Healthy
Conditions
Keywords
andropause, hypogonadism, AndroGel, exercise, PRT, Testosterone, T supplementation
Brief summary
The purpose of this study is to evaluate the effects of testosterone supplementation (AndroGel) on body composition, strength, endurance, cognition, and function in older men.
Detailed description
Studies suggest that testosterone (T) replacement in healthy elderly men has beneficial effects on body composition, muscle, bone, memory, and behavior, but the risks of chronic treatment, especially on the prostate, heart, and sleep quality, are not entirely clear. Therefore, it is most desirable to supplement into the lowest effective range in elderly men. However, the effects of lower than usual replacement T doses have not been well studied. Furthermore, the possible important interaction of exercise to enhance the positive effects of T supplementation, yet mitigate the possible side effects, has not been studied in older men. This one-year study will enroll 150 men with low-normal to slightly below normal serum total T levels. Participants will be randomized into one of 6 treatment groups to receive T supplementation (AndroGel) of 25mg/day, 50 mg/day or a placebo crossed with progressive resistance training (PRT) exercise 3 times a week versus none. At the end of the study, participants in the exercise-control group will be offered PRT. Please see link below for updated version of full protocol.
Interventions
DRUGLowT
Low Dose Testosterone Group applies one 2.5 gm active packet and one placebo packet, titrated to a target blood range of 400-550 pg/ml)during the first 12 weeks. Total exposure duration is 52 weeks.
BEHAVIORALResistance Training
Weight training 45-60 minutes 3 times per week
DRUGPlacebo
2.5 gm gel packets applied once daily. Sham adjustments made during the first 12 weeks. Duration is 52 weeks.
DRUGHighT
High Dose Testosterone Group applies two 2.5 gm active packets, titrated to a target blood range of 600-1000 pg/ml)during the first 12 weeks. Total exposure duration is 52 weeks.
Sponsors
National Institute on Aging (NIA)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy, untrained men 60 years or older with low-normal testosterone levels (200-350ng/dL) * Must reside in the Denver metro area
Exclusion criteria
* Prostate/breast cancer * Unable to exercise safely * severe obesity (\>34 body mass index \[BMI\]) * Polycythemia * Diabetes * Use of drugs that could affect T levels * Cognitive dysfunction (MMSE less than 24) * PSA above the age-adjusted normal level or AUA greater than 19 * Unable to pass stress test due to active CAD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physical Function (CS-PFP Total Score) | Baseline and 12 months | Continuous-scale physical function performance test (CS-PFP) which comprises 15 everyday tasks requiring upper and lower body strength and flexibility, balance, coordination and endurance. The CS-PFP was developed to measure performance in higher functioning adults with minimal floor or ceiling effects, and is valid, reliable and sensitive to change. Total and domain scores are scaled from 0 to 100, with higher scores indicating better function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Upper Body Muscle Strength (1-RM, kg) | Baseline and 12 months | The maximal weight a participant could lift once (1-repetition maximum, 1-RM) was assessed at baseline and 12 months. The average of the difference from baseline in 4 upper-body 1-RM measures (bench press,incline press, overhead pull-down, and seated row) are represented. |
| Lower Body Muscle Strength (1-RM, kg) | Baseline and 12 months | The maximal weight a participant could lift once \[1-repetition maximum, 1-RM\] was assessed at baseline and 12 months. The average of the difference from baseline in 3 lower-body 1-RM measures (knee extension, knee flexion, and seated leg press)) are represented. |
| Power (Power Rig, Watts) | Baseline and 12 months | Leg extensor power was evaluated using a Nottingham leg extensor power rig (watts). |
| Fat Mass (kg) | Baseline and 12 months | Total change in Fat mass (kg) as evaluated by DXA |
| Fat Free Mass (kg) | Baseline and 12 months | Total change in Fat free mass (kg) as evaluated by DXA |
Countries
United States
Participant flow
Recruitment details
Recruitment from January 2005 through August 2009 of community dwelling men \>=60 years of age in the Denver metropolitan area with active attempts to recruit men from all ethnic populations.
Pre-assignment details
see eligibility criteria
Participants by arm
| Arm | Count |
|---|---|
| LowT+Resistance Training Low Dose Testosterone Group applies one 2.5 gm active packet and one placebo packet, titrated to a target blood range of 400-550 pg/ml)
1 year standard Progressive Resistance Training(PRT) program | 28 |
| LowT+No Resistance Training Low Dose Testosterone Group applies one 2.5 gm active packet and one placebo packet, titrated to a target blood range of 400-550 pg/ml)
No exercise program | 28 |
| HighT+Resistance Training High Dose Testosterone Group applies two 2.5 gm active packets, titrated to a target blood range of 600-1000 pg/ml)
1 year standard Progressive Resistance Training(PRT) program | 28 |
| HighT+No Resistance Training High Dose Testosterone Group applies two 2.5 gm active packets, titrated to a target blood range of 600-1000 pg/ml)
No exercise program | 27 |
| Placebo+Resistance Training Placebo Group applies two 2.5 gm placebo packets
1 year standard Progressive Resistance Training(PRT) program | 28 |
| Placebo+No Resistance Training Placebo group applies two 2.5 gm placebo packets
No exercise program | 28 |
| Total | 167 |
Baseline characteristics
| Characteristic | LowT+No Resistance Training | HighT+Resistance Training | HighT+No Resistance Training | LowT+Resistance Training | Placebo+Resistance Training | Placebo+No Resistance Training | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 11 Participants | 14 Participants | 16 Participants | 12 Participants | 16 Participants | 85 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 17 Participants | 13 Participants | 12 Participants | 16 Participants | 12 Participants | 82 Participants |
| Age, Continuous | 65.6 years STANDARD_DEVIATION 4.5 | 64.3 years STANDARD_DEVIATION 4.6 | 65.3 years STANDARD_DEVIATION 5.5 | 67.3 years STANDARD_DEVIATION 7.6 | 64.7 years STANDARD_DEVIATION 4.5 | 66.6 years STANDARD_DEVIATION 5.4 | 65.7 years STANDARD_DEVIATION 5.5 |
| Region of Enrollment United States | 28 participants | 28 participants | 27 participants | 28 participants | 28 participants | 28 participants | 167 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 28 Participants | 28 Participants | 27 Participants | 28 Participants | 28 Participants | 28 Participants | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 47 | 14 / 47 | 25 / 49 |
| serious Total, serious adverse events | 30 / 47 | 33 / 47 | 38 / 49 |
Outcome results
Primary
Physical Function (CS-PFP Total Score)
Continuous-scale physical function performance test (CS-PFP) which comprises 15 everyday tasks requiring upper and lower body strength and flexibility, balance, coordination and endurance. The CS-PFP was developed to measure performance in higher functioning adults with minimal floor or ceiling effects, and is valid, reliable and sensitive to change. Total and domain scores are scaled from 0 to 100, with higher scores indicating better function.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + No PRT | Physical Function (CS-PFP Total Score) | 3.1 units on a scale | Standard Deviation 6.7 |
| Placebo + PRT | Physical Function (CS-PFP Total Score) | 3.6 units on a scale | Standard Deviation 8 |
| Any T + No PRT | Physical Function (CS-PFP Total Score) | 0.8 units on a scale | Standard Deviation 7.3 |
| Any T + PRT | Physical Function (CS-PFP Total Score) | 3.3 units on a scale | Standard Deviation 7.4 |
Comparison: As prespecified, the lower- and higher-range T groups were combined (any T). The primary analysis was conducted in the PRT groups and compared CS-PFP at 12 months with any T to placebo, adjusted for baseline CS-PFP score.p-value: <0.025Regression, Linear
Comparison: As prespecified, the lower- and higher-range T groups were combined (any T). To address whether the effects of any T on physical function are the same without PRT, the analysis was also conducted in the No PRT groups, comparing CS-PFP at 12 months with any T to placebo, adjusted for baseline CS-PFP score.p-value: <0.025Regression, Linear
Secondary
Fat Free Mass (kg)
Total change in Fat free mass (kg) as evaluated by DXA
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + No PRT | Fat Free Mass (kg) | 0.1 kg | Standard Deviation 1.7 |
| Placebo + PRT | Fat Free Mass (kg) | 0.4 kg | Standard Deviation 2.1 |
| Any T + No PRT | Fat Free Mass (kg) | 1.0 kg | Standard Deviation 2.2 |
| Any T + PRT | Fat Free Mass (kg) | 2.1 kg | Standard Deviation 2.4 |
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in fat free mass measured by dual x-ray absorptiometry (DXA) with any T to placebo in subjects assigned to PRT.p-value: <0.05Regression, Linear
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in fat free mass measured by dual x-ray absorptiometry (DXA) with any T to placebo in subjects assigned to no PRT.p-value: <0.05Regression, Linear
Secondary
Fat Mass (kg)
Total change in Fat mass (kg) as evaluated by DXA
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + No PRT | Fat Mass (kg) | 0.7 kg | Standard Deviation 2.3 |
| Placebo + PRT | Fat Mass (kg) | -0.6 kg | Standard Deviation 1.7 |
| Any T + No PRT | Fat Mass (kg) | -1.0 kg | Standard Deviation 2.3 |
| Any T + PRT | Fat Mass (kg) | -1.8 kg | Standard Deviation 2.5 |
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in fat mass measured by dual x-ray absorptiometry (DXA) with any T to placebo in subjects assigned to PRT.p-value: <0.05Regression, Linear
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in fat mass measured by dual x-ray absorptiometry (DXA) with any T to placebo in subjects assigned to no PRT.p-value: <0.05Regression, Linear
Secondary
Lower Body Muscle Strength (1-RM, kg)
The maximal weight a participant could lift once \[1-repetition maximum, 1-RM\] was assessed at baseline and 12 months. The average of the difference from baseline in 3 lower-body 1-RM measures (knee extension, knee flexion, and seated leg press)) are represented.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + No PRT | Lower Body Muscle Strength (1-RM, kg) | 9.4 kg | Standard Deviation 11.6 |
| Placebo + PRT | Lower Body Muscle Strength (1-RM, kg) | 27.0 kg | Standard Deviation 17 |
| Any T + No PRT | Lower Body Muscle Strength (1-RM, kg) | 10.5 kg | Standard Deviation 10.9 |
| Any T + PRT | Lower Body Muscle Strength (1-RM, kg) | 28.0 kg | Standard Deviation 19.7 |
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in average lower body strength with any T to placebo in subjects assigned to PRT.p-value: <0.05Regression, Linear
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in average lower body strength with any T to placebo in subjects assigned to no PRT.p-value: <0.05Regression, Linear
Secondary
Power (Power Rig, Watts)
Leg extensor power was evaluated using a Nottingham leg extensor power rig (watts).
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + No PRT | Power (Power Rig, Watts) | 4.5 Watts | Standard Deviation 34.6 |
| Placebo + PRT | Power (Power Rig, Watts) | 24.3 Watts | Standard Deviation 62 |
| Any T + No PRT | Power (Power Rig, Watts) | 0.8 Watts | Standard Deviation 36.9 |
| Any T + PRT | Power (Power Rig, Watts) | 5.1 Watts | Standard Deviation 51.1 |
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in leg extensor power with any T to placebo in subjects assigned to PRT.p-value: <0.05Regression, Linear
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in leg extensor power with any T to placebo in subjects assigned to no PRT.p-value: <0.05Regression, Linear
Secondary
Upper Body Muscle Strength (1-RM, kg)
The maximal weight a participant could lift once (1-repetition maximum, 1-RM) was assessed at baseline and 12 months. The average of the difference from baseline in 4 upper-body 1-RM measures (bench press,incline press, overhead pull-down, and seated row) are represented.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + No PRT | Upper Body Muscle Strength (1-RM, kg) | 4.3 kg | Standard Deviation 7.7 |
| Placebo + PRT | Upper Body Muscle Strength (1-RM, kg) | 25.5 kg | Standard Deviation 11.3 |
| Any T + No PRT | Upper Body Muscle Strength (1-RM, kg) | 7.8 kg | Standard Deviation 6.9 |
| Any T + PRT | Upper Body Muscle Strength (1-RM, kg) | 24.3 kg | Standard Deviation 11.6 |
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in average upper body strength with any T to placebo in subjects assigned to PRT.p-value: <0.05Regression, Linear
Comparison: As prespecified, the lower- and higher-range T groups were combined (Any T). The analysis compared change from baseline to 12 months in average upper body strength with any T to placebo in subjects assigned to no PRT.p-value: <0.05Regression, Linear