Testosterone Replacement in Older Men and Atherosclerosis Progression (TEAAM)
As men grow older, their testosterone levels decrease with age. One-third of men, 70 years of age or older, have low testosterone levels. It is known that short-term testosterone replacement is safe, and can increase muscle strength and physical function, but the risks of long-term testosterone replacement in older men with low testosterone levels are incompletely understood.
Atherosclerosis is characterized by thickening of the artery walls, and the narrowing of the blood vessels as cholesterol is deposited in the lining of the arteries. It is the major cause of cardiovascular disease including ischemic heart disease (heart attacks) and stroke. Although, historically, there has been a widespread perception that higher levels of testosterone might increase the risk of atherosclerosis, the evidence from research does not support this. In observational studies, higher testosterone levels have been correlated with more favorable cardiovascular risk factors, and supplementation with testosterone to bring older men into the normal range for healthy younger men appears to improve several cardiovascular risk factors, and may slow the progression of atherosclerosis.
The primary purpose of this study is to look at the effects of testosterone replacement on the progression of atherosclerosis in older men. This study is also being done to find out whether replacement with testosterone in older men with low testosterone levels improves their health-related quality of life.
|Hypogonadism Atherosclerosis||Drug: Testosterone Gel (Androgel) Drug: Placebo||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Testosterone Replacement on Atherosclerosis Progression in Older Men With Low Testosterone Levels|
- Change From Baseline in Common Carotid Artery Intima-Media Thickness (IMT) [ Time Frame: Baseline and Month 36 ]B-mode carotid artery images for IMT were acquired from the far wall of the distal centimeter of the right carotid artery with high-resolution ultrasound equipment. IMT is used as a predictor of the incidence of cardiovascular events. An increase in the IMT thickness is associated with a higher incidence of cardiovascular events. Less thickening is best. Change is expressed in millimeters (mm).
- Change From Baseline in Coronary Artery Calcium Score [ Time Frame: Baseline and Month 36 ]A multiple detector computed tomography (MDCT) scan was performed. Proximal coronary arteries were visualized, and at least 30 consecutive images were obtained at 3-mm intervals. Coronary calcium was defined as a plaque of at least 3 contiguous pixels (area, 1.02 mm^2) with a density of more than 130 Hounsfield units.The lesion score was calculated by multiplying lesion area by a density factor derived from Hounsfield units. The Agatston method was used to determine the total calcium score by summing the lesion scores from the left main, left anterior descending, circumflex, and right coronary arteries. The Agatston score is the measure of calcification in arteries expressed on continuous scale with "0" value (better) indicating no calcification and score above 400 (worse) indicating high calcification. There is no upper limit for this measure. A positive change from baseline indicates a worsening.
- Change From Baseline in Lipid Profiles [ Time Frame: Baseline and Month 36 ]Laboratory tests included in the lipid profile were Total Cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C) and Triglycerides.Lower values for Total Cholesterol, LDL-C are better and a negative change from Baseline indicates improvement. Higher values for HDL-C are better and a positive change from Baseline indicates improvement.
- Changes in Biomarkers of Inflammation [ Time Frame: Three years ]
- Changes in Blood Pressure [ Time Frame: Three years ]
- Change From Baseline in Complex Figure (Immediate) and Complex Figure (Delayed) [ Time Frame: Baseline and Month 36 ]Cognitive Function was assessed by Complex Figure (Immediate) and (Delayed). The Complex Figure Test consists of three tasks: copy, immediate recall, and delayed recall. Participants were presented with a complex design and then asked to draw the same figure. Subsequently, they were instructed to draw what they remembered immediately, and after a 30 minute delay. Scoring was based on the number of correct items for a total possible score of 0 (worst) to 36 (Best). A positive change from Baseline indicates improvement. A negative change from Baseline indicates a worsening.
- Change From Baseline in Paragraph Recall Test (Delayed) [ Time Frame: Baseline and Month 36 ]Cognitive Function was assessed by the Paragraph Recall Test (Delayed). In the Paragraph Recall Test, participants were read two short paragraphs and asked to recall them immediately and after a 30 minute delay, using the exact words that were read aloud. Scoring was based on the number of items correctly recalled. More items correctly recalled is best and a positive change from Baseline indicates improvement.
- Change From Baseline in the Buschke Selective Reminding Test (Delayed) [ Time Frame: Baseline and Month 36 ]Cognitive function was assessed by the Buschke Selective Reminding Test. In the Buschke Selective Reminding Test, participants were read 12 words and asked to recall as many words as possible. Subsequent trials included only those words that were not recalled in the preceding trial. Individuals were also asked to recall the list 30 minutes later. To assess phonemic and category fluency, participants were asked to name as many items from a given category as possible in 1 minute. Higher number of correct items is best and a positive change from Baseline indicates improvement.
- Change From Baseline in the Verbal Fluency Test [ Time Frame: Baseline and Month 36 ]Cognitive function was assessed by the Verbal Fluency Test. Participants were asked to name as many letters from a given category as possible in 1 minute. Higher number of letters is best and a positive change from Baseline indicates improvement.
- Change From Baseline in the Category Fluency Test [ Time Frame: Baseline and Month 36 ]Cognitive function was assessed by the Category Fluency Test. Participants were asked to name as many items from a given category as possible. Higher number of items named is best and a positive change from Baseline indicates improvement.
- Change From Baseline in the Stroop Interference Test [ Time Frame: Baseline and Month 36 ]Cognitive function was assessed by the Stroop Interference Test. In the Stroop Interference Test, participants were presented with a word list of colors printed in ink of a color different from how the printed word read. Participants were instructed to read aloud the color of the ink in which a word was printed, while not verbalizing the word itself. The time in seconds that the items were correctly identified was recorded. Less time is better and a negative change from Baseline indicates improvement.
- Change From Baseline in the Trail Making Test B [ Time Frame: Baseline and Month 36 ]Cognitive function was assessed by the Trail Making Test B. Trail Making Test B involved participants connecting numbers (1-13) and letters (A-L) alternately (1-A, 2-B, etc) on a piece of paper as quickly as possible. Scores represent the time it takes the participant to complete the test. Less time is best and a negative change from Baseline indicates improvement. A positive change from Baseline indicates a worsening.
- Change From Baseline in Chest Press Strength and Leg Press Strength [ Time Frame: Baseline and Month 36 ]Maximal voluntary strength of the lower and upper extremities was assessed using the one repetition maximum (1-RM) method for the seated leg press and chest press exercises. Participants were positioned with standardized seat position and foot placement that allowed 90° of knee flexion for the leg press exercise. Seat height and handle position was standardized for the chest press. Participants were familiarized with the exercises, practiced the technique and completed a 5-minute warm-up. The 1-RM procedure consisted of a warm up set with 5 to 8 repetitions at a resistance set to about 50% of the participant's estimated 1-RM and progressed with increasing loads interspersed with standardized rest periods until the participant was able to perform only one full-range-of-motion repetition.
- Change From Baseline in Unloaded Stair Climb Power and Loaded Stair Climb Power [ Time Frame: Baseline and Month 36 ]Physical Function was evaluated using two tests of stair climb power using an indoor 12-step staircase. One test consisted of ascending the 12-steps as rapidly as possible without running (unloaded stair climb) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags (loaded stair climb). Time to ascend the stairs was measured electronically with a digital clock and switch mats placed at the base of the steps and on the 12th step. Power in watts is calculated by the following: [body weight (kilograms) * distance (meters)/ (time/60)] /6.12. A negative change from Baseline indicates improvement.
- Change in Sexual Function as Assessed by the International Index of Erectile Function (IIEF) [ Time Frame: Baseline and Month 36 ]IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (6 questions), orgasmic function (2 questions), sexual desire (2 questions), intercourse satisfaction (3 questions), and overall sexual satisfaction (2 questions). Each question was answered on a 5-point scale from 1 to 5 (best) with a total possible score range of 0 to 75 with higher scores representing better function. A positive change from Baseline indicates improvement.
- Change in Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) [ Time Frame: Baseline and Month 36 ]The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL. The Overall Score is the average of the individual domain scores. A negative change from Baseline indicates improvement.
|Actual Study Start Date:||September 2004|
|Study Completion Date:||May 12, 2012|
|Primary Completion Date:||February 7, 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Testosterone
Participants received 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years. Dose adjustments were made by an unblinded observer. (Serum testosterone level measured on treatment day 15 was measured in a sample sent separately to the laboratory such that the results were reported directly to unblinded physician, who then communicated the decision about dose adjustment (or not) directly to the research pharmacist through e-mail.)
Drug: Testosterone Gel (Androgel)
7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years
Placebo Comparator: Placebo
Participants received placebo-matching testosterone gel daily for 3 years.
Placebo-matching testosterone gel daily for 3 years
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00287586
|United States, Arizona|
|Kronos Longevity Research Institute|
|Phoenix, Arizona, United States, 85016|
|United States, California|
|Charles R. Drew University of Medicine and Science|
|Los Angeles, California, United States, 90059|
|United States, Massachusetts|
|Boston University / Boston Medical Center|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Shalender Bhasin, MD||Boston University / Boston Medical Center, Boston, MA|