The Hypothalamic-Pituitary-Adrenal (HPA) Axis as an Effector System in Weight Regulation
Primary Purpose
Obesity, Addison's Disease
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hydrocortisone
Isocaloric Diet
Sponsored by
About this trial
This is an interventional treatment trial for Obesity
Eligibility 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).
Sites / Locations
- Oregon Health & Science University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
1
2
Arm Description
Subjects with AI will be randomized to each of three doses of hydrocortisone for 4 months on each dose.
isocaloric diet
Outcomes
Primary Outcome Measures
Amounts of intra-abdominal fat and total fat at the end of the treatment period for each cortisol dose.
Secondary Outcome Measures
Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy
Full Information
NCT ID
NCT00688987
First Posted
May 30, 2008
Last Updated
June 4, 2008
Sponsor
Oregon Health and Science University
1. Study Identification
Unique Protocol Identification Number
NCT00688987
Brief Title
The Hypothalamic-Pituitary-Adrenal (HPA) Axis as an Effector System in Weight Regulation
Official Title
Cortisol, Central Obesity, and Insulin Resistance: Long Term Studies in Addison's Patients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2008
Overall Recruitment Status
Completed
Study Start Date
August 2000 (undefined)
Primary Completion Date
July 2004 (Actual)
Study Completion Date
August 2004 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Oregon Health and Science University
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Addison's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Subjects with AI will be randomized to each of three doses of hydrocortisone for 4 months on each dose.
Arm Title
2
Arm Type
Active Comparator
Arm Description
isocaloric diet
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Isocaloric Diet
Other Intervention Name(s)
Weight stable diet
Intervention Description
Subjects will eat an isocaloric diet for 4 weeks while taking hydrocortisone
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Fasting Lipid levels, fat mass by DEXA, post-heparin lipase activity, insulin sensitivity, and fat biopsy
Time Frame
After 4-months on each dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Facility Information:
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
12. IPD Sharing Statement
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The Hypothalamic-Pituitary-Adrenal (HPA) Axis as an Effector System in Weight Regulation
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