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

Obesity Clinical Trial

Official title:

Cortisol, Central Obesity, and Insulin Resistance: Long Term Studies in Addison's Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00688987
• Other study ID #: eIRB 545
• Secondary ID: OCTRI #711
• Status: Completed
• Phase: N/A
• First received: May 30, 2008
• Last updated: June 4, 2008
• Start date: August 2000
• Est. completion date: August 2004

Study information

• Verified date: June 2008
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2004
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Addison Disease
• Addison's Disease
• Obesity

Intervention

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.

Dietary Supplement:
• Isocaloric Diet
Subjects will eat an isocaloric diet for 4 weeks while taking hydrocortisone

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy		After 4-months on each dose	No