HEART-MEND: Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Completed

CT.gov ID

NCT01190904

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

568

Enrollment

Locations

Duration (Months)

113.6

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if androgen deficiency (low levels of testosterone, a male hormone produced by the sex glands) and erectile dysfunction (sexual dysfunction) will predict over time the development of a heart attack, stroke, or death in men with Diabetes Mellitus who have angiographically proven coronary artery disease (CAD) (≥50%) with or without percutaneous coronary intervention (PCI). A substudy aims to show the different factors and processes that may show a relationship between sexual function and levels of androgen in the body to heart disease.

Condition or Disease	Intervention/Treatment	Phase
Androgen Deficiency AD Erectile Dysfunction ED Diabetes Mellitus Coronary Artery Disease Coronary Revascularization

Detailed Description

Diabetes mellitus (DM) and multi-vessel coronary artery disease (CAD) entail significant risk for progression of cardiac morbidity and mortality. Compelling recent research points to biological pathways that link DM and CAD to androgen status and sexual function. We hypothesize that androgen deficiency (AD) and erectile dysfunction (ED) independently serve as sentinel indicators, predicting the future development of adverse cardiovascular and cerebrovascular events in men with diabetes following coronary revascularization.

ED is emerging as a barometer of overall endothelial function. We hypothesize that as a consequence of this relationship, erectile dysfunction is predictive of cardiovascular outcomes in men with diabetes and CAD. We also propose that AD affects morbidity and mortality in men with DM and CAD by influencing presentation and progression of endothelial dysfunction as well as inflammation and hemostasis.

We propose to investigate four specific aims using 1,143 diabetic men who have angiographically proven coronary artery disease (CAD) (≥50%) in at least one major epicardial vessel with or without percutaneous coronary intervention (PCI). Specific aims of this study are: 1) To determine whether androgen status at baseline independently predicts primary and secondary endpoints in men (n=1,143) with DM and CAD. 2) To determine whether erectile dysfunction at baseline independently predicts cardiovascular outcomes in men with DM and CAD. 3) To determine whether change of androgen status and sexual function over time independently predict cardiovascular outcomes in men with DM and CAD. 4) To demonstrate specific mediators and pathways that link sexual function and androgen status to cardiovascular disease.

The primary endpoint is defined as the combined all-cause mortality, non-fatal myocardial infarction (MI), and stroke. Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6 months, 12 months, 18 months, 24 months, 30 months and 36 months following catheterization.

Study Design

Study Type:

Observational

Actual Enrollment :

568 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Coronary Artery Disease (≥50%) with or without PCI We propose to investigate four specific aims using 1,143 diabetic men who have CAD (≥50%) lesion in at least one major epicardial vessel with or without PCI.

Outcome Measures

Primary Outcome Measures

Composite outcome of all-cause mortality [up to 3 Years]
The primary outcome is time to composite outcome of all-cause mortality, MI or stroke.

Secondary Outcome Measures

To determine whether androgen status at baseline independently predicts primary and secondary endpoints in men (n=1,143) with DM and CAD. [Baseline]
Androgen profile consists of total, free, and bio-available testosterone (T) and testosterone:estradiol ratio. Hypothesis: AD at baseline (defined by total T < 300 ng/dl) will be an independent predictor of primary and secondary outcomes.
To determine whether erectile dysfunction at baseline independently predicts cardiovascular outcomes in men with DM and CAD. [Baseline]
ED severity will be determined using the International Index of Erectile Function (IIEF), a standard instrument that is available in multiple translations and has excellent cross-cultural validity. Hypothesis: Severe ED at baseline (IIEF < 11), while controlling for demographic and clinical covariates, will be an independent predictor of primary and secondary cardiac outcomes.
MACCE [at 6 months following catheterization]
Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6, 12, 18, 24, 30 and 36 months following catheterization.
MACCE [at 12 months following catheterization]
Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6, 12, 18, 24, 30 and 36 months following catheterization.
MACCE [at 18 months following catheterization]
Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6, 12, 18, 24, 30 and 36 months following catheterization.
MACCE [at 24 months following catheterization]
Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6, 12, 18, 24, 30 and 36 months following catheterization.
MACCE [at 30 months following catheterization]
Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6, 12, 18, 24, 30 and 36 months following catheterization.
MACCE [at 36 months following catheterization]
Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, nonfatal MI, stroke or revascularization at one year and angina status as evaluated with the Seattle Angina Questionnaire (SAQ) at 6, 12, 18, 24, 30 and 36 months following catheterization.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Male age [18-75 years];
Type 2 Diabetes, defined according to the American Diabetes Association as history of:

presence of classic symptoms of DM with unequivocal elevation of plasma glucose (2-hour post-prandial or random of >200 mg/dL (11mmol/L), b) fasting plasma glucose elevation on more than 1 occasion of at least 126 mg/dL (7mmol/L) or c) HA1C > 6.5, currently undergoing pharmacological or non-pharmacological treatment;

Angiographically confirmed Coronary Artery Disease (≥50%) with or without PCI;
Indication for revascularization based upon symptoms of angina and/or objective evidence of myocardial ischemia;
Willingness to comply with all follow-up required study visits; and
Signed and received copy of informed consent

Exclusion Criteria:

Severe congestive heart failure (class III or IV according to NYHA, or pulmonary edema) at the time of enrollment;
Previous stroke within 6 months;
Prior history of significant bleeding (within the previous 6 months) that might be expected to occur during PCI/DES related anticoagulation;
Acute ST-elevation MI (Q-wave) within 72 hours prior to enrollment requiring revascularization;
Abnormal creatine kinase (CK > 2x normal); or abnormal CK-MB levels at time of randomization;
Contraindication to either CABG or PCI/DES because of a coexisting clinical condition];
Significant leukopenia, neutropenia, thrombocytopenia, anemia, or known bleeding diathesis;
Intolerance or contraindication to aspirin or both clopidogrel and ticlopidine;
Dementia with a Mini Mental Status Examination (MMSE) score of <20;
Extra-cardiac illness that is expected to limit survival to less than 5 years (e.g. oxygen-dependent chronic obstructive pulmonary disease, active hepatitis or significant hepatic failure, severe renal disease);
Geographically inaccessible for follow-up visits required by protocol.
Additional Ancillary Study Exclusions. Exclusion criteria that are unique to the proposed study are prior use of hormonal therapy (HRT) with testosterone in men at baseline and current use of sex-hormone antagonist medications at baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hudson Heart Group	Guttenberg	New Jersey	United States	07093
2	Elmhurst Hospital	Elmhurst	New York	United States	11373
3	Winthorp University Hospital	Mineola	New York	United States	11501
4	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
5	Stony Brook University Hospital	Stony Brook	New York	United States	11794