Clinical trial NCT00254371: DHEA and Testosterone Replacement in Elderly
Official title: Pathogenesis of Sarcopenia and Metabolic Changes in Aging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aging
Low DHEA for Women
Low Testosterone and DHEA for Men
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: National Institutes of Health (NIH)
First posted: 2005-11-16
Enrollment: 150
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sarcopenia is a major health problem among the rapidly expanding elderly population in our society. Disabilities directly related to muscle weakness, and indirectly related to changes in body composition and metabolic dysfunctions, are causing a staggering toll in disability and health care costs.

Osteopenia occurs almost simultaneously with sarcopenia in the elderly population and muscle weakness increases the risk for falls and therefore, fractures. Although these issues have been separate addressed in several studies, an integrated investigational approach to better understand the pathogenesis of sarcopenia and other age-related metabolic abnormalities and to investigate the potential role of androgens have not been undertaken in a comprehensive manner.

The program contains four independent research programs, each representing different research disciplines, and four separate cores supporting the four projects.

The main focus of the project is to determine the effect of the replacement of testosterone in elderly men and DHEA in elderly men and women and to compare these effects with placebo treatment over a two-year period.

Project 1, "Effect of Androgen Replacement on Muscle Metabolism" will specifically determine whether these interventions have a differential effect on size and quality of muscle in terms of strength and metabolic functions. Project 2, "Effect of Androgen Replacement on Bone Metabolism," will determine the effects of this intervention on bone mineral density and markers of bone turnover.

Project 3, "The Effect of Androgen Replacement on Carbohydrate Metabolism," will determine whether the age-associated decrease in circulating androgens contributes to the alterations in carbohydrate metabolism that are commonly observed in the elderly and on insulin action, insulin secretion, and glucose effectiveness.

Project 4, "Effect of Androgen Replacement on Fat Metabolism" will determine whether changes in fat distribution that occur with aging could result from differences in regional fatty acid uptake and systemic fatty acid kinetics, and whether these determinants of fat distribution are altered by the interventions.

The data emerging from these studies will be integrated to determine the intervention of sarcopenia with other metabolic changes and hopefully will contribute to a better understanding of muscle, bone, carbohydrate and fat metabolism.

This study will hopefully form the scientific basis for future trials of androgen replacement in the elderly.


Eligibility criteria: Inclusion criteria:

bioavailable testosterone less than 103 nanogram/dl and DHEA-S level less than 157 microgram/dl for men; DHEA-S less than 95 microgram/dl for women;

Exclusion criteria:

significant ischemic heart disease, renal disease, uncontrolled hypertension, diabetes mellitus, malignancy, malabsorption, bone disorders, chronic obstructive pulmonary disease, or sleep apnea.

Others exclusion criteria include abnormal serum calcium, phosphorus, alkaline phosphatase, asparate aminotransferase, creatinine, urinary calcium, thyroid stimulating hormone, and erythrocyte sedimentation rate.

People taking medication that may affect outcome measures such as adrenal steroids, anticonvulsant therapy thiazide diuretics, and estrogen replacement were also excluded. People engaged in a regular exercise program lasting more than 20 minutes more than two times per week and those men whose PSA level (age adjusted upper limit) were also excluded.

Primary outcomes:
measure: physical performance (VO2 peak, muscle strength as measured by chest press, double knee extension, and isokinetic knee extension
measure: body composition (fat percent, fat free mass, abdominal visceral fat, and thigh muscle area)
measure: bone parameters (BMD of ultradistal radius, femur neck, femur total and anterior-posterior of L2-L4 spine
measure: fasting plasma insulin and glucose
Secondary outcomes:
measure: quality of life
measure: glucose and insulin after mixed meal
measure: muscle protein synthesis
measure: hormone levels
measure: prostate size
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: K. Sreekumaran Nair, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ 3rd, Smith GE, Khosla S, Jensen MD. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006 Oct 19;355(16):1647-59. doi: 10.1056/NEJMoa054629.
citation: Espinosa De Ycaza AE, Rizza RA, Nair KS, Jensen MD. Effect of Dehydroepiandrosterone and Testosterone Supplementation on Systemic Lipolysis. J Clin Endocrinol Metab. 2016 Apr;101(4):1719-28. doi: 10.1210/jc.2015-4062. Epub 2016 Feb 17.
citation: Bush NC, Basu R, Rizza RA, Nair KS, Khosla S, Jensen MD. Insulin-mediated FFA suppression is associated with triglyceridemia and insulin sensitivity independent of adiposity. J Clin Endocrinol Metab. 2012 Nov;97(11):4130-8. doi: 10.1210/jc.2012-2285. Epub 2012 Aug 29.
citation: Srinivasan M, Irving BA, Frye RL, O'Brien P, Hartman SJ, McConnell JP, Nair KS. Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly men and women and testosterone in elderly men. J Clin Endocrinol Metab. 2010 Apr;95(4):1617-25. doi: 10.1210/jc.2009-2000. Epub 2010 Feb 5.