PLAN FOR A TRIAL OF DHEAS IN MYOTONIC DYSTROPHY

University Of Rochester, Rochester NY

Investigators

Abstract

DESCRIPTION (Taken from the application): There is still no effective treatment that improves or even slows the progressive muscle wasting and weakness that occur in myotonic dystrophy (dystrophica myotonia, DM), the most common inherited muscle disease in adults. Despite the 'discovery of the gene lesion in 1992, no specific therapy has been found. However, encouraging results of recent trials with dehydroepiandrosterone sulfate (DHEAS) have given hope that a helpful treatment may be available. An open-label study of daily intravenous DHEAS in patients with DM has reported an improvement in muscle strength and a decrease in myotonia (Sugino et al, 1998). In addition, preliminary results from our pilot studies at the University of Rochester suggest that oral DHEAS is safe and well tolerated and that it may improve both the quality of life and the neuropsychological alterations in patients with DM. The duration and reproducibility of these different beneficial effects remain to be determined, and the possible mechanisms responsible need to be identified. However certain actions are likely to have contributed to the improvement. Circulating levels of DHEA and DHEAS are markedly reduced in patients with DM. Therapy restoring DHEAS to normal levels may have produced trophic effects on skeletal muscle, as it has in other situations in which DHEA/S are deficient. The pharmacologic doses of DHEA used, may also have increased the circulating levels of IGF-l, the principal growth factor that stimulates muscle growth and repair. To evaluate and to substantiate these encouraging results of DHEAS therapy, 7 participating centers of the Muscle Study Group (MSG) have initiated plans for a multi-center, double-blind, randomized trial of DHEAS in patients with DM. This application requests support for final planning of this multi-center trial. We plan to determine if daily DHEAS treatment improves strength, reduces myotonia, enhances quality of life and ameliorates alterations in neuropsychological function. Patients will be recruited at the 7 MSG Centers and will receive either physiologic or pharmacologic doses of DHEAS or placebo. Extensive collaboration between these MSG Centers in other therapeutic trials has occurred over the past 3 years. We are confident that we can design an optimal study and carry it out appropriately. We have also obtained the assistance of The Clinical Trials Coordination Center of the University of Rochester which will help us develop plans for data management and oversight of the trial. Our planning process will result in a final protocol for the randomized trial, consent form, data collection forms, Manual Of Operations and Procedures, and an infrastructure to support our future application to NIAMS for funding to conduct the anticipated randomized trial.