Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia

Conditions
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Hereditary Ataxia, Multiple Sclerosis, Cerebellar Ataxia

Intervention / Treatment
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* Drug: Riluzole
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cerebellar degeneration (heredoataxias, sporadic idiopathic ataxia, multiple system atrophy type C) Patients who meet McDonald criteria for probable or definite multiple sclerosis (MS) with chronic cerebellar ataxia (not acute cerebellar ataxia due to relapse) Age between 18 and 80 years Exclusion Criteria: Ataxia due to other diseases Acute cerebellar ataxia Use of other drugs for chronic ataxia Serious concomitant illnesses (cardiac arrhythmias, haematological and hepatic diseases) Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 2<br>placebo bid for 8 weeks | Other: placebo<br>* capsule-shaped tablet bid for 8 weeks<br>|
| Experimental: 1<br>Riluzole, capsule-shaped 50 mg tablets bid for 8 weeks | Drug: Riluzole<br>* capsule-shaped 50 mg tablets bid for 8 weeks<br>* Other names: Rilutek ATC Code N07X X02;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The International Cooperative Ataxia Rating Scale (ICARS) total scores and subscores (oculomotor, kinetic, postural, speech), comparing the three time points in the treated versus placebo group |  | pre-treatment, after 4 weeks of treatment and at the end of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebellar ataxia, deep cerebellar nuclei (DCN), small-conductance calcium-activated potassium(SK)channels, riluzole, Sporadic ataxia, Multiple system atrophy type C