This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This is a multi-center phase II trial of an combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA 'sitters' 2-8 years of age. Cohort 2 is an open label protocol for SMA 'standers and walkers' 3-17 years of age to explore responsiveness of efficacy outcomes. Outcome measures will include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL(tm) assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. We will also request consent to establish a DNA and cell line resource on each patient, their parents and siblings is applicable for future genetic studies. Such studies may be critical in identifying features which predict 'responders' from 'non-responders', and assist in the identification of genetic modifier loci with potentially important future therapeutic applications. Additional information regarding tolerability and efficacy of these drugs in these SMA populations will be important in guiding future trial design. A Medical Monitor will review parameters for drug toxicity and a Data Safety and Monitoring Committee will protect subjects' safety. Six centers will enroll a total of 90 patients.
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