HORMA: Hormonal Regulators of Muscle and Metabolism in Aging - Full Text View

Sponsor:	National Institute on Aging (NIA)
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00183040

Purpose

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.

Condition	Intervention	Phase
Sarcopenia Muscle Weakness Frailty	Drug: Topical testosterone Drug: Recombinant human growth hormone	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Hormonal Regulators of Muscle and Metabolism in Aging

Resource links provided by NLM:

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

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).

Secondary Outcome Measures:

change in skeletal muscle strength, muscle mass, power and fatigability (endurance), physical performance, and markers of safety.

Estimated Enrollment:	108
Study Start Date:	September 2002
Study Completion Date:	February 2007
Primary Completion Date:	February 2007 (Final data collection date for primary outcome measure)

Detailed 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.

Eligibility

Ages Eligible for Study:	65 Years to 90 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00183040

Locations

United States, Massachusetts
Tufts University
Boston, Massachusetts, United States, 02111
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63108

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Fred R. Sattler, MD

Keck School of Medicine, University of Southern California

More Information

Publications:

Dutta C, Hadley EC, Lexell J. Sarcopenia and physical performance in old age: overview. Muscle Nerve Suppl. 1997;5:S5-9. Review. No abstract available.

Hasten DL, Pak-Loduca J, Obert KA, Yarasheski KE. Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. Am J Physiol Endocrinol Metab. 2000 Apr;278(4):E620-6.

Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferrando A. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol. 1995 Nov;269(5 Pt 1):E820-6.

Ferrando AA, Sheffield-Moore M, Yeckel CW, Gilkison C, Jiang J, Achacosa A, Lieberman SA, Tipton K, Wolfe RR, Urban RJ. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E601-7.

Blackman MR, Sorkin JD, Munzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O'Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell E, St Clair C, Pabst KM, Harman SM. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA. 2002 Nov 13;288(18):2282-92.

Study ID Numbers:	AG0045, R01AG18169-01, USC GCRC Protocol #1030
Study First Received:	September 13, 2005
Last Updated:	May 28, 2009
ClinicalTrials.gov Identifier:	NCT00183040 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

andropause
hormone therapy
HRT

Additional relevant MeSH terms:

Neuromuscular Manifestations
Nervous System Diseases
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Muscle Weakness
Hormones
Pharmacologic Actions

Signs and Symptoms
Testosterone
Muscular Diseases
Pathologic Processes
Musculoskeletal Diseases
Neurologic Manifestations
Androgens

ClinicalTrials.gov processed this record on February 08, 2010