We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Testosterone Replacement in Older Men and Atherosclerosis Progression (TEAAM)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00287586
First Posted: February 7, 2006
Last Update Posted: June 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Solvay Pharmaceuticals
Information provided by (Responsible Party):
Shalendar Bhasin, MD, Brigham and Women's Hospital
  Purpose

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.


Condition Intervention Phase
Hypogonadism Atherosclerosis Drug: Testosterone Gel (Androgel) Drug: Placebo Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Shalendar Bhasin, MD, Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 308
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)
Arms Assigned Interventions
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.
Drug: Placebo
Placebo-matching testosterone gel daily for 3 years

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 60 years or greater
  • Hypogonadism, Testosterone 100-400 ng/dl or Free Testosterone < 50 pg/ml
  • Generally good health
  • At least 8 years of primary school education
  • Able to pass screening test for dementia
  • Able to give informed consent

Exclusion Criteria:

  • Testosterone level < 100 ng/dl (these individuals will be referred for evaluation of severe hypogonadism)
  • Use of testosterone or other androgens [dehydroepiandrosterone (DHEA), Androstenedione] in last year
  • Use of growth hormone in the last year
  • Current alcohol of drug dependence [Alcohol Use Disorders Identification Test (AUDIT) Score > 8]
  • Diseases known to affect gonadal function
  • Medications known to affect gonadal function eg. anticonvulsants, glucocorticoids such as prednisone
  • Prostate cancer, breast cancer
  • Any cancer that may limit life expectancy to less than 5 years
  • Limiting neuromuscular, joint or bone disease
  • History of stroke with residual neurologic deficit
  • Neurologic condition that would impair cognitive function including:

epilepsy, multiple sclerosis, human immunodeficiency virus (HIV), Parkinson's disease, stroke

  • Psychiatric disorder in the last year meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSMIV) Axis 1 criteria
  • Use of psychotropic medicine for at least 6 months
  • Dementia as assessed by (Telephone Interview for Cognitive Status modified score less than 31)
  • Severe symptoms of benign prostatic hyperplasia (BPH) (American Urological Association symptom index score greater than 21)
  • Prostate nodule or induration of digital rectal exam (DRE)
  • Prostate specific antigen (PSA) greater than 4 unless participant has had a negative transrectal biopsy within last 3 months
  • Limiting heart disease in including New York (NY) Class III or IV - congestive heart failure, unstable angina, or myocardial infarction (MI) in last 3 months
  • Liver function tests [aspartate aminotransferase (AST) and alanine aminotransferase(ALT)] greater than 3 times the upper limit of the reference range
  • Serum creatinine (Cr) greater than 2.5 mg/dl
  • Hematocrit greater than 48%
  • Hemoglobin (Hb)A1c greater than 9.0%
  • Untreated thyroid disease
  • Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg)
  • Body mass index (BMI greater than 35 kg/m2)
  • Untreated severe obstructive sleep apnea
  • Development of electrocardiogram (EKG) changes consistent with myocardial ischemia or changes in blood pressure during cardiopulmonary exercise testing will be excluded from testing of muscle strength and physical function.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00287586


Locations
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
Sponsors and Collaborators
Brigham and Women's Hospital
Solvay Pharmaceuticals
Investigators
Principal Investigator: Shalender Bhasin, MD Boston University / Boston Medical Center, Boston, MA
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shalendar Bhasin, MD, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00287586     History of Changes
Other Study ID Numbers: H-24192
First Submitted: February 6, 2006
First Posted: February 7, 2006
Results First Submitted: March 28, 2017
Results First Posted: June 29, 2017
Last Update Posted: June 29, 2017
Last Verified: May 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shalendar Bhasin, MD, Brigham and Women's Hospital:
Testosterone Replacement
Heart Disease
Vascular Disease
Risk Factors for Cardiovascular Disease
Cholesterol
Obesity
Blood pressure
Quality of Life

Additional relevant MeSH terms:
Atherosclerosis
Hypogonadism
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Gonadal Disorders
Endocrine System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents