Efficacy of Riluzole in Hereditary Cerebellar Ataxia
Condition: Cerebellar Ataxia
MeSH terms: Ataxia; Cerebellar Ataxia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The hereditary cerebellar ataxias include diverse neurodegenerative disorders. Hereditary
      ataxias can be divided into autosomal dominant ataxias (ADCAs), autosomal recessive ataxias
      (ARCAs), X-linked, and mitochondrial ataxias on the basis of mode of inheritance. The key
      feature in all these disorders is ataxia typically characterised by poor balance, hand
      incoordination, postural or kinetic tremor, dysarthria and dysphagia.

      To date no treatment has been shown to slow progression of the disease and symptomatic
      therapies are limited to few options that are partially effective.

      Purkinje cells project inhibitory signals to the deep cerebellar nuclei(DCN) which have a
      critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in
      the absence of synaptic input from Purkinje neurons and modulation of the DCN response by
      Purkinje input is believed to be responsible for coordination of movement, while uncontrolled
      spontaneous firing of DCN neurons may underlay cerebellar ataxia. Recent studies have
      demonstrated that small-conductance calcium-activated potassium (SK) channels inhibitor are
      able to increase DCN firing rate. Since SK channels are critical regulators of DCN firing
      rate, SK openers such as the drug riluzole may reduce neuronal hyperexcitability and thereby
      be useful in the therapy of cerebellar ataxia.

      On this base the investigators published a pilot study in patients with chronic cerebellar
      ataxia (Ristori et al., Neurology 2010) investigating safety and efficacy of riluzole or
      placebo administration for 8 weeks. The results demonstrated a significative improvement in
      International Cooperative Ataxia Rating Scale (ICARS) global score after four weeks and after
      8 weeks in the riluzole arm.

      The present protocol is aimed at verifying the safety and efficacy of riluzole administration
      for a longer period, in a larger sample size of patients, with more stringent diagnostic
      criteria (hereditary cerebellar ataxia), respect to the above pilot study. Sixty patients
      will be enrolled in a double-blind, placebo-controlled trial. By central randomisation,
      patients will take 50 mg of riluzole or placebo twice daily for 12 months. Treatment effects
      will be assessed by comparing the Scale for the Assessment and Rating of Ataxia (SARA) before
      treatment and during therapy at months 3 and 12.
    


Intervention name(s): riluzole; Placebo comparator
Intervention type(s): Drug; Drug
Intervention description(s): Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.; Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other intervention name(s): Rilutek; Placebo
Intervention MeSH terms: Riluzole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Spinocerebellar ataxia; Friedreich ataxia