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

Sponsor:	Oregon Health and Science University
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00688987

Purpose

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	Intervention
Obesity Addison's Disease	Drug: Hydrocortisone Dietary Supplement: Isocaloric Diet

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Single Blind (Investigator) Primary Purpose: Treatment
Official Title:	Cortisol, Central Obesity, and Insulin Resistance: Long Term Studies in Addison's Patients

Resource links provided by NLM:

Genetics Home Reference related topics: 21-hydroxylase deficiency 3-beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency persistent Müllerian duct syndrome

MedlinePlus related topics: Addison's Disease Diabetes Medicines Obesity

Drug Information available for: Hydrocortisone acetate Hydrocortisone Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone cypionate Cortisol succinate Cortisol 21-phosphate

U.S. FDA Resources

Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy [ Time Frame: After 4-months on each dose ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	August 2000
Study Completion Date:	August 2004
Primary Completion Date:	July 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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. Other Name: hydrocortisone
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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00688987

Locations

United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239

Sponsors and Collaborators

Oregon Health and Science University

More Information

No publications provided

Responsible Party:	Jonathan Q. Purnell, OHSU - The Center for the Study of Weight Regulation
ClinicalTrials.gov Identifier:	NCT00688987 History of Changes
Other Study ID Numbers:	eIRB 545, OCTRI #711
Study First Received:	May 30, 2008
Last Updated:	June 4, 2008
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Addison Disease
Adrenal Hyperplasia, Congenital
Obesity
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Adrenogenital Syndrome
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors

Metabolism, Inborn Errors
Metabolic Diseases
Gonadal Disorders
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012