Efficacy of Riluzole in Hereditary Cerebellar Ataxia

NCT01104649 | Completed Phase 2 DMC

• 1 other identifier: FARM7KAJM7
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cerebellar Ataxia

Keywords

Spinocerebellar ataxia; Friedreich ataxia

Outcome Measures

Primary Outcomes (1)

• Scale for the assessment and rating of ataxia (SARA)

  Improvement in ataxia

  12 months

Secondary Outcomes (3)

• Baropodometric parameters

  12 months

• Quality of life

  12 months

• Depression

  12 months

Study Arms (2)

Riluzole

EXPERIMENTAL

Riluzole 50 mg is administered orally every 12 hours for 12 months (a 2:1 ratio for SCA/FA in the stratified randomization procedure)

Drug: riluzole

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)

Drug: Placebo comparator

Interventions

riluzole DRUG

Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Also known as: Rilutek

Riluzole

Placebo comparator DRUG

Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.

Also known as: Placebo

Placebo comparator

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with genetically confirmed diagnosis of hereditary cerebellar ataxia

You may not qualify if:

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

Sponsors & Collaborators

• S. Andrea Hospital: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

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

Rome, 00139, Italy

Location

Related Publications (2)

• 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.

  PMID: 20211908 BACKGROUND

• Romano S, Coarelli G, Marcotulli C, Leonardi L, Piccolo F, Spadaro M, Frontali M, Ferraldeschi M, Vulpiani MC, Ponzelli F, Salvetti M, Orzi F, Petrucci A, Vanacore N, Casali C, Ristori G. Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015 Oct;14(10):985-91. doi: 10.1016/S1474-4422(15)00201-X. Epub 2015 Aug 25.

  PMID: 26321318 DERIVED

MeSH Terms

Conditions

Cerebellar Ataxia; Spinocerebellar Ataxias; Friedreich Ataxia

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Silvia Romano, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 7, 2010
• First Posted: April 15, 2010
• Study Start: April 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 21, 2015

Record last verified: 2015-04

Locations

IT (1)