Efficacy of Riluzole in Hereditary Cerebellar Ataxia

Cerebellar Ataxia Clinical Trial

Official title:

Efficacy of Riluzole in Hereditary Cerebellar Ataxia: a Randomized Double-blind Placebo-controlled Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01104649
• Other study ID #: FARM7KAJM7
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 7, 2010
• Last updated: April 20, 2015
• Start date: April 2010
• Est. completion date: March 2014

Study information

• Verified date: April 2015
• Source: S. Andrea Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients with genetically confirmed diagnosis of hereditary cerebellar ataxia

Exclusion Criteria:

• Concomitant experimental therapy for ataxia

• Serious systemic illnesses

• Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Spinocerebellar Degenerations

Intervention

Drug:
• riluzole
Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
• Placebo comparator
Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Locations

Country	Name	City	State
Italy	Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome	Rome

Sponsors (2)

Lead Sponsor	Collaborator
S. Andrea Hospital	Agenzia Italiana del Farmaco

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Ristori G, Romano S, Visconti A, Cannoni S, Spadaro M, Frontali M, Pontieri FE, Vanacore N, Salvetti M. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010 Mar 9;74(10):839-45. doi: 10.1212/WNL.0b013e3181d31e23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Scale for the assessment and rating of ataxia (SARA)	Improvement in ataxia	12 months	No
Secondary	Baropodometric parameters		12 months	No
Secondary	Quality of life	SF-36	12 months	No
Secondary	Depression	Beck Scale	12 months	No