TOM: Testosterone in Older Men With Sarcopenia

• ClinicalTrials.gov Identifier: NCT00240981
• Recruitment Status: Terminated
• First Posted: October 18, 2005
• Results First Posted: February 23, 2017
• Last Update Posted: February 23, 2017
• Sponsor: Boston Medical Center
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Shalender Bhasin, Boston Medical Center

Study Description

Brief Summary:

The purpose of this study is to determine whether testosterone replacement in older men with low testosterone levels will increase muscle strength, improve physical performance and overall sense of well being, and reduce fatigue.

Condition or disease	Intervention/treatment	Phase
Sarcopenia; Hypogonadism; Muscular Diseases	Drug: Topical testosterone gel 1% (active formulation); Drug: Topical gel (placebo formulation)	Phase 4

Detailed Description:

The primary objective of this study is to determine whether testosterone replacement in older men, who have low testosterone levels and mild to moderate physical impairment, will increase their maximal voluntary muscle strength of major upper and lower extremity muscle groups. The second objective is to determine whether testosterone replacement will improve the power of knee extension, physical performance tests, the level of physical activity (measured by 3D accelerometer), self-reported disability, exercise tolerance and mobility. The third objective is to determine whether testosterone supplementation improves fatigue, affect, and overall sense of well being in older men with low testosterone levels. A fourth objective is to define the Minimum Clinically Important Differences in physical measures perceived by the participants (MCID).

Participant involvement will require 15-17 clinic visits over 28 weeks. Five to 7 of these visits are for physical testing, including body composition, muscle performance, and physical function. Throughout the study, hormone measurements will be obtained.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 209 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Testosterone Replacement for Older Men With Sarcopenia
• Study Start Date: January 2005
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment	Drug: Topical testosterone gel 1% (active formulation); Starting dose 10 g/day; increased to 15 g/day or decreased to 5 g/day in order to attain morning total testosterone level between 500 - 1000 ng/dL. Blinding achieved by combining a total of 3 tubes of active or placebo gel, applied to upper arms and shoulders each day.; Other Name: Testim®
Placebo Comparator: Placebo	Drug: Topical gel (placebo formulation); Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.

Outcome Measures

Primary Outcome Measures :

1. Changes in Physical Performance Measured by an Exercise Testing Regimen [ Time Frame: baseline and 6 months ]
   Primary outcome was a change from baseline in leg-press strength at 6 months.

Secondary Outcome Measures :

1. Chest-Press [ Time Frame: baseline and 6 months ]
   Change from baseline in chest press strength at 6 months
2. Stair-climbing Test (Without a Load) [ Time Frame: baseline and 6 month ]
   Change from baseline in the stair-climbing test (without a load) at 6 months.
3. Grip Strength [ Time Frame: baseline and 6 months ]
   Change from baseline in grip strength in the dominant hand.
4. 50-Meter Walking Speed (Without a Load) [ Time Frame: baseline and 6 months ]
   Change from baseline 50-Meter Walking Speed (without a load) at 6 months
5. Stair-climbing Test (Loaded) [ Time Frame: baseline and 6 months ]
   Change from baseline in Stair-climbing Test (loaded)
6. Late Life Functional Disability Index (LLFDI) [ Time Frame: baseline and 6 months ]
   Percent change from baseline in the late life functional disability index at 6 months
7. Total Lean Mass [ Time Frame: baseline, 3 months, and 6 months ]
8. Total Fat Mass [ Time Frame: baseline, 3 months, and 6 months ]
9. 50-Meter Walking Speed (With a Load) [ Time Frame: baseline and 6 months ]
   Change from baseline 50-Meter Walking Speed (with a load) at 6 months

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Community dwelling, ages 65 and older
• Self-reported difficulty in climbing 10 steps without resting, or difficulty in walking 2 or 3 blocks outside on level ground
• A score of 4 to 9 on the Short Physical Performance Battery (mild to moderate physical impairment)
• Total serum testosterone level (TT) < 350 ng/dL and > 100 ng/dL
• Without dementia (Mini-Mental State Examination [MMSE] score > 24)

Exclusion Criteria:

• Use of testosterone, anabolic steroids, dehydroepiandrosterone (DHEA), androstenedione or recombinant growth hormone (rGH) in the past year
• Alcohol or drug abuse
• Use of anti-convulsants or glucocorticoids (equivalent to prednisone > 20 mg/day)
• Prostate cancer, breast cancer or other cancers with life expectancy < 5 years
• Limiting neuromuscular, joint or bone disease, or history of stroke with residual neurological problems

• Any neurological condition that would impact cognitive functioning including:

  • epilepsy
  • multiple sclerosis
  • HIV
  • Parkinson's disease
  • stroke
  • other focal lesion
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I psychiatric disorder in past year or use of psychotropic medications in 6 months
• Abnormal prostate examination; PSA > 4 ng/mL; or BPH symptom score > 21
• Unstable angina, New York (NY) class III or IV congestive heart failure or myocardial infarction within 3 months of entry
• Abnormal laboratory values (at discretion of principal investigator)
• Untreated thyroid disease; systolic blood pressure > 160 or diastolic > 100 mm Hg
• Body mass index > 40 kg/m2
• Untreated severe obstructive sleep apnea

Contacts and Locations

Locations

United States, Massachusetts

Boston University Medical Center

Boston, Massachusetts, United States, 02118

VA Boston Healthcare System (Jamaica Plain Campus)

Boston, Massachusetts, United States, 02130

Sponsors and Collaborators

Boston Medical Center

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Shalender Bhasin, MD; Boston University Medical Center, Section of Endocrinology, Diabetes, and Nutrition
• Study Director: Shehzad Basaria, MD; Boston University Medical Center, Section of Endocrinology, Diabetes, and Nutrition
• Principal Investigator: Wildon Farwell, MD, MPH; VA Boston Healthcare System (Jamaica Plain Campus)

More Information

Publications of Results:

Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22. doi: 10.1056/NEJMoa1000485. Epub 2010 Jun 30.

Other Publications:

Hughes VA, Frontera WR, Roubenoff R, Evans WJ, Singh MA. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr. 2002 Aug;76(2):473-81.

Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, Fiatarone Singh MA. Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol A Biol Sci Med Sci. 2001 May;56(5):B209-17.

Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001 Feb;86(2):724-31.

Gray A, Berlin JA, McKinlay JB, Longcope C. An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J Clin Epidemiol. 1991;44(7):671-84.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Traustadóttir T, Harman SM, Tsitouras P, Pencina KM, Li Z, Travison TG, Eder R, Miciek R, McKinnon J, Woodbury E, Basaria S, Bhasin S, Storer TW. Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2861-2869. doi: 10.1210/jc.2017-01902.

Bhasin S, Travison TG, O'Brien L, MacKrell J, Krishnan V, Ouyang H, Pencina K, Basaria S. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Andrology. 2018 Jan;6(1):151-157. doi: 10.1111/andr.12428. Epub 2017 Oct 5.

Gagliano-Jucá T, Storer TW, Pencina KM, Travison TG, Li Z, Huang G, Hettwer S, Dahinden P, Bhasin S, Basaria S. Testosterone does not affect agrin cleavage in mobility-limited older men despite improvement in physical function. Andrology. 2018 Jan;6(1):29-36. doi: 10.1111/andr.12424. Epub 2017 Sep 26.

Huang G, Bhasin S, Tang ER, Aakil A, Anderson SW, Jara H, Davda M, Travison TG, Basaria S. Effect of testosterone administration on liver fat in older men with mobility limitation: results from a randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2013 Aug;68(8):954-9. doi: 10.1093/gerona/gls259. Epub 2013 Jan 4.

Travison TG, Basaria S, Storer TW, Jette AM, Miciek R, Farwell WR, Choong K, Lakshman K, Mazer NA, Coviello AD, Knapp PE, Ulloor J, Zhang A, Brooks B, Nguyen AH, Eder R, LeBrasseur N, Elmi A, Appleman E, Hede-Brierley L, Bhasin G, Bhatia A, Lazzari A, Davis S, Ni P, Collins L, Bhasin S. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2011 Oct;66(10):1090-9. doi: 10.1093/gerona/glr100. Epub 2011 Jun 22.

LeBrasseur NK, Lajevardi N, Miciek R, Mazer N, Storer TW, Bhasin S. Effects of testosterone therapy on muscle performance and physical function in older men with mobility limitations (The TOM Trial): design and methods. Contemp Clin Trials. 2009 Mar;30(2):133-40. doi: 10.1016/j.cct.2008.10.005. Epub 2008 Oct 29.

• Responsible Party: Shalender Bhasin, Professor of Medicine, Boston Medical Center
• ClinicalTrials.gov Identifier: NCT00240981
• Other Study ID Numbers: AG0057; U01AG014369 ( U.S. NIH Grant/Contract )
• First Posted: October 18, 2005
• Results First Posted: February 23, 2017
• Last Update Posted: February 23, 2017
• Last Verified: February 2017

Keywords provided by Shalender Bhasin, Boston Medical Center:

Andropause; frailty; hormone replacement therapy; Aging

Additional relevant MeSH terms:

Muscular Diseases; Sarcopenia; Hypogonadism; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Gonadal Disorders; Endocrine System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs