Topical testosterone and Recombinant human growth hormone in Muscle Weakness and Frailty and Sarcopenia - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

108

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 90 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Factorial Assignment
Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute on Aging (NIA)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2002

Primary Completion (Actual)

February 1, 2007

Study Completion (Actual)

February 1, 2007

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria