The Hypothalamic-Pituitary-Adrenal (HPA) Axis as an Effector System in Weight Regulation

• ClinicalTrials.gov Identifier: NCT00688987
• Recruitment Status: Completed
• First Posted: June 3, 2008
• Last Update Posted: June 5, 2008
• Sponsor: Oregon Health and Science University
• Information provided by: Oregon Health and Science University

Study Description

Brief Summary:

Replacing glucocorticoid in a dose dependent manner (including doses within the physiological range) to subjects with adrenal insufficiency will increase visceral fat accumulation independently of total fat mass.

Condition or disease	Intervention/treatment	Phase
Obesity; Addison's Disease	Drug: Hydrocortisone; Dietary Supplement: Isocaloric Diet	Not Applicable

Detailed Description:

To measure total fat mass by DEXA scan, central (visceral) fat accumulation, insulin sensitivity by FSIVGTT, lipid levels, and adipocyte gene expression in subjects with AI receiving increasing doses of hydrocortisone replacement (15 mg, 25 mg, and 40 mg per day in split doses) for 4-months at a time during ad-lib feeding.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Cortisol, Central Obesity, and Insulin Resistance: Long Term Studies in Addison's Patients
• Study Start Date: August 2000
• Actual Primary Completion Date: July 2004
• Actual Study Completion Date: August 2004

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; Subjects with AI will be randomized to each of three doses of hydrocortisone for 4 months on each dose.	Drug: Hydrocortisone; Subjects will receive in random order daily (split) dosing of hydrocortisone: a low dose of 15 mg (10 in AM, 5 in PM); a medium dose of 25 mg (15 in AM, 10 in PM) and high dose of 40 mg (30 in AM, 10 in PM) for 4 months.
Active Comparator: 2; isocaloric diet	Dietary Supplement: Isocaloric Diet; Subjects will eat an isocaloric diet for 4 weeks while taking hydrocortisone; Other Name: Weight stable diet

Outcome Measures

Primary Outcome Measures :

1. Amounts of intra-abdominal fat and total fat at the end of the treatment period for each cortisol dose. [ Time Frame: After 4 months on each dose ]

Secondary Outcome Measures :

1. Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy [ Time Frame: After 4-months on each dose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects with complete adrenal failure as defined as spontaneous serum cortisol of levels less than 5 g/dl after 12 hours without glucocorticoid replacement and peak serum cortisol of < 5 g/dl 60 minutes after a 250 g ACTH stimulation test.
• Subjects who are at their usual weight (weight stable for at least 1 year)
• Subjects on stable replacement doses of any required hormone such as thyroid, sex hormones, mineralocorticoid replacement, growth hormone, and hydrocortisone for at least 6 months, and 4) have a normal body weight (BMI 19-27 kg/m2).

Exclusion Criteria:

• Possible confounders on body weight and insulin resistance
• Age less than 18 to exclude those who might be experiencing alterations in cortisol production or weight as a result of adolescent growth.
• Subjects who exercise > 30 minutes/day, 3 times a week.
• Smokers.
• Heavy alcohol drinkers (> 2 drinks/ day).
• Subjects with medical diagnosis including diabetes, heart disease, and cancer.
• Subjects with psychiatric illness (i.e., depression, psychosis, bipolar, schizophrenia; or are taking medications for these disorders).

Contacts and Locations

Locations

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

Sponsors and Collaborators

Oregon Health and Science University

More Information

• Responsible Party: Jonathan Q. Purnell, OHSU - The Center for the Study of Weight Regulation
• ClinicalTrials.gov Identifier: NCT00688987
• Other Study ID Numbers: eIRB 545; OCTRI #711
• First Posted: June 3, 2008
• Last Update Posted: June 5, 2008
• Last Verified: June 2008

Additional relevant MeSH terms:

Obesity; Addison Disease; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Signs and Symptoms; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hydrocortisone; Anti-Inflammatory Agents