HORMA: Hormonal Regulators of Muscle and Metabolism in Aging

National Institutes of Health (NIH)

Status and phase

Completed

Phase 2

Conditions

Muscle Weakness

Frailty

Sarcopenia

Treatments

Drug: Recombinant human growth hormone

Drug: Topical testosterone

Study type

Interventional

Funder types

NIH

Identifiers

NCT00183040

USC GCRC Protocol #1030

R01AG018169-01 (U.S. NIH Grant/Contract)

AG0045

Details and patient eligibility

About

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.

Full description

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.

Enrollment

108 estimated patients

Sex

Male

Ages

65 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Men who are 65-90 years of age
Total serum IGF-1 (insulin-like growth factor) in the lower tertile for adults (56-167 ug/dl)
Total serum testosterone of 150-550 ng/dL

Exclusion criteria

BMI (Body Mass Index) 35 kg/m2 or greater
Weight instability (>3% change in prior 3 months)
Daily intake of total kilocalories less than or equal to 0.8X the RDA and intake of protein between 0.8 and 1.4 g/kg/day inclusive
Acute illness in the prior 30 days
Resistance training (wt lifting) in the past 12 months
Vigorous aerobic sports (Competing as a Master athlete in the prior 5 years; weekly swimming, racquet ball, cycling, tennis, in preceding 12 months)
Use of an anabolic agent (androgen, androgen precursor, rhGH, etc) in the preceding 12 months
Use of medications that might affect amino acid metabolism (e.g. beta-adrenergic blockers, beta-agonists, Ca2+ channel blockers, corticosteroids)
Fasting sugar greater than or equal to 126 mg/dl or diabetes requiring Rx
History of benign intracranial hypertension
Heart failure, active angina, or myocardial infarction in the prior 6 months or history of aortic stenosis
Uncontrolled hypothyroidism or hyperthyroidism
Rheumatoid arthritis, cirrhosis or active hepatitis
History of carpal tunnel syndrome
Prior cancer other than squamous or basal cell carcinoma of the skin
Sleep apnea or severe chronic lung disease
Anticoagulation with heparin or coumadin
Blood pressure not controlled with medication to <180/95 mm Hg
Calculated creatinine clearance <50 cc/min
Serum prostatic antigen >4.0 or American Urological Association score greater than or equal to 8
Hematocrit greater than or equal 52%, or ALT >1.5X ULN
Failure to pass a modified Bruce treadmill stress test
Severe disability limiting strength or physical function testing
Dementia or cognitive impairment affecting a subject's ability to provide informed consent