TOM: Testosterone in Older Men With Sarcopenia

• Sponsor: Boston Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00240981
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 209
• Locations: 2
• Arms: 2
• Duration (Months): 59
• Patients Per Site: 104.5
• Patients Per Site Per Month: 1.8

Study Details

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
• 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: Jan 1, 2005
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 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 Names: 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 [baseline and 6 months]

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

Secondary Outcome Measures

1. Chest-Press [baseline and 6 months]

   Change from baseline in chest press strength at 6 months

2. Stair-climbing Test (Without a Load) [baseline and 6 month]

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

3. Grip Strength [baseline and 6 months]

   Change from baseline in grip strength in the dominant hand.

4. 50-Meter Walking Speed (Without a Load) [baseline and 6 months]

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

5. Stair-climbing Test (Loaded) [baseline and 6 months]

   Change from baseline in Stair-climbing Test (loaded)

6. Late Life Functional Disability Index (LLFDI) [baseline and 6 months]

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

7. Total Lean Mass [baseline, 3 months, and 6 months]

8. Total Fat Mass [baseline, 3 months, and 6 months]

9. 50-Meter Walking Speed (With a Load) [baseline and 6 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: 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:

• 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

	Site	City	State	Country	Postal Code
1	Boston University Medical Center	Boston	Massachusetts	United States	02118
2	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)

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: Shalender Bhasin, Professor of Medicine, Boston Medical Center
• ClinicalTrials.gov Identifier: NCT00240981
• Other Study ID Numbers: AG0057; U01AG014369
• First Posted: Oct 18, 2005
• Last Update Posted: Feb 23, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Shalender Bhasin, Professor of Medicine, Boston Medical Center: Andropause; frailty; hormone replacement therapy; Aging
• Additional relevant MeSH terms: Muscular Diseases; Sarcopenia; Hypogonadism; Testosterone

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	The participants were community-dwelling men, aged 65 years and older, with total testosterone between 100 and 350 ng/dL or free testosterone less than 50 pg/mL, and mobility limitation.

Arm/Group Title	Treatment	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	106	103
Intent to Treat Sample	82	83
COMPLETED	68	70
NOT COMPLETED	38	33

Baseline Characteristics

Arm/Group Title	Treatment	Placebo	Total
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.	Total of all reporting groups
Overall Participants	106	103	209
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	106 100%	103 100%	209 100%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	74 (6)	74 (5)	74 (5.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	106 100%	103 100%	209 100%
Region of Enrollment (participants) [Number]
United States	106 100%	103 100%	209 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants with baseline and at least one post baseline measure.

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	49	54
Mean (95% Confidence Interval) [Newtons]	156.9	27.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	The unadjusted analysis using two-sample Student's t-tests of equal change in the trial groups, allowing unequal variance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	129.8
	Confidence Interval	(2-Sided) 95%; 43.9 to 215.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	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.
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	129.4
	Confidence Interval	(2-Sided) 95%; 43.5 to 215.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Chest-Press
Description	Change from baseline in chest press strength at 6 months
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

Participants with baseline and 1 post baseline measure.

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	38	44
Mean (95% Confidence Interval) [Newtons]	34.7	0.28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Unadjusted
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	34.5
	Confidence Interval	(2-Sided) 95%; 13.2 to 55.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Adjusted
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	34.5
	Confidence Interval	(2-Sided) 95%; 13.1 to 56.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Stair-climbing Test (Without a Load)
Description	Change from baseline in the stair-climbing test (without a load) at 6 months.
Time Frame	baseline and 6 month

Outcome Measure Data

Analysis Population Description

Participants with baseline and one post baseline measure.

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	49	52
Mean (95% Confidence Interval) [Watts]	19.5	10.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments	Unadjusted
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.7
	Confidence Interval	(2-Sided) 95%; -9.2 to 26.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	Adjusted.
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.1
	Confidence Interval	(2-Sided) 95%; -9.9 to 26.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Grip Strength
Description	Change from baseline in grip strength in the dominant hand.
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

The participants with baseline and one post baseline measure are included.

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	63	70
Mean (95% Confidence Interval) [Kilograms]	1.0	0.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments	Unadjusted
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	.27
	Confidence Interval	(2-Sided) 95%; -1.1 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	Adjusted.
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; -1.1 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	50-Meter Walking Speed (Without a Load)
Description	Change from baseline 50-Meter Walking Speed (without a load) at 6 months
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

Participants with a baseline and one post baseline measure.

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	39	43
Mean (95% Confidence Interval) [meters/second]	0.074	0.024

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Unadjusted.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.050
	Confidence Interval	(2-Sided) 95%; -0.035 to 0.135
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments	Adjusted
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.048
	Confidence Interval	(2-Sided) 95%; -0.037 to 0.133
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Stair-climbing Test (Loaded)
Description	Change from baseline in Stair-climbing Test (loaded)
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

Participants with one baseline and one post baseline measure.

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	46	50
Mean (95% Confidence Interval) [Watts]	39.2	9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Unadjusted.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	30.2
	Confidence Interval	(2-Sided) 95%; 0.3 to 60.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Adjusted
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	29.7
	Confidence Interval	(2-Sided) 95%; 0.2 to 59.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Late Life Functional Disability Index (LLFDI)
Description	Percent change from baseline in the late life functional disability index at 6 months
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	56	55
Mean (95% Confidence Interval) [units on a scale]	61.2	61.7

8. Secondary Outcome

Title	Total Lean Mass
Time Frame	baseline, 3 months, and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	82	81
Baseline	55.1 (6.9)	56.5 (6.5)
3 Months (N=73,75)	57.2 (7.1)	56.7 (6.2)
6 Months (N=77,80)	56.1 (6.9)	56.2 (6.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2
	Comments	Month 3 Measures
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; 1.2 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	Month 6 Measures
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 0.4 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Total Fat Mass
Time Frame	baseline, 3 months, and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	82	81
Baseline (N=82,81)	26.2 (7.5)	28 (8.4)
3 Months (N=73,75)	24.9 (7.1)	28 (8.1)
6 Months (N=77,80)	24.0 (6.8)	27.5 (7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	3 Months Measures
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	6 Month Measures
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -2.8 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	50-Meter Walking Speed (With a Load)
Description	Change from baseline 50-Meter Walking Speed (with a load) at 6 months
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

Participants with a baseline and one post baseline measure.

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	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.	Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Measure Participants	26	29
Mean (95% Confidence Interval) [meters/second]	0.139	0.065

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	Unadjusted.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.074
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Adjusted.
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.090
	Confidence Interval	(2-Sided) 95%; -0.030 to 0.209
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected throughout the entire study period (4 years and 3 months)
Arm/Group Title	Treatment		Placebo
Arm/Group Description	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.		Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
All Cause Mortality
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/106 (15.1%)		8/103 (7.8%)
Cardiac disorders
Acute coronary syndrome	1/106 (0.9%)	1	0/103 (0%)	0
Myocardial infarction treated with angioplasty, pacemaker placement	1/106 (0.9%)	1	0/103 (0%)	0
Myocardial infarction	1/106 (0.9%)	1	0/103 (0%)	0
Panic attack	1/106 (0.9%)	1	0/103 (0%)	0
Congestive heart failure	1/106 (0.9%)	1	0/103 (0%)	0
Death, suspected myocardial infarction	1/106 (0.9%)	1	0/103 (0%)	0
Congestive heart failure exacerbation	1/106 (0.9%)	1	0/103 (0%)	0
Gastrointestinal disorders
Intestinal obstruction	0/106 (0%)	0	1/103 (1%)	1
Abdominal pain	0/106 (0%)	0	1/103 (1%)	1
Rectal bleeding from Crohn's Disease	0/106 (0%)	0	1/103 (1%)	1
Hepatobiliary disorders
Hepatocellular carcinoma	0/106 (0%)	0	1/103 (1%)	1
Infections and infestations
Cholecystitis	1/106 (0.9%)	1	0/103 (0%)	0
Appendicitis	1/106 (0.9%)	1	0/103 (0%)	0
Community acquired pneumonia	1/106 (0.9%)	1	1/103 (1%)	1
Injury, poisoning and procedural complications
Fracture of the tibia	1/106 (0.9%)	1	0/103 (0%)	0
Clozapine toxicity	1/106 (0.9%)	1	0/103 (0%)	0
Splenic rupture	0/106 (0%)	0	1/103 (1%)	1
Investigations
Prostate cancer	1/106 (0.9%)	1	0/103 (0%)	0
Metabolism and nutrition disorders
Diabetic foot ulcer	1/106 (0.9%)	1	0/103 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Inflammatory colonic mass related to Crohn's Disease	0/106 (0%)	0	1/103 (1%)	1
Nervous system disorders
Stroke	1/106 (0.9%)	1	0/103 (0%)	0
Bupropion toxicity	1/106 (0.9%)	1	0/103 (0%)	0
Syncope resulting in hospitalization	0/106 (0%)	0	1/103 (1%)	1
Painful neuropathy	0/106 (0%)	0	1/103 (1%)	1
Surgical and medical procedures
Angioplasty and coronary artery bypass grafting	1/106 (0.9%)	1	0/103 (0%)	0
Peripheral angioplasty and stenting	1/106 (0.9%)	1	0/103 (0%)	0
Transurethral resection of prostate	0/106 (0%)	0	1/103 (1%)	1
Other (Not Including Serious) Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/106 (33%)		10/103 (9.7%)
General disorders
General disorders and administration site conditions	5/106 (4.7%)	5	0/103 (0%)	0
Infections and infestations
Infections and infestations	5/106 (4.7%)	5	4/103 (3.9%)	4
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	11/106 (10.4%)	11	6/103 (5.8%)	6
Reproductive system and breast disorders
Reproductive system and breast disorders	5/106 (4.7%)	5	0/103 (0%)	0
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	9/106 (8.5%)	9	0/103 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.