Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
Condition: Hereditary Ataxia; Multiple Sclerosis; Cerebellar Ataxia
MeSH terms: Multiple Sclerosis; Ataxia; Cerebellar Ataxia; Spinocerebellar Degenerations
Study type: Interventional
Phase: Phase 2

Summary: 
      Cerebellar disorders are often disabling and symptomatic therapies are limited to few options
      that are partially effective. It seems therefore appropriate to search for additional
      approaches.

      Purkinje cells are the sole output of the cerebellar cortex: they 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. Recent evidences support the notion that an
      increase in DCN excitability may be an important step in the development of cerebellar ataxia
      and point to the underlying molecular mechanisms: the inhibition of small-conductance
      calcium-activated potassium (SK) channels, that causes an increase of the firing frequency in
      DCN, correlates with cerebellar ataxia.

      The rationale of the present project is that SK channel openers, such as riluzole, may have a
      beneficial effect on cerebellar ataxia.

      The researchers propose to perform a pilot study investigating safety and efficacy of
      riluzole, an approved treatment for amyotrophic lateral sclerosis, as a symptomatic approach
      in patients with chronic cerebellar ataxia.
    

Detailed description: 
      Forty patients with chronic cerebellar ataxia will be enrolled in a double-bind, randomized,
      placebo-controlled trial.

      By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 8
      weeks.

      Electrocardiogram routine laboratory tests and pregnancy tests will be performed before drug
      administration, after 4 weeks of treatment and at the end of the study (after 8 weeks of
      treatment).

      At the same time points the International Cooperative Ataxia Rating Scale (ICARS) for
      pharmacological assessment of the cerebellar syndrome will be administered to the two groups
      (riluzole and placebo) of patients. To guarantee the evaluation of the results in blind
      conditions, the neurologists who will evaluate the ICARS scores will be different from those
      who will deal with randomisation and follow-up of patients.
    

Intervention name(s): Riluzole; placebo
Intervention type(s): Drug; Other
Intervention description(s): capsule-shaped 50 mg tablets bid for 8 weeks; capsule-shaped tablet bid for 8 weeks
Other intervention name(s): Rilutek ATC Code N07X X02
Intervention MeSH terms: Riluzole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cerebellar ataxia; deep cerebellar nuclei (DCN); small-conductance calcium-activated potassium(SK)channels; riluzole; Sporadic ataxia; Multiple system atrophy type C