Secondary Analysis of Gut Hormones and Inflammatory Cytokines in Fasting Subjects

Effects of Four-day Fast on Gut-derived Hormones and Inflammatory Markers in Healthy, Normal-weight Women.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Behavioral: Fasting; Drug: Leptin administration

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Cambridge, Massachusetts, United States, 02139
      • Massachusetts Institute of Technology

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Levels of inflammatory cytokines change from baseline.	Change from baseline after 4 days of intervention.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Massachusetts Institute of Technology
• Investigators: Principal Investigator: Steven K Grinspoon, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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. doi: 10.1210/jc.2005-0780. 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. doi: 10.1210/jc.2004-1102.
• 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. doi: 10.1152/ajpendo.00093.2005. Epub 2005 Jun 21.

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (Actual): December 1, 2003
• Study Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: December 7, 2010
• First Submitted That Met QC Criteria: December 9, 2010
• First Posted (Estimate): December 10, 2010

Study Record Updates

• Last Update Posted (Estimate): December 10, 2010
• Last Update Submitted That Met QC Criteria: December 9, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Fasting; Gut hormones; Inflammatory Cytokines
• Other Study ID Numbers: 2002P-000518SA1