Efficacy of Riluzole in Hereditary Cerebellar Ataxia

April 20, 2015 updated by: Giovanni Ristori, S. Andrea Hospital

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

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.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Rome, Italy, 00139
        • Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with genetically confirmed diagnosis of hereditary cerebellar ataxia

Exclusion Criteria:

  • Concomitant experimental therapy for ataxia
  • Serious systemic illnesses
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Riluzole
Riluzole 50 mg is administered orally every 12 hours for 12 months (a 2:1 ratio for SCA/FA in the stratified randomization procedure)
Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other Names:
  • Rilutek
Placebo Comparator: Placebo comparator
Placebo is administered orally every 12 hours for 12 months (a 2:1 ratio for SCA/FA in the stratified randomization procedure)
Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Scale for the assessment and rating of ataxia (SARA)
Time Frame: 12 months
Improvement in ataxia
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baropodometric parameters
Time Frame: 12 months
12 months
Quality of life
Time Frame: 12 months
SF-36
12 months
Depression
Time Frame: 12 months
Beck Scale
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Silvia Romano, MD, PhD, Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

April 7, 2010

First Submitted That Met QC Criteria

April 14, 2010

First Posted (Estimate)

April 15, 2010

Study Record Updates

Last Update Posted (Estimate)

April 21, 2015

Last Update Submitted That Met QC Criteria

April 20, 2015

Last Verified

April 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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