Riluzole for treating spasticity in patients with chronic traumatic spinal cord injury: Study protocol in the phase ib/iib adaptive multicenter randomized controlled RILUSCI trial

Abstract

Background Satisfactory treatment is often lacking for spasticity, a highly prevalent motor disorder in patients with spinal cord injury (SCI). Low concentrations of riluzole potently reduce the persistent sodium current, the post-SCI increase in which contributes to spasticity. The repurposing of this drug may therefore constitute a useful potential therapeutic option for relieving SCI patients suffering from chronic traumatic spasticity. Objective RILUSCI is a phase 1b–2b trial designed to assess whether riluzole is a safe and biologically effective means of managing spasticity in adult patients with traumatic chronic SCI. Methods In this multicenter double-blind trial, adults (aged 18–65 years) suffering from spasticity after SCI (target enrollment: 90 participants) will be randomly assigned to be given either a placebo or a recommended daily oral dose of riluzole for two weeks. The latter dose will be previously determined in phase 1b of the study by performing double-blind dose-finding tests using a Bayesian continuous reassessment method. The primary endpoint of the trial will be an improvement in the Modified Ashworth Score (MAS) or the Numerical Rating Score (NRS) quantifying spasticity. The secondary outcomes will be based on the safety and pharmacokinetics of riluzole as well as its impact on muscle spasms, pain, bladder dysfunction and quality of life. Analyses will be performed before, during and after the treatment and the placebo-controlled period. Conclusion To the best of our knowledge, this clinical trial will be the first to document the safety and efficacy of riluzole as a means of reducing spasticity in patients with chronic SCI. Trial registration The clinical trial, which is already in progress, was registered on the ClinicalTrials.gov website on August 9, 2016 under the registration number NCT02859792. Trial sponsor Assistance Publique–Hôpitaux de Marseille.