The Testosterone Trial in Older Men
The Testosterone Trials are a multi-center set of trials involving 12 clinical sites geographically distributed across the United States.
The primary specific aims are to test the hypotheses that testosterone treatment of elderly men whose serum testosterone concentrations are unequivocally low - and who have symptoms and objectively measured abnormalities in at least one of five areas that could be due to low testosterone (physical or sexual function, vitality, cognition, and anemia) - will result in more favorable changes in those abnormalities than placebo treatment.
Two additional trials have been incorporated into the T Trial. Only men enrolled in the T Trial are eligible to participate in these trials.
- The Cardiovascular Trial will examine if testosterone treatment results in more favorable changes in cardiovascular risk factors, compared to placebo.
- The Bone Trial will test the hypothesis that testosterone treatment will increase volumetric trabecular bone mineral density (vBMD) of the lumbar spine as measured by quantitative computed tomography (QCT), compared with placebo treatment.
A Pharmacokinetic (PK) Study is also being conducted within the context of the interventional T Trial. It will examine the variability of the serum testosterone (T) concentration after application of testosterone gel or placebo, four months after the start of treatment.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Randomized, Placebo-controlled, Double-blind Study of Five Coordinated Testosterone Treatment Trials in Older Men|
- Each of the 7 trials has its own primary outcome: [ Time Frame: 1 year ] [ Designated as safety issue: No ]
PHYSICAL FUNCTION: Increase from baseline of ≥ 50 m in 6 minute walk test. SEXUAL FUNCTION: Change from baseline in responses to Question 4 of the Harbor-UCLA Sexual Function Questionnaire.
VITALITY: Increase from baseline in score on the FACIT-Fatigue scale by ≥ 4 points.
COGNITIVE FUNCTION: Change from baseline in responses to the Wechsler Memory Scale Revised (WMS-R) Logical Memory II, in men with AAMI at baseline.
CARDIOVASCULAR: Change from baseline in non-calcified plaque volume as measured by CT angiography.
BONE: Percent change from baseline in volumetric bone mineral density of trabecular bone of the spine as measured by quantitative computed tomography (QCT) scan.
ANEMIA: Increase in hemoglobin by ≥ 1.0 g/dL in men with anemia of unknown cause at baseline.
- The 7 trials have secondary outcomes: [ Time Frame: 1 year ] [ Designated as safety issue: No ]
PHYSICAL FUNCTION: Improvement of ≥ 8 on PF-10/SF-36; change in 6-minute walk distance; both outcomes combined.
SEXUAL FUNCTION: Change Harbor UCLA 7-day Sexual Function Questionnaire, DISF-II-M, IIEF.
VITALITY: Change on the Vitality Scale/SF-36, PANAS, PHQ-9. COGNITIVE FUNCTION: Change on BVRT, Card Rotations, Trails A minus the log-transformed total time for Trails B, 3MSE.
CARDIOVASCULAR: Change measured by CT in log-transformed coronary artery calcium, total plaque volume and subcutaneous fat; change in HgA1C in men not being treated for diabetes; change in HOMA-IR (not limited to those enrolled in cardiovascular trial).
BONE: Change (QCT) in trabecular vBMD, bone strength, cortical bone strength and whole bone strength of the spine; trabecular bone vBMD and whole bone strength of the hip; areal bone mineral density of the spine (DEXA).
ANEMIA: Change from baseline in continuous hemoglobin.
- Exploratory Outcomes [ Time Frame: 1 year ] [ Designated as safety issue: No ]A number of exploratory outcomes have been pre-specified.
|Study Start Date:||November 2009|
|Estimated Study Completion Date:||June 2016|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Active Comparator: AndroGel® (testosterone gel)
AndroGel is applied to the shoulders, abdomen or upper arms once a day. Subjects will be instructed to wash their hands after application and not to have contact with women or children while the gel is wet. They will also be asked not to bathe or get this area wet for five hours after application. The initial dose of AndroGel will be 5.0 g (containing 50 mg of testosterone) once a day.
Drug: AndroGel® (testosterone gel)
Testosterone levels will be measured at regular intervals in order to achieve a testosterone level in the desired range.
Other Name: Testosterone gel
Placebo Comparator: Placebo gel
Placebo gel is identical to the testosterone gel and is supplied in an identical pump bottle container. It is applied to the shoulders, abdomen or upper arms once a day. Subjects will be instructed to follow the same precautions to avoid contact with others.
As men get older, they experience many conditions, often together, that eventually result in the inability to perform many activities of daily living, an increased propensity to fall, and decreased independence. These conditions include mobility disability and low vitality. Elderly men also experience increased anemia, metabolic syndrome, decreased sexual function and memory impairment. These conditions likely have multiple causes, but one cause that could contribute to all of them is a low serum testosterone concentration. When young hypogonadal men are treated with testosterone, they experience improvements in sexual function, muscle mass and strength, bone mineral density, sense of well being, and anemia. However, the benefits of testosterone therapy in older men with age-related decline in testosterone concentration are not known and are the subject of this investigation.
Participants will be treated with testosterone or placebo gel for 1 year. The dose will be adjusted in a blinded fashion to achieve a target T level range. Participants will be followed for one additional year following the treatment phase to assess adverse events.
- Men participating in the Cardiovascular Trial will be assessed for changes in atherosclerotic plaque burden from 0 to 12 months.
- Men participating in the Bone Trial will be assessed by QCT of the spine and hip, DXA of the spine and hip and clinical fractures at 0 and 12 months.
- Men participating in the PK Study will attend 3 additional study visits for blood draws at the time of the 4-month assessment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00799617
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|University of California San Diego|
|La Jolla, California, United States, 92093|
|Center for Men's Health LA BioMed at Harbor-UCLA Medical Center|
|Torrance, California, United States, 90501|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32611|
|United States, Illinois|
|Chicago, Illinois, United States, 60208|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02215|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, New York|
|Albert Einstein College of Medicine|
|Bronx, New York, United States, 10461|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15261|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 76798|
|United States, Washington|
|VA Puget Sound Health Care System|
|Seattle, Washington, United States, 98108|
|Principal Investigator:||Peter J Snyder, MD||University of Pennsylvania|