Efficacy of Riluzole in Hereditary Cerebellar Ataxia
Status:
Completed
Trial end date:
2014-03-01
Target enrollment:
Participant gender:
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.