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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00413244
First received: December 18, 2006
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Drug: AndroGel 5 Grams
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Cardiac Benefit of Androgen Replacement in Hypogonadal Males With Coronary Artery Disease Following Successful Percutaneous Coronary Intervention (PCI).

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • cardiac stress test [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Seattle Angina Questionnaire (SAQ) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    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

  • reactive hyperemia peripheral arterial tonometry (PAT) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    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.

  • Improve Cardiac inflammatory markers [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Improve Metabolic syndrome-related parameters e) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Improve Quality of life parameters [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Improve erectile function [ Time Frame: at 6 months ] [ Designated as safety issue: No ]

Enrollment: 139
Study Start Date: January 2007
Estimated Study Completion Date: January 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Androgel treatment

Androgel 5 grams

Androgel treatment - 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.

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 Comparator: Placebo
Placebo - 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.
Drug: 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.


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

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413244

Locations
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Mount Sinai School of Medicine
Abbott
Investigators
Principal Investigator: Mary Ann McLaughlin, MD Mount Sinai School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00413244     History of Changes
Other Study ID Numbers: GCO 06-1081
Study First Received: December 18, 2006
Last Updated: January 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Hypogonadal
coronary artery disease
percutaneous coronary intervention (PCI)

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on April 16, 2014