TOM: Testosterone in Older Men With Sarcopenia

NCT ID: NCT00240981

Last Updated: 2017-02-23

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

209 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2009-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sarcopenia Hypogonadism Muscular Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Treatment

Group Type EXPERIMENTAL

Topical testosterone gel 1% (active formulation)

Intervention Type DRUG

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.

Placebo

Group Type PLACEBO_COMPARATOR

Topical gel (placebo formulation)

Intervention Type DRUG

Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.

Interventions

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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.

Intervention Type DRUG

Topical gel (placebo formulation)

Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.

Intervention Type DRUG

Other Intervention Names

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TestimĀ®

Eligibility Criteria

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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
Minimum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Boston Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Shalender Bhasin

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shalender Bhasin, MD

Role: PRINCIPAL_INVESTIGATOR

Boston University Medical Center, Section of Endocrinology, Diabetes, and Nutrition

Shehzad Basaria, MD

Role: STUDY_DIRECTOR

Boston University Medical Center, Section of Endocrinology, Diabetes, and Nutrition

Wildon Farwell, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

VA Boston Healthcare System (Jamaica Plain Campus)

Locations

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Boston University Medical Center

Boston, Massachusetts, United States

Site Status

VA Boston Healthcare System (Jamaica Plain Campus)

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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. doi: 10.1093/ajcn/76.2.473.

Reference Type BACKGROUND
PMID: 12145025 (View on PubMed)

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. doi: 10.1093/gerona/56.5.b209.

Reference Type BACKGROUND
PMID: 11320101 (View on PubMed)

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. doi: 10.1210/jcem.86.2.7219.

Reference Type BACKGROUND
PMID: 11158037 (View on PubMed)

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. doi: 10.1016/0895-4356(91)90028-8.

Reference Type BACKGROUND
PMID: 1829756 (View on PubMed)

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.

Reference Type RESULT
PMID: 20592293 (View on PubMed)

Lee H, Hwang EC, Oh CK, Lee S, Yu HS, Lim JS, Kim HW, Walsh T, Kim MH, Jung JH, Dahm P. Testosterone replacement in men with sexual dysfunction. Cochrane Database Syst Rev. 2024 Jan 15;1(1):CD013071. doi: 10.1002/14651858.CD013071.pub2.

Reference Type DERIVED
PMID: 38224135 (View on PubMed)

Traustadottir 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.

Reference Type DERIVED
PMID: 29846604 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28981994 (View on PubMed)

Gagliano-Juca 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.

Reference Type DERIVED
PMID: 28950424 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23292288 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21697501 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18996225 (View on PubMed)

Other Identifiers

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U01AG014369

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AG0057

Identifier Type: -

Identifier Source: org_study_id

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