Efficacy of Riluzole in Hereditary Cerebellar Ataxia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by S. Andrea Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
S. Andrea Hospital
ClinicalTrials.gov Identifier:
NCT01104649
First received: April 7, 2010
Last updated: July 19, 2011
Last verified: July 2011
  Purpose

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 ICARS and Scale for the Assessment and Rating of Ataxia (SARA) before treatment and during therapy at months 3, 6, 9 ,12.


Condition Intervention Phase
Cerebellar Ataxia
Drug: riluzole
Other: Placebo comparator
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Riluzole in Hereditary Cerebellar Ataxia: a Randomized Double-blind Placebo-controlled Trial.

Resource links provided by NLM:


Further study details as provided by S. Andrea Hospital:

Primary Outcome Measures:
  • Scale for the assessment and rating of ataxia (SARA) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Improvement in ataxia


Secondary Outcome Measures:
  • Baropodometric parameters [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    SF-36

  • Anxiety [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    State Trait Anxiety Inventory

  • Depression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Beck Scale


Estimated Enrollment: 60
Study Start Date: April 2010
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Riluzole Drug: riluzole
Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other Name: Rilutek
Placebo Comparator: placebo Other: Placebo comparator
Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical or genetic diagnosis of hereditary cerebellar ataxia

Exclusion Criteria:

  • Concomitant experimental therapy for ataxia
  • Serious systemic illnesses
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104649

Contacts
Contact: Ristori Giovanni, MD +390633776044 giovanni.ristori@uniroma1.it

Locations
Italy
Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome Recruiting
Rome, Italy, 00139
Contact: Giovanni Ristori, MD    +390633776044    giovanni.ristori@uniroma1.it   
Contact: Silvia Romano, MD, PhD    +390633776044    silvia.romano@uniroma1.it   
Sponsors and Collaborators
S. Andrea Hospital
Investigators
Principal Investigator: Silvia Romano, MD, PhD Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome
  More Information

Additional Information:
Publications:
Responsible Party: Ristori Giovanni, Center for Experimental Neurological Therapies (CENTERS)
ClinicalTrials.gov Identifier: NCT01104649     History of Changes
Other Study ID Numbers: FARM7KAJM7
Study First Received: April 7, 2010
Last Updated: July 19, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by S. Andrea Hospital:
Spinocerebellar ataxia
Friedreich ataxia

Additional relevant MeSH terms:
Ataxia
Cerebellar Ataxia
Spinocerebellar Degenerations
Brain Diseases
Central Nervous System Diseases
Cerebellar Diseases
Dyskinesias
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Signs and Symptoms
Spinal Cord Diseases
Riluzole
Anticonvulsants
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014