Idiopathic dilated cardiomyopathy in children is a rare disorder that is usually progressive despite current available therapies. Cardiac transplantation remains the only current prospect for dramatically improving survival in many patients. Recently, growth hormone (GH) therapy has been shown to induce myocyte growth and enhance the efficiency of myocardial energy metabolism. We propose to obtain preliminary data on the efficacy, as well as safety and tolerability, of GH in improving myocardial function in children with dilated cardiomyopathy. Our goals will be pursued in a prospective, single-center, randomized, partially-blinded crossover trial in children with idiopathic dilated cardiomyopathy of at least six months duration. Patients will be randomly assigned to receive initial therapy with either GH (0.3 mg/kg/week divided into daily doses) plus conventional therapy versus conventional therapy alone. After treatment for 6 months, patients will cross over to the opposite treatment regimen for a period of 6 months. Finally, children treated with GH during the second 6 month block will be followed off GH therapy (i.e., on conventional therapy alone) for an additional 6 months.
Specific Aim 1 is to assess the absolute changes in outcomes from baseline to 6 months after initiation of GH therapy. The primary outcome variable will be the change in shortening fraction, assessed by echocardiography. Secondary outcome variables will include changes in the following parameters: a) Measures of left ventricular function, assessed using echocardiographic techniques, including change in rate- corrected velocity of fiber shortening, left ventricular mass, mass-volume ratio, left ventricular shape (degree of eccentricity), wall stress, and stress-velocity, index. b) Measures of functional status, including anaerobic threshold, assessed by exercise testing, and parent perception of functional status, assessed by score on the parent report of the Child Health Questionnaire. If GH does result in improved myocardial function, Specific Aim 2 will be to assess the effect of duration of such therapy on changes in fractional shortening and on secondary measures of left ventricular function. Similarly, to assess carryover effects, we will analyze the slope with which these parameters deteriorate after discontinuation of GH therapy. This goal will be accomplished by serial measurements of echocardiographic parameters at baseline; at one, three, and six months after institution of GH therapy; and then at one, three, and six months after its discontinuation.
Specific Aim 3 will be to describe adverse side effects related to administration of GH in this population of children with idiopathic dilated cardiomyopathy. Adverse effects will be assessed at multiple time points within and after the period of GH administration. We hypothesize that GH therapy will have a very low rate of adverse effects in our study population, based upon its excellent safety profile when used in other pediatric populations with normal levels of endogenous GH. Inferences reached in this study may be broadly applicable to other, secondary forms of dilated cardiomyopathy.
| McElhinney, Doff B; Colan, Steven D; Moran, Adrian M et al. (2004) Recombinant human growth hormone treatment for dilated cardiomyopathy in children. Pediatrics 114:e452-8 |
