- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01104649
Efficacy of Riluzole in Hereditary Cerebellar Ataxia
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
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Rome, Italy, 00139
- Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of Rome
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
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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)
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Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other Names:
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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)
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Study drug will be orally dispensed in doses of 50 mg twice daily for 12 months.
Other Names:
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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
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Improvement in ataxia
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12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Baropodometric parameters
Time Frame: 12 months
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12 months
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Quality of life
Time Frame: 12 months
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SF-36
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12 months
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Depression
Time Frame: 12 months
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Beck Scale
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12 months
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Collaborators and Investigators
Sponsor
Collaborators
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
General Publications
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Dyskinesias
- Cerebellar Diseases
- Ataxia
- Cerebellar Ataxia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Neuroprotective Agents
- Protective Agents
- Anticonvulsants
- Riluzole
Other Study ID Numbers
- FARM7KAJM7
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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