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

Not Applicable

Completed

• Conditions: Obesity; Addison's Disease
• Interventions: Dietary Supplement: Isocaloric Diet; Drug: Hydrocortisone

• Registration Number: NCT00688987
• Lead Sponsor: Oregon Health and Science University

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.

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 Timeline

• Study Start: 2000-08
• Primary Completion: 2004-07
• Study Completion: 2004-08
• Study First Submitted: 2008-05-30
• Study First Submitted QC: 2008-05-30
• Status Verified: 2008-06
• Study First Posted: 2008-06-03
• Last Update Submitted: 2008-06-04
• Last Update Posted: 2008-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Isocaloric Diet	isocaloric diet
1	Hydrocortisone	Subjects with AI will be randomized to each of three doses of hydrocortisone for 4 months on each dose.

Primary Outcome Measures

Name	Time	Method
Amounts of intra-abdominal fat and total fat at the end of the treatment period for each cortisol dose.	After 4 months on each dose

Secondary Outcome Measures

Name	Time	Method
Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy	After 4-months on each dose

Trial Locations

Locations (1)

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States