Cardiac MRI in Measuring the Impact of Anti-androgen Treatment on Cardiac Function in Patients With Prostate Cancer

PRIMARY OBJECTIVES:

I. Determine the impact of a minimum of 4 months of full androgen deprivation therapy (ADT)
on cardiac and skeletal muscle structure and performance using novel cardiovascular magnetic
resonance (CMR) approach.

OUTLINE:

Study participants will undergo a treadmill stress CMR focused on cardiac muscle comprised of
resting MRI over 10-15 minutes followed by treadmill exercise until peak stress. Patients
then undergo MRI and gadopentetate dimeglumine (Gd-diethylenetriamine penta-acetic acid
[DTPA]) perfusion imaging immediately after exercise and after a 6-8 minute recovery period.
Within 24 hours of treadmill CMR exam, patients also undergo skeletal muscle phosphorus
magnetic resonance spectroscopy (PMRS) while at rest, during, and in the recovery phase of
resistive lower extremity exercise which patients complete over 30 seconds. Both procedures
are performed before initiation of ADT treatment (baseline) and 4-7 months after initiation
of ADT treatment.

Inclusion Criteria:

- Have biopsy proven carcinoma of the prostate

- Be planning to begin a course of at least 4 months of ADT; the ADT is defined as: (a)
surgical castration; (b) gonadotropin-releasing hormone (GNRH) antagonist alone; (c)
GNRH antagonist with oral androgen receptor blockade, and (d) GNRH antagonist, oral
androgen receptor blockade, and 5-alpha reductase inhibitors; we will not include men
with only oral anti-androgen therapy such as 5-alpha reductase inhibitors alone or
oral anti-androgens alone

- Have an ECOG (Eastern Cooperative Oncology Group) performance status of 0-1

- Have plasma total cholesterol < 200 mg/dL

- Have plasma triglycerides < 200 mg/dL

- Have BUN/Cr (Blood urea nitrogen and serum creatinine) without clinically significant
abnormalities after review by the study physicians

- Liver enzymes without clinically significant abnormalities after review by the study
physicians

- CBC (complete blood count) without clinically significant abnormalities after review
by the study physicians

- PT/PTT/INR (prothrombin time/partial thromboplastin time) without clinically
significant abnormalities after review by the study physicians

- Voluntarily agree to participate and sign an informed consent document

Exclusion Criteria:

- Have an active malignancy other than prostate cancer that requires therapy

- Not be undergoing evaluation and workup for active cardiovascular disease; men with
treated and stable cardiovascular disease may participate

- Have plasma total cholesterol > 200 mg/dL or plasma triglycerides > 200 mg/dL

- Have a calculated glomerular filtration rate (GFR) =< 30 mL/min/1.73 m^2

- Are not free of unstable angina, arrhythmia, or severe systemic disease that would
make moderate intensity exercise participation unsafe

- Have any contra-indications to magnetic resonance (MR) examination such as allergy to
MRI contrast media (gadolinium-DTPA [gadopentetate dimeglumine]), metallic foreign
objects within the body, orbital metal, cerebral aneurysm clip, pacemaker,
defibrillator, neurostimulator, any other medical metallic implant, claustrophobia,
inability to lie flat for 30 minutes, and weight exceeding 300 pounds; if an MR
contraindication is discovered during scanning that was overlooked during the
screening process, the procedure will be stopped immediately and the subject will be
removed from the scanner

- Are receiving any form of renal replacement therapy or have a calculated glomerular
filtration rate (GFR) < 30 mL/min/1.75 m²; results of serum creatinine testing will be
reviewed for calculation of glomerular filtration rate (GFR); patients without a serum
creatinine level drawn within the prior 3 months will have this drawn upon enrollment

- Have uncontrolled hypertension and resting blood pressure exceeding 140/80 mmHg

- In addition, subjects with any contraindications to exercise testing according to
American Heart Association guidelines will not be enrolled; nonetheless, the
cardiovascular magnetic resonance (CMR) cardiologist supervising the research portion
of the exam will also evaluate each subject for evidence of any contra-indications;
the absolute contra-indications include acute myocardial infarction, high-risk
unstable angina, uncontrolled cardiac arrhythmias, active endocarditis, symptomatic
severe aortic stenosis, decompensated symptomatic heart failure, acute pulmonary
embolus or pulmonary infarction, acute non-cardiac disorder that may be aggravated by
exercise, acute myocarditis or pericarditis, physical disability that would preclude
safe and adequate test performance, and inability to provide consent; the relative
contra-indications include left main coronary stenosis, moderate stenotic valvular
heart disease, electrolyte abnormalities, tachyarrhythmias or bradyarrhythmias, atrial
fibrillation with uncontrolled ventricular rate, hypertrophic cardiomyopathy, and
high-degree atrioventricular node block; subjects with uncontrolled hypertension and
resting blood pressure exceeding 140/80 mmHg will be excluded