Clinical trial NCT00413244: The Cardiac Benefit of Testosterone Replacement in Men With Low Testosterone Levels With Coronary Artery Disease After Successful Intervention of the Blockage or Narrowed Heart Artery
Official title: The Cardiac Benefit of Androgen Replacement in Hypogonadal Males With Coronary Artery Disease Following Successful Percutaneous Coronary Intervention (PCI).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronary Artery Disease
Keywords: Hypogonadal
coronary artery disease
percutaneous coronary intervention (PCI)
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2006-12-19
Enrollment: 51
Sex: MALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to find out if giving the study drug, Androgel (testosterone) as a testosterone replacement help bring the testosterone to an acceptable level and to find out if it will help improve heart condition in males with coronary artery disease (CAD) following successful percutaneous coronary intervention.

Detailed description: Males with coronary heart disease have lower serum levels of bioavailable testosterone than men of a similar age with normal coronary angiograms (English, European Heart Journal, 2000). Low plasma testosterone has been associated with known risk factors for CHD, including age, obesity, hyperinsulinemia, diabetes, and adverse lipid profile.

Testosterone has also been shown in numerous studies to be a vasodilator. Recently, testosterone replacement compared with placebo, in hypogonadal men was shown to improve time to ischemic threshold, assessed by treadmill exercise testing at 4 and 12 weeks (Malkin, Heart, 2000). Prior studies had also shown a beneficial effect on exercise-induced ischemia in men with CAD, but not exclusively hypogonadal men (Jaffe,Br Heart J 1977; Rosano, Circulation, 1999; English, Circulation, 2000). In addition, this proposed study would be the first study to assess if the anti-anginal effects persists long term.

This is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of testosterone supplementation in hypogonadal men with coronary artery disease following successful revascularization with percutaneous coronary intervention (PCI). Only those men who had successful coronary artery revascularization, and on stable cardiac medical regimen for the prior 4 weeks will be included. Eligible patients will then be randomized on a 2:1 basis with 50 subjects receiving 5 grams of AndroGel and 25 subjects receiving placebo gel.

The men in this study who demonstrate hypogonadism represent a novel population to demonstrate the safety and efficacy of testosterone supplementation to improve cardiac function and outcomes. We hypothesize that treatment of hypogonadism in men with CAD, following successful PCI, will significantly improve cardiac ischemic threshold as assessed by cardiac stress testing. Furthermore, additional cardiac endpoints such as angina status, endothelial function and inflammatory serum markers will also demonstrate significant benefit in the testosterone treated group.

Eligibility criteria: Inclusion Criteria:

* Adult male patients with coronary artery disease (CAD) (one to three vessel diseased).
* Stable cardiac status at least 3 months after percutaneous coronary intervention (PCI).
* No change in cardiac medications for 4 weeks prior to enrollment.
* Testosterone \< 300 ng/dl or free testosterone \< 5.0 ng/dl or bioavailable testosterone \< 150 ng/dl.
* Sex Hormone Binding Globulin (SHBG) \< 7nmol/liter and Free Testosterone \< 50pg/dl
* Prostate Specific Antigen (PSA) \< 2.5 ng/mL or 2.6-3.7ng/mL with a negative prostate biopsy within the last 6 months and pathology report available for investigator's review.
* Subgroup of diabetics with well to moderately controlled diabetes (defined by a HgbA1c of \< 9mg/dL.

Exclusion Criteria:

* Hematocrit greater than 50%.
* Severe hypertension (exhibit systolic blood pressure \>180mmHg and diastolic blood pressure \>110 mmHg at baseline visit or a have a history of malignant hypertension.
* Significant cardiac arrhythmia (supraventricular tachycardia \[SVT\] or ventricular tachycardia with heart rate exceeding 110 beats per minute at Visit 1).
* ECG abnormalities precluding ST segment analysis on treadmill, or inability to walk on treadmill.
* Poorly controlled, symptomatic, active medical problems (HIV, hepatitis, cancer, benign prostatic hypertrophy, alcohol or drug abuse, major depressive disorder).
* Neurological or psychiatric disorder that would compromise the patient's ability to give informed consent or adhere to the requirements of the protocol.
* History of prostate cancer
* History of hypersensitivity to transdermal testosterone gel.
* International Prostate Symptom Score (IPSS) \>19 at Visit 1.

Primary outcomes:
measure: Cardiac Stress Test: Time to ST Depression
timeFrame: at 6 months
measure: Cardiac Stress Testing: Exercise Capacity
timeFrame: At 1 month, 3 months, and 6 months
Secondary outcomes:
measure: Seattle Angina Questionnaire (SAQ)
timeFrame: up to 6 months
measure: Reactive Hyperemia Index
timeFrame: 6 months
measure: International Prostate Symptom Score (IPSS)
timeFrame: 6 months
measure: Metabolic Equivalents of Task (METS)
timeFrame: 6 months
measure: Aging Male Symptoms (AMS)
timeFrame: At baseline, 1 month, 3 months, and 6 months
measure: International Index of Erectile Function (IIEF)
timeFrame: At baseline, 1 month, 3 months, and 6 months
measure: IIEF-II Orgasmic Function
timeFrame: At baseline, 1 month, 3 months, and 6 months
measure: IIEF -III: Sexual Desire
timeFrame: At baseline, 1 month, 3 months, and 6 months
measure: IIEF-IV: Intercourse Satisfaction
timeFrame: At baseline, 1 month, 3 months, and 6 months
measure: IIEF-V: Over-all Satisfaction
timeFrame: At baseline, 1 month, 3 months, and 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Mary Ann McLaughlin, MD
role: PRINCIPAL_INVESTIGATOR
References: