HORMA: Hormonal Regulators of Muscle and Metabolism in Aging
The purpose of this study is to determine the relationship of deficiencies in testosterone and growth hormone to loss of muscle mass (sarcopenia) and functional impairment during aging and whether there is an interaction of these two hormone systems in maintaining normal skeletal muscle mass and physical function.
Drug: Topical testosterone
Drug: Recombinant human growth hormone
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Factorial Assignment
Primary Purpose: Treatment
|Official Title:||Hormonal Regulators of Muscle and Metabolism in Aging|
- measures of fractional synthetic rates of mixed and contractile (actin and myosin heavy chain [MHC]) skeletal muscle proteins and degradation of skeletal muscle (ubiquitin, and proteasome sub-units)
- analysis of local regulators of skeletal muscle synthesis (e.g. IGF-1, IGFBP4, myostatin).
- change in skeletal muscle strength, muscle mass, power and fatigability (endurance), physical performance, and markers of safety.
|Study Start Date:||September 2002|
|Study Completion Date:||February 2007|
|Primary Completion Date:||February 2007 (Final data collection date for primary outcome measure)|
Elderly persons experience progressive loss of skeletal muscle mass, muscle strength, and functional capacity for activities of daily living. Aging is also associated with a loss of hormones believed to be related to muscle and strength, namely testosterone and growth hormone (GH). The hypothesis being tested is that both hormone systems regulate musculoskeletal protein mass and contractile fibers by different and complimentary mechanisms and that optimal levels of both testosterone and GH are necessary to maintain skeletal muscle mass, muscular strength and power, and full functional activities of daily living during the aging process.
This is a controlled, 16 week study to evaluate the independent effects and interaction of these two anabolic hormone systems in community dwelling elderly men 65-90 years of age who are hyposomatotropic (deficiency of growth hormone) with low eugonadal status (total testosterone of 150-550 ng/dL). The study will utilize a two tiered randomization in which 108 study participants will first be randomized to either the low or high eugonadal level of testosterone using a novel Leydig cell clamp method (GnRH (gonadotropin-releasing hormone) agonist plus topical testosterone supplementation) to achieve target levels of testosterone. Low gonadal status (150-550 ng/dL) will be maintained with 5 g daily doses of topical testosterone, whereas high gonadal status (650-950 ng/dL) will be achieved with 10 g daily doses. Within these two groups, participants will be randomized to receive placebo or one of two doses of rhGH (recombinant human growth hormone) therapy (0, 3.0, 5.0 mcg/kg/day) in a double blinded fashion.
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02111|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63108|
|Principal Investigator:||Fred R. Sattler, MD||Keck School of Medicine, University of Southern California|