The Effect of GHRH Therapy on Myocardial Structure and Function in Congestive Heart Failure

PP1- The overall purpose of this study is to evaluate the effects of Growth Hormone
Releasing Hormone (GHRH) on cardiac structure and function in subjects aged 50 years and
older with a diagnosis of congestive heart failure in a single blinded (to the subject)
randomized treatment/placebo study design. They will receive 12 weeks of drug or placebo, 6
weeks of washout, and 12 weeks of placebo or drug- whichever they didn't receive in the
first 12 weeks. The hypotheses are: 1)normal aging is associated with evidence of declining
somatotrophic activity exemplified by IGF-1 levels; 2) GHRH can raise levels of Growth
hormone and IGF-1 in elderly individuals in a dose dependent fashion with minimal
deleterious side effects; 3) GHRH will produce measurable increments in myocardial
performance and structure and demonstrated growth of peripheral musculature; 4) the
combination of these benefits will result in better quality of life due to the improvement
of overall cardiac function.

INCLUSION CRITERIA:

- subjects will be at least 50 years of age,

- women who are post-menopausal.

- clinical evidence of congestive heart failure, with ongoing management by
conventional medical therapy

- a left ventricular ejection fraction below 40% as measured by echocardiogram
performed within 6 months of study enrollment.

- Left ventricular end-diastolic dimension greater than 60 mm as measured by an
echocardiogram performed within 6 months of study enrollment.

- regular heart rate/pacer

- hemodynamically stable and able to complete symptom-limited bicycle ergometry
exercise test;

- and be in New York Heart Association Classification II or III.

EXCLUSION CRITERIA:

- Subjects with hematocrit equal to or less than 33%;

- body mass index equal to or greater than 40;

- unstable angina within six months;

- inducible ischemia by exercise stress testing, radionuclide scintigraphy, or
dobutamine echocardiography;

- known or suspected myocarditis;

- known or suspected restrictive or infiltrative cardiomyopathy;

- coronary artery stenosis >70% and < 100% by catheterization should such data be
available;

- inadequate cardiac echo window;

- primary diastolic dysfunction in heart failure

- inability to perform cycle ergometry;

- critical aortic stenosis;

- severe mitral regurgitation by Doppler echocardiography;

- uncontrolled or poorly controlled hypertension;

- hypertrophic cardiomyopathy;

- renal failure, determined by creatinine > 2.0.

- untreated thyroid disease;

- active alcoholism,

- breast cancer;

- prostate cancer;

- inability to provide informed consent;

- uncontrolled hyperlipidemia; (Triglycerides >1200 and/or LDL > 160)

- patients with known bleeding disorders;

- patients using atropine, artane, scopolamine, and cogentin.

- Subjects who have implanted devices that contain metal and are not adherent to the
body will be excluded from the MRI testing in this study. These devices include
pacemakers, implanted ICD's, infusion pumps, nerve stimulators, metal debris in the
eye, or loose metal, such as shrapnel or a bullet.

- Inability to lie flat on back for an extended period of time. The MRI testing
requires this posture.

- History of any noncutaneous malignancy within 5 years of screening.

STUDY TERMINATION CRITERIA:

The following clinical events will define drop-points for worsening clinical conditions
and will terminate subject involvement in the study:

- Unstable angina

- Acute myocardial infarction (chest pain with EKG changes and increased troponin)

- NYHA Class IV heart failure for greater than one week (a brief episode of NYHA Class
IV heart failure may result from medical or dietary indiscretion, adverse effects of
non-study medications, poorly controlled hypertension and other potentially
reversible mechanisms)

- Documented sustained ventricular tachycardia

- Resuscitated cardiac arrest

- Unexplained syncope

- Diagnosis of sleep apnea that is not medically supervised.

- Symptomatic documented bradycardia

- Diagnosis of a new non-cutaneous malignancy

- Developing exclusion criteria

- Stroke

- Death