Clinical trial NCT00279929: DHEA Replacement in Adrenalectomized/Hypoadrenal Patients
Official title: Assessing the Effects of Dehydroepiandrosterone Replacement on the Mood of Adrenalectomised/Hypoadrenal Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aging
Dehydroepiandosterone Replacement
DHEA Replacement
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Aging (NIA)
First posted: 2006-01-20
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The role of dehydroepiandosterone (DHEA) and its sulphated ester (DHEAS) \[together known as DHEA(S)\] in humans remains to be fully elucidated. They are the most abundant circulating steroid hormones in humans with the principle source of production being the adrenal glands. In adrenalectomised or hypoadrenal subjects it is not standard clinical practice to replace this hormone. Whilst this lack of DHEA(S) is clearly not life threatening, the published literature on the psychological effects of replacement in this population has shown some benefit in quality of life but data concerning the metabolic effects is conflicting and incomplete. We wish to carry out a study to measure the effect of DHEA(S) replacement in a group of adrenalectomised / hypoadrenal subjects and measure the outcome of a number of psychological and metabolic parameters both prior to and after twelve weeks of 50 mg/day DHEA(S) in a double blind randomised cross over design.

Mood, quality of life and sexual well being will be assessed using validated questionnaires. In addition, we will utilise the GCRC facility to measure body composition using total body water and DEXA. We will measure insulin sensitivity, exercise performance, muscle fatigability and VO2 max. Pre- and post- intervention muscle biopsies will assess DHEA(S) effects on myosin heavy chain isoform expression; skeletal muscle mitochondrial ATP production and be used to assess muscle enzyme levels.


Eligibility criteria: Inclusion criteria:

* Subjects who have been adrenalectomised or have been hypoadrenal (from whatever cause) for \> 24 months;
* Subjects who have been on a steady glucocorticoid replacement regime for \>12 months;
* Women of child bearing age in whom oestrogen status has been steady for \> 6 months - i.e. either on or off the oral contraceptive pill for that time;
* Subjects on other forms of hormone replacement therapy (e.g. thyroxin) in whom dose has remained the same for \> 6 months.

Exclusion criteria:

* BMI \>35 Kg/m2;
* Individuals with fasting blood glucose above 120mg/dl;
* A history of sex hormone dependant malignancy;
* A history of liver disease;
* Renal failure;
* Cardiovascular disease (other than hypertension);
* Polycythaemia;
* Pregnancy or breastfeeding;
* Cerebrovascular disorders;
* Neurological disorders;
* PSA levels above the age related reference range;
* Use of drugs known to alter mood within the 6 months prior to enrolment;
* Any drug known to affect hepatic biotransformation;
* Evidence of psychiatric disease or dementia;
* Postmenopausal women who have been on hormone replacement therapy for less than six months.

Primary outcomes:
measure: physical performance (VO2 peak, muscle strength as measured by chest press, double knee extension, and isokinetic knee extension
measure: quality of life
measure: glucose and insulin metabolism
measure: muscle protein synthesis
measure: body composition
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: K. Sreekumaran Nair, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dhatariya KK, Greenlund LJ, Bigelow ML, Thapa P, Oberg AL, Ford GC, Schimke JM, Nair KS. Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function. Mayo Clin Proc. 2008 Nov;83(11):1218-25. doi: 10.4065/83.11.1218.