Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Sequential Clinical Trial of Sodium Valproate in ALS|
- The rate of decline of daily functioning
|Study Start Date:||April 2005|
|Study Completion Date:||February 2007|
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by progressive degeneration of motor neurons leading to muscle weakness.
The pathogenesis of ALS is unknown, but there is convincing evidence that several molecular mechanisms play a role. Previous studies investigated the role of the Survival Motor Neuron (SMN) gene in ALS. Recent data suggest that SMN genotypes producing less SMN protein increase susceptibility and severity of ALS. This leads to the hypothesis that the clinical expression of ALS is influenced by the total SMN protein level in affected patients. In a population of ALS patients in the Netherlands we found that SMN genotypes producing less SMN protein appear to increase susceptibility and severity of ALS. It was shown that the HDAC inhibitor sodium valproate (SVP) increases levels of SMN protein in vitro. From these results and from data suggesting neuroprotective properties of SVP, it is hypothesised that SVP could extend survival of patients with ALS. In addition, sodium valproate significantly prolonged the disease duration in the animal model for ALS, the SOD1 transgenic mouse. Given that SVP is a FDA-approved compound with well-known pharmacokinetic and toxicity profiles, it is an attractive candidate for a clinical trial in ALS patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00136110
|Utrecht, Netherlands, 3584 CX|
|Study Chair:||Leonard H Van den Berg, MD, PhD||UMC Utrecht|
|Principal Investigator:||Sanne Piepers, MD||UMC Utrecht|
|Principal Investigator:||Sonja W De Jong, MD||UMC Utrecht|