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

Coronary Artery Disease Clinical Trial

Official title:

The Cardiac Benefit of Androgen Replacement in Hypogonadal Males With Coronary Artery Disease Following Successful Percutaneous Coronary Intervention (PCI).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413244
• Other study ID #: GCO 06-1081
• Status: Completed
• Phase: Phase 3
• First received: December 18, 2006
• Last updated: November 24, 2015
• Start date: January 2007
• Est. completion date: November 2014

Study information

• Verified date: November 2015
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: November 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• AndroGel 5 Grams
Placebo (randomization will occur on a 2:1 drug to placebo). A total of 50 subjects will be randomized to receive Androgel 5 grams and 25 subjects will be randomized to receive placebo. Androgel treatment/Placebo (after the treatment arm is assigned, subjects will be instructed to begin the study drug at 1 week post entry into the study and will continue to take the study drug for a total of 6 months. The study drug has to be applied to the skin once daily for 6 months.
• Placebo
Placebo (randomization will occur on a 2:1 drug to placebo). A total of 50 subjects will be randomized to receive Androgel 5 grams and 25 subjects will be randomized to receive placebo. Androgel treatment/Placebo (after the treatment arm is assigned, subjects will be instructed to begin the study drug at 1 week post entry into the study and will continue to take the study drug for a total of 6 months. The study drug has to be applied to the skin once daily for 6 months.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cardiac stress test	objective markers of cardiac disease following successful percutaneous coronary intervention (3 months after the procedure) for coronary artery disease as measured by cardiac stress test	at 6 months	No
Secondary	Seattle Angina Questionnaire (SAQ)	objective markers of cardiac disease following successful percutaneous coronary intervention (3 months after the procedure) for coronary artery disease as measured by cardiac stress test	at 6 months	No
Secondary	reactive hyperemia peripheral arterial tonometry (PAT)	Improve Endothelial function as measured PAT. Non-invasive tool to identify subjects with coronary endothelial dysfunction by measuring changes in digital pulse volume during reactive hyperemia.	at 6 months	No
Secondary	Improve Cardiac inflammatory markers		at 6 months	No
Secondary	Improve Metabolic syndrome-related parameters e)		at 6 months	No
Secondary	Improve Quality of life parameters		at 6 months	No
Secondary	Improve erectile function		at 6 months	No