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TerminatedNCT00240981Updated Feb 23, 2017Results posted

TOM: Testosterone in Older Men With Sarcopenia

A Phase 4 interventional study of Topical testosterone gel 1% (active formulation) and Topical gel (placebo formulation) in Sarcopenia, Hypogonadism and Muscular Diseases, sponsored by Boston Medical Center. Terminated at 2 sites in United States. Open to male participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2017-02-23.

Sponsored by Boston Medical Center · Phase 4, Interventional, and Treatment

Why this study was terminated
Higher incidence of cardiovascular events in the testosterone arm of the trial. Decision taken by the DSMB on December 31st, 2009.
Phase
Phase 4
Study type
Interventional
Enrollment
209
Allocation
Randomized
Ages
65 Years and older
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Sarcopenia
  • Hypogonadism
  • Muscular Diseases

Keywords

  • Andropause
  • frailty
  • hormone replacement therapy
  • Aging
03

In context

Muscular Diseases

280 studies on the registry are indexed under Muscular Diseases; 63 are open to participants now.

This study's enrollment of 209 is above the median of 34 across 157 interventional studies indexed under Muscular Diseases.

Browse Muscular Diseases studies →

Lead sponsor

Boston Medical Center is the lead sponsor of 314 studies on the registry; 34 are open to participants now.

Of its 34 completed or terminated interventional studies of FDA-regulated products, 28 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

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

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
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Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
209 participants (actual)

Study arms

  • Experimental
    Treatment

    Drug: Topical testosterone gel 1% (active formulation)

  • Placebo comparator
    Placebo

    Drug: Topical gel (placebo formulation)

Interventions

  • DrugTopical 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.

    Also known as: Testim®

  • DrugTopical gel (placebo formulation)

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

06

What researchers measure

Primary outcomes

  1. Changes in Physical Performance Measured by an Exercise Testing Regimen

    Primary outcome was a change from baseline in leg-press strength at 6 months.

    Time frame: baseline and 6 months

Secondary outcomes

  1. Chest-Press

    Change from baseline in chest press strength at 6 months

    Time frame: baseline and 6 months

  2. Stair-climbing Test (Without a Load)

    Change from baseline in the stair-climbing test (without a load) at 6 months.

    Time frame: baseline and 6 month

  3. Grip Strength

    Change from baseline in grip strength in the dominant hand.

    Time frame: baseline and 6 months

  4. 50-Meter Walking Speed (Without a Load)

    Change from baseline 50-Meter Walking Speed (without a load) at 6 months

    Time frame: baseline and 6 months

  5. Stair-climbing Test (Loaded)

    Change from baseline in Stair-climbing Test (loaded)

    Time frame: baseline and 6 months

  6. Late Life Functional Disability Index (LLFDI)

    Percent change from baseline in the late life functional disability index at 6 months

    Time frame: baseline and 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)

    Change from baseline 50-Meter Walking Speed (with a load) at 6 months

    Time frame: baseline and 6 months

07

Results

Posted Feb 23, 2017

Participant flow

All participants provided written, informed consent. Recruitment took place at VAHCS, NERI, and BUMC. Outcome assessments were performed at BUMC. The study consisted of a 24- week intervention followed by a 12-week observation period. Enrollment took place between September 2005 and December 2009.

Participant flow — Overall Study
MilestoneTreatmentPlacebo
Started106103
Intent to treat sample8283
Completed6870
Not completed3833

Outcome measures

PrimaryChanges in Physical Performance Measured by an Exercise Testing Regimen

Primary outcome was a change from baseline in leg-press strength at 6 months.

Time frame:
baseline and 6 months
Reported as:
Mean · Newtons
Changes in Physical Performance Measured by an Exercise Testing Regimen
NewtonsTreatmentPlacebo
Changes in Physical Performance Measured by an Exercise Testing Regimen156.9 (89.2 to 224.6)27.1 (-28.3 to 82.6)
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.003 (The unadjusted analysis using two-sample Student's t-tests of equal change in the trial groups, allowing unequal variance.) · Mean difference (net): 129.8 · 95% CI 43.9 to 215.6
  • Treatment vs Placebo · Regression, Linear · p = 0.004 (Adjusted analysis used multiple linear regression, with adjustment for baseline total score on the Short Physical Performance Battery, and self-report of limitations in mobility.) · Mean difference (net): 129.4 · 95% CI 43.5 to 215.4
SecondaryChest-Press

Change from baseline in chest press strength at 6 months

Time frame:
baseline and 6 months
Reported as:
Mean · Newtons
Chest-Press
NewtonsTreatmentPlacebo
Chest-Press34.7 (18.7 to 51.4)0.28 (-13.8 to 14.3)
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.002 (Unadjusted) · Mean difference (net): 34.5 · 95% CI 13.2 to 55.8
  • Treatment vs Placebo · Regression, Linear · p = 0.002 (Adjusted) · Mean difference (net): 34.5 · 95% CI 13.1 to 56.2
SecondaryStair-climbing Test (Without a Load)

Change from baseline in the stair-climbing test (without a load) at 6 months.

Time frame:
baseline and 6 month
Reported as:
Mean · Watts
Stair-climbing Test (Without a Load)
WattsTreatmentPlacebo
Stair-climbing Test (Without a Load)19.5 (7.4 to 31.5)10.7 (-2.9 to 24.3)
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.34 (Unadjusted) · Mean difference (net): 8.7 · 95% CI -9.2 to 26.7
  • Treatment vs Placebo · Regression, Linear · p = 0.37 (Adjusted.) · Mean difference (net): 8.1 · 95% CI -9.9 to 26.2
SecondaryGrip Strength

Change from baseline in grip strength in the dominant hand.

Time frame:
baseline and 6 months
Reported as:
Mean · Kilograms
Grip Strength
KilogramsTreatmentPlacebo
Grip Strength1.0 (-0.1 to 2.0)0.7 (-0.3 to 1.7)
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.69 (Unadjusted) · Mean difference (net): .27 · 95% CI -1.1 to 1.7
  • Treatment vs Placebo · Regression, Linear · p = 0.71 (Adjusted.) · Mean difference (net): 0.26 · 95% CI -1.1 to 1.7
Secondary50-Meter Walking Speed (Without a Load)

Change from baseline 50-Meter Walking Speed (without a load) at 6 months

Time frame:
baseline and 6 months
Reported as:
Mean · meters/second
50-Meter Walking Speed (Without a Load)
meters/secondTestosteronePlacebo
50-Meter Walking Speed (Without a Load)0.074 (-0.004 to 0.153)0.024 (-0.018 to 0.066)
Statistical analysis
  • Testosterone vs Placebo · t-test, 2 sided · p = 0.26 (Unadjusted.) · Mean difference (net): 0.050 · 95% CI -0.035 to 0.135
  • Testosterone vs Placebo · Regression, Linear · p = 0.27 (Adjusted) · Mean difference (net): 0.048 · 95% CI -0.037 to 0.133
SecondaryStair-climbing Test (Loaded)

Change from baseline in Stair-climbing Test (loaded)

Time frame:
baseline and 6 months
Reported as:
Mean · Watts
Stair-climbing Test (Loaded)
WattsTreatmentPlacebo
Stair-climbing Test (Loaded)39.2 (14.4 to 64.0)9.0 (-8.4 to 26.4)
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.05 (Unadjusted.) · Mean difference (net): 30.2 · 95% CI 0.3 to 60.1
  • Treatment vs Placebo · Regression, Linear · p = 0.05 (Adjusted) · Mean difference (net): 29.7 · 95% CI 0.2 to 59.3
SecondaryLate Life Functional Disability Index (LLFDI)

Percent change from baseline in the late life functional disability index at 6 months

Time frame:
baseline and 6 months
Reported as:
Mean · units on a scale
Late Life Functional Disability Index (LLFDI)
units on a scaleTreatmentPlacebo
Late Life Functional Disability Index (LLFDI)61.2 (38 to 100)61.7 (38 to 100)
SecondaryTotal Lean Mass
Time frame:
baseline, 3 months, and 6 months
Reported as:
Mean · Kilograms
Total Lean Mass
KilogramsTreatmentPlacebo
Baseline55.1 ± 6.956.5 ± 6.5
3 Months (N=73,75)57.2 ± 7.156.7 ± 6.2
6 Months (N=77,80)56.1 ± 6.956.2 ± 6.3
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.2 (Month 3 Measures) · Mean difference (net): 1.8 · 95% CI 1.2 to 2.5
  • Treatment vs Placebo · t-test, 2 sided · p = <.0001 (Month 6 Measures) · Mean difference (net): 1.5 · 95% CI 0.4 to 2.2
SecondaryTotal Fat Mass
Time frame:
baseline, 3 months, and 6 months
Reported as:
Mean · Kilograms
Total Fat Mass
KilogramsTreatmentPlacebo
Baseline (N=82,81)26.2 ± 7.528 ± 8.4
3 Months (N=73,75)24.9 ± 7.128 ± 8.1
6 Months (N=77,80)24.0 ± 6.827.5 ± 7.9
Statistical analysis
  • Treatment vs Placebo · t-test, 2 sided · p = 0.002 (3 Months Measures) · Mean difference (net): -1.7 · 95% CI -2.7 to -0.6
  • Treatment vs Placebo · t-test, 2 sided · p = <.0001 (6 Month Measures) · Mean difference (net): -2.0 · 95% CI -2.8 to -1.2
Secondary50-Meter Walking Speed (With a Load)

Change from baseline 50-Meter Walking Speed (with a load) at 6 months

Time frame:
baseline and 6 months
Reported as:
Mean · meters/second
50-Meter Walking Speed (With a Load)
meters/secondTestosteronePlacebo
50-Meter Walking Speed (With a Load)0.139 (0.023 to 0.256)0.065 (0.013 to 0.116)
Statistical analysis
  • Testosterone vs Placebo · t-test, 2 sided · p = 0.24 (Unadjusted.) · Mean difference (net): 0.074 · 95% CI -0.05 to 0.19
  • Testosterone vs Placebo · Regression, Linear · p = 0.14 (Adjusted.) · Mean difference (net): 0.090 · 95% CI -0.030 to 0.209

Adverse events

Collected over Adverse event data were collected throughout the entire study period (4 years and 3 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment—16/106 (15.1%)35/106 (33%)
Placebo—8/103 (7.8%)10/103 (9.7%)
Most frequent serious events
Showing 10 of 27
Most frequent serious events
EventTreatmentPlacebo
Community acquired pneumoniaInfections and infestations1/1061/103
Syncope resulting in hospitalizationNervous system disorders0/1061/103
Painful neuropathyNervous system disorders0/1061/103
Hepatocellular carcinomaHepatobiliary disorders0/1061/103
Intestinal obstructionGastrointestinal disorders0/1061/103
Transurethral resection of prostateSurgical and medical procedures0/1061/103
Abdominal painGastrointestinal disorders0/1061/103
Splenic ruptureInjury, poisoning and procedural complications0/1061/103
Inflammatory colonic mass related to Crohn's DiseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1061/103
Rectal bleeding from Crohn's DiseaseGastrointestinal disorders0/1061/103
Most frequent other events
Most frequent other events
EventTreatmentPlacebo
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders11/1066/103
Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders9/1060/103
General disorders and administration site conditionsGeneral disorders5/1060/103
Infections and infestationsInfections and infestations5/1064/103
Reproductive system and breast disordersReproductive system and breast disorders5/1060/103

Baseline characteristics

Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter or a free serum testosterone level of less than 50 pg per milliliter were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months.

Age, Categorical
Age, Categorical(Participants)TreatmentPlaceboTotal
<=18 years000
Between 18 and 65 years000
>=65 years106103209
Age, Continuous
Age, Continuous(Years)TreatmentPlaceboTotal
Mean74 ± 674 ± 574 ± 5.4
Sex: Female, Male
Sex: Female, Male(Participants)TreatmentPlaceboTotal
Female000
Male106103209
Region of Enrollment
Region of Enrollment(participants)TreatmentPlaceboTotal
United States106103209
08

Study locations

2 sites
  • Boston University Medical Center
    Boston, Massachusetts 02118, United States
  • VA Boston Healthcare System (Jamaica Plain Campus)
    Boston, Massachusetts 02130, United States
09

References and documents

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. doi: 10.1093/ajcn/76.2.473. PubMed 12145025 ↗
  • 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. PubMed 11320101 ↗
  • 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. PubMed 11158037 ↗
  • 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. PubMed 1829756 ↗
  • 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. PubMed 20592293 ↗
  • 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. PubMed 29846604 ↗
  • 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. PubMed 28981994 ↗
  • 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. PubMed 28950424 ↗
  • 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. PubMed 23292288 ↗
  • 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. PubMed 21697501 ↗
  • 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. PubMed 18996225 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 23, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00240981
Lead sponsor
Boston Medical Center
Collaborators
National Institute on Aging (NIA)
Responsible party
Shalender Bhasin (Professor of Medicine, Boston Medical Center) — Principal investigator
First posted
Oct 18, 2005
Start date
Jan 2005
Primary completion
Dec 2009
Completion
Dec 2009
Results posted
Feb 23, 2017
Last update
Feb 23, 2017

Study contacts

Shalender Bhasin, MD
principal investigator · Boston University Medical Center, Section of Endocrinology, Diabetes, and Nutrition
Shehzad Basaria, MD
study director · Boston University Medical Center, Section of Endocrinology, Diabetes, and Nutrition
Wildon Farwell, MD, MPH
principal investigator · VA Boston Healthcare System (Jamaica Plain Campus)

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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