The National Institutes of Health (NIH) has launched a clinical trial to determine if testosterone treatment of men 65 years and older will help their walking, vitality, sexual function, memory, and blood count. This trial, called The Testosterone Trial, or TTrial, will be conducted in 800 men in 12 cities across the United States.
As men age, their serum testosterone concentrations fall, so that in their 70s, 30% per cent of men have levels that would be considered low for young men. Also as men age, their physical function, sexual function, vitality, and cognitive function decrease, and they are more likely to become anemic. In addition, cardiovascular disease and diabetes increase. One reason to think that the decrease in testosterone might be a cause of these functional impairments in elderly men is that young men who develop low testosterone concentrations because of pituitary or testicular disease also experience these functional impairments. Prior trials to determine if testosterone treatment would improve these functional impairments in elderly men gave results that were tantalizing but not conclusive, possibly because the numbers of men who participated were too small and the testosterone levels before treatment were not unequivocally low.
Goal of the Study
The overall goal of The Testosterone Trial is to test the hypothesis that testosterone treatment, compared to placebo treatment, of men who are 65 years or older and have unequivocally low serum testosterone concentrations will improve their physical function, sexual function, vitality, cognitive function, and low hemoglobin concentration, as well as decrease risk factors for cardiovascular and diabetes.
The Testosterone Trial is a coordinated set of six trials: Physical Function Trial, Sexual Function Trial, Vitality Trial, Cognitive Function Trial, Anemia Trial and Cardiovascular Trial. A man can participate in more than one trial if he qualifies and agrees to participate.
To qualify for The Testosterone Trial, a man must be 65 years or older and have a serum testosterone concentration less than 250 ng/dL at 8AM on two occasions. He must also have symptoms and measured functional impairments in walking, sexual interest, or vitality. Men must also be at relatively low risk for prostate cancer and not have severe lower urinary tract symptoms.
Treatment. Men who qualify and agree to participate will be assigned randomly to receive either a testosterone gel or a placebo gel for one year. The dose of testosterone gel will be adjusted to keep the serum testosterone concentration within the normal range for young men.
Assessment of Efficacy
Physical function will be assessed by the distance walked in six minutes, as well as the PF10 questionnaire and ascertainment of falls. Sexual function will be assessed by the Harbor-UCLA 7-day Sexual Diary, as well as by the International Index of Erectile Function and the Derogatis Interview for Sexual Functioning for Men. Vitality will be assessed by the FACIT-Fatigue Scale, Vitality Scale of the SF-36, Positive and Negative Affect Scales, and PHQ-9 depression scale. Cognitive function will be assessed by the Wechsler Memory Scale Revised Logical Memory II subscale recall, Benton Visual Retention Test, Card Rotation test, and Trail Making Test. Anemia will be assessed by hemoglobin concentration. Cardiovascular and metabolic risk will be assessed by blood tests for lipids and markers of inflammation, clotting and vascular function.
Monitoring for Potential Adverse Effects
The possible development of prostate diseases will be assessed by digital rectal examination, PSA levels, and the International Prostate Symptoms Score. General medical events will be recorded during the year of treatment and for a year after discontinuation of treatment.
The Steering Committee provides scientific oversight to The Testosterone Trial. The Steering Committee consists of Peter J. Snyder, Principal Investigator and Chair, Elizabeth Barrett-Connor, Shalender Bhasin, Jane Cauley, David Cella, Jill Crandall, Glenn Cunningham, Susan Ellenberg, Kristine Ensrud, John Farrar, Thomas Gill, Cora Lewis, Alvin Matsumoto, Mark E. Molitch, Marco Pahor, Susan Resnick, Raymond Rosen, and Ronald S. Swerdloff.
Data Coordinating Center
The Clinical Research Computing Unit, in the Department of Biostatistics and Clinical Epidemiology at the University of Pennsylvania, is the Data Coordinating Center (DCC). It coordinates all activities of the Trial.
Clinical Trial Sites
The 12 clinical trial sites are:
Albert Einstein College of Medicine, Bronx, NY
Baylor College of Medicine, Houston, TX
Boston Medical Center, Boston, MA
Northwestern University Feinberg School of Medicine, Chicago, Il
University of Alabama at Birmingham, Birmingham, AL
University of California at Los Angeles, Harbor-UCLA Medical Center, Torrance, CA
University of California at San Diego, La Jolla, CA
University of Florida, Gainesville, FL
University of Pittsburgh, Pittsburgh, PA
University of Minnesota, Minneapolis, MN
Unviersity of Washington, VA Puget Sound Health Care System, Seattle, WA
Yale School of medicine, New Haven CT
Cedars-Sinai Medical Center – Genetics center
Criterium – Interactive voice response system
Fred Hutchinson Cancer Research Center – Prostate tissue reading center
Investigational Drug Service, University of Pennsylvania – Central pharmacy
KAI – Monitoring of trial sites
Quest Laboratories – Central laboratory
Wake Forest University – Cognitive function reading center
This trial is supported by the National Institute on Aging (NIA), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Child Health and Human Development (NICHD), the National Heart, Lung and Blood Institute (NHLBI), and Solvay Pharmaceuticals, Inc.