DHEA and Testosterone Replacement in Elderly

Overview[ - collapse ][ - ]

Purpose 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.
ConditionAging
Low DHEA for Women
Low Testosterone and DHEA for Men
InterventionProcedure: Androgen Replacement
PhaseN/A
SponsorMayo Clinic
Responsible PartyMayo Clinic
ClinicalTrials.gov IdentifierNCT00254371
First ReceivedNovember 14, 2005
Last UpdatedMay 20, 2011
Last verifiedMay 2011

Tracking Information[ + expand ][ + ]

First Received DateNovember 14, 2005
Last Updated DateMay 20, 2011
Start DateJuly 1998
Estimated Primary Completion DateFebruary 2007
Current Primary Outcome Measures
  • physical performance (VO2 peak, muscle strength as measured by chest press, double knee extension, and isokinetic knee extension
  • body composition (fat percent, fat free mass, abdominal visceral fat, and thigh muscle area)
  • bone parameters (BMD of ultradistal radius, femur neck, femur total and anterior-posterior of L2-L4 spine
  • fasting plasma insulin and glucose
Current Secondary Outcome Measures
  • quality of life
  • glucose and insulin after mixed meal
  • muscle protein synthesis
  • hormone levels
  • prostate size

Descriptive Information[ + expand ][ + ]

Brief TitleDHEA and Testosterone Replacement in Elderly
Official TitlePathogenesis of Sarcopenia and Metabolic Changes in Aging
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhaseN/A
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Condition
  • Aging
  • Low DHEA for Women
  • Low Testosterone and DHEA for Men
InterventionProcedure: Androgen Replacement
Study Arm (s)Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment150
Estimated Completion DateFebruary 2007
Estimated Primary Completion DateFebruary 2007
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.
GenderBoth
Ages60 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00254371
Other Study ID Numbers547-96
Has Data Monitoring CommitteeNot Provided
Information Provided ByMayo Clinic
Study SponsorMayo Clinic
CollaboratorsNational Institute on Aging (NIA)
National Institutes of Health (NIH)
Investigators Principal Investigator: K. Sreekumaran Nair, M.D., Ph.D. Mayo Clinic
Verification DateMay 2011

Locations[ + expand ][ + ]

Mayo Clinic
Rochester, Minnesota, United States, 55905