VALIANT Clinical Trial of Ambulatory Type III Spinal Muscular Atrophy Patients Conducted at Ohio State University Published in Muscle and Nerve

Originally published on May 21, 2013.

Results from the Phase II Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANT SMA) clinical trial led by Dr. John Kissel at The Ohio State University have been published in the journal Muscle & Nerve. This study was funded by Cure SMA. The study was a randomized, prospective, placebo-controlled clinical trial designed to test the efficacy and safety of the combined treatment of valproic acid in ambulatory adults with type III SMA.  Overall results showed that VPA was not effective in improving strength or function in this population. The trial did demonstrate that the outcomes used in this study were reliable and could be employed in future trials in adults with SMA. The trial was registered at with identifier: NCT00481013.

Much basic and clinical evidence has suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA), including an open label trial of VPA in ambulatory SMA adults, showing  VPA markedly improved strength in this population.  The clinical trial network Project Cure SMA conducted the 12-month, double blind clinical trial of VPA in ambulatory adults with SMA to test this idea.

The study involved 33 genetically proven type III adult SMA subjects age 20-55 years.  Subjects underwent baseline assessments and then were randomized to receive VPA or placebo.  At six months, patients were switched to the other group in a cross over design. The primary outcome was the six-month change in muscle strength.  There were multiple secondary outcomes, including changes in hand held dynamometry, ulnar compound muscle action potential amplitudes (CMAP) assessing motor neuron function, timed function tests of stair-climbing and the six-minute walk test, pulmonary function, muscle mass, a quality of life scale, and an SMA modified Functional Rating Scale.

Thirty subjects completed the study and were analyzed. VPA was well tolerated and compliance was good. There was no significant change in any outcome at six or 12 months. Thus, VPA was not effective in improving strength or function in ambulatory SMA adults, which is consistent with the results from the two CARNIVAL Clinical Trials assessing efficacy of valproic acid in  type II/II and type I SMA patients. The outcomes used in this study were shown to be feasible and reliable, and can be employed in future trials in adults with SMA.

The trial has afforded investigators the opportunity not only to assess the efficacy and safety of this drug treatment, but also to test a number of new clinical trial outcome measures which are essential to conducting successful SMA trials, particularly in adults with SMA.  As Dr. Kissel noted, “This is one of only a handful of clinical trials in SMA that has focused exclusively on the adult SMA population, a group that has received relatively little attention in the past. We expect, however, that the data we generate will also prove useful in devising and testing therapies for patients with other types of SMA.  We are deeply appreciative of our patients who took the time to participate in the study, as we had patients from all over the country.”

Cure SMA has invested $6 million for the development of clinical trial infrastructure, including testing protocols and clinical trial site readiness. Cure SMA funding to Ohio State University has included three clinical trials and the establishment of a care clinic geared towards infants with SMA type I.

This funding paved the wave for the current major investment in SMA clinical trials by NIH. The NINDS has created The Network for Excellence in Neuroscience Clinical Trials, abbreviated NeuroNext.  NeuroNEXT is twenty-five site national clinical trial network created by NINDS of the NIH to test promising new therapies for both pediatric and adult patients with neurological diseases. Their first study is a SMA Biomarker Study in infants with SMA to be conducted at 15 NeuroNEXT Network sites around the United States. Stephen Kolb, MD, PhD of Ohio State University is the Protocol Principal Investigator for the study.

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