Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia

This study has been completed.
Sponsor:
Information provided by:
S. Andrea Hospital
ClinicalTrials.gov Identifier:
NCT00202397
First received: September 12, 2005
Last updated: February 10, 2014
Last verified: December 2013
  Purpose

Cerebellar disorders are often disabling and symptomatic therapies are limited to few options that are partially effective. It seems therefore appropriate to search for additional approaches.

Purkinje cells are the sole output of the cerebellar cortex: they 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. Recent evidences support the notion that an increase in DCN excitability may be an important step in the development of cerebellar ataxia and point to the underlying molecular mechanisms: the inhibition of small-conductance calcium-activated potassium (SK) channels, that causes an increase of the firing frequency in DCN, correlates with cerebellar ataxia.

The rationale of the present project is that SK channel openers, such as riluzole, may have a beneficial effect on cerebellar ataxia.

The researchers propose to perform a pilot study investigating safety and efficacy of riluzole, an approved treatment for amyotrophic lateral sclerosis, as a symptomatic approach in patients with chronic cerebellar ataxia.


Condition Intervention Phase
Hereditary Ataxia
Multiple Sclerosis
Cerebellar Ataxia
Drug: Riluzole
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia

Resource links provided by NLM:


Further study details as provided by S. Andrea Hospital:

Primary Outcome Measures:
  • The International Cooperative Ataxia Rating Scale (ICARS) total scores and subscores (oculomotor, kinetic, postural, speech), comparing the three time points in the treated versus placebo group [ Time Frame: pre-treatment, after 4 weeks of treatment and at the end of the study ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: June 2005
Study Completion Date: August 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
placebo bid for 8 weeks
Other: placebo
capsule-shaped tablet bid for 8 weeks
Experimental: 1
Riluzole, capsule-shaped 50 mg tablets bid for 8 weeks
Drug: Riluzole
capsule-shaped 50 mg tablets bid for 8 weeks
Other Name: Rilutek ATC Code N07X X02

Detailed Description:

Forty patients with chronic cerebellar ataxia will be enrolled in a double-bind, randomized, placebo-controlled trial.

By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 8 weeks.

Electrocardiogram routine laboratory tests and pregnancy tests will be performed before drug administration, after 4 weeks of treatment and at the end of the study (after 8 weeks of treatment).

At the same time points the International Cooperative Ataxia Rating Scale (ICARS) for pharmacological assessment of the cerebellar syndrome will be administered to the two groups (riluzole and placebo) of patients. To guarantee the evaluation of the results in blind conditions, the neurologists who will evaluate the ICARS scores will be different from those who will deal with randomisation and follow-up of patients.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with cerebellar degeneration (heredoataxias, sporadic idiopathic ataxia, multiple system atrophy type C)
  • Patients who meet McDonald criteria for probable or definite multiple sclerosis (MS) with chronic cerebellar ataxia (not acute cerebellar ataxia due to relapse)
  • Age between 18 and 80 years

Exclusion Criteria:

  • Ataxia due to other diseases
  • Acute cerebellar ataxia
  • Use of other drugs for chronic ataxia
  • Serious concomitant illnesses (cardiac arrhythmias, haematological and hepatic diseases)
  • Pregnancy or breast feeding
  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: NCT00202397

Locations
Italy
S.Andrea Hospital - University of Rome "La Sapienza"
Rome, Italy, 00100
Sponsors and Collaborators
S. Andrea Hospital
Investigators
Study Director: Marco Salvetti, Assoc. Prof S.Andrea Hospital, University of Rome "La Sapienza"
Principal Investigator: Giovanni Ristori, MD University of Roma La Sapienza
  More Information

Additional Information:
Publications:
Responsible Party: Giovanni Ristori, S.Andrea Hospital - II Faculty of Medicine, "Sapienza" University of Rome
ClinicalTrials.gov Identifier: NCT00202397     History of Changes
Other Study ID Numbers: NEU - RLZ - 05
Study First Received: September 12, 2005
Last Updated: February 10, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by S. Andrea Hospital:
cerebellar ataxia
deep cerebellar nuclei (DCN)
small-conductance calcium-activated potassium(SK)channels
riluzole
Sporadic ataxia
Multiple system atrophy type C

Additional relevant MeSH terms:
Ataxia
Cerebellar Ataxia
Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Dyskinesias
Neurologic Manifestations
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Riluzole
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2014