 2005 Jun 21.

• Responsible Party: Steven K Grinspoon, M.D. Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01257841
• Other Study ID Numbers: 2002P-000518SA1
• First Posted: December 10, 2010
• Last Update Posted: December 10, 2010
• Last Verified: December 2010

Keywords provided by Massachusetts General Hospital:

Fasting; Gut hormones; Inflammatory Cytokines