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

Oregon Health & Science University (OHSU)

Status: Completed

Conditions: Addison's Disease; Obesity

Treatments: Drug: Hydrocortisone; Dietary Supplement: Isocaloric Diet

Study type: Interventional

Funder types: Other

Identifiers

NCT00688987

eIRB 545

OCTRI #711

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

24 participants in 2 patient groups

1

Active Comparator group

Description:

Subjects with AI will be randomized to each of three doses of hydrocortisone for 4 months on each dose.

Treatment:

Drug: Hydrocortisone

2

Active Comparator group

Description:

isocaloric diet

Treatment:

Dietary Supplement: Isocaloric Diet