HORMA: Hormonal Regulators of Muscle and Metabolism in Aging

This study has been completed.
Sponsor:
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00183040
First received: September 13, 2005
Last updated: May 28, 2009
Last verified: May 2009
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Hormonal Regulators of Muscle and Metabolism in Aging

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: Fred R. Sattler, MD Keck School of Medicine, University of Southern California
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00183040     History of Changes
Other Study ID Numbers: AG0045, R01AG18169-01, USC GCRC Protocol #1030
Study First Received: September 13, 2005
Last Updated: May 28, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute on Aging (NIA):
andropause
hormone therapy
HRT

Additional relevant MeSH terms:
Asthenia
Muscle Weakness
Paresis
Sarcopenia
Signs and Symptoms
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Muscular Atrophy
Atrophy
Pathological Conditions, Anatomical
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Hormones
Androgens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on August 18, 2014