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

Phase 2

Completed

Brief 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
2	placebo	placebo bid for 8 weeks
1	Riluzole	Riluzole, capsule-shaped 50 mg tablets bid for 8 weeks

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method

Locations (1): S.Andrea Hospital - University of Rome "La Sapienza"
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Rome, Italy

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