GHRH Therapy and Myocardial Structure &Function in CHF

Massachusetts General Hospital, Boston MA

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Linked publications & trials

Abstract

GRANT=6446812;P01AG Normal aging is associated with a high prevalence of declines in muscle mass and function. Disease and disuse compound these changes. Recent evidence suggests that quantitative and functional improvements can be made through several modalities addressing sarcopenia. The prime hormonal stimulus for lean body mass growth is growth hormone (GH). Studies of aging populations suggest that feedback inhibition on GH or lack of stimulation by growth hormone releasing hormone (GHRH) results in a high prevalence of sarcopenia secondary to GH, insulin-like growth factor I (IGF-I) and its counterpart. Recent evidence links growth hormone deficient states with decrements in myocardial and cardiovascular function that can be improved with GH administration. Congestive heart failure (CHF), prevalent and morbid in the aging population, has been shown to be responsive to the administration of GH. Unfortunately, toxicity of GH and IGF-I, given directly, has limited their therapeutic use. GHRH activates the GH cascade of somatotrophic effects in a coordinated and, to date, less toxic fashion. The recent availability of GHRH creates an ideal opportunity to physiologically examine the effectiveness of restoring somatotrophic function and targeting an illness most common in the elderly-CHF and the associated peripheral muscle loss and function. The overall purpose of this study is to evaluate the effects of GHRH on exercise performance and quality of life in volunteers aged 65 years and older with a diagnosis of congestive heart failure in a double-blinded, randomized treatment/placebo 6-month study. Outcome measures will be self-perceived quality of life, exercise performance, cardiac mass, lean body mass and strength, and increased expression of IGF-I and decreased expression of myostatin in peripheral muscle. The hypotheses are: a) trophic hormone releasing factor administration (GHRH) will collect the endocrinology of aging (low GH and IGF-I levels) in a safe and quantifiable fashion; b) correct trophic factor levels (GH, IGF-I) result in improved tissue structure and function in older patients with dilated cardiomyopathy; c) the restoration of tissue trophism to normal is mechanistically linked to fundamental changes in cardiac and peripheral muscle.