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

NCT00202397 | Completed Phase 2 DMC

• 1 other identifier: NEU - RLZ - 05
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hereditary Ataxia; Multiple Sclerosis; Cerebellar Ataxia

Keywords

cerebellar ataxia; deep cerebellar nuclei (DCN); small-conductance calcium-activated potassium(SK)channels; riluzole; Sporadic ataxia; Multiple system atrophy type C

Outcome Measures

Primary Outcomes (1)

• 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

  pre-treatment, after 4 weeks of treatment and at the end of the study

Study Arms (2)

2

PLACEBO COMPARATOR

placebo bid for 8 weeks

Other: placebo

1

EXPERIMENTAL

Riluzole, capsule-shaped 50 mg tablets bid for 8 weeks

Drug: Riluzole

Interventions

Riluzole DRUG

capsule-shaped 50 mg tablets bid for 8 weeks

Also known as: Rilutek ATC Code N07X X02

1

placebo OTHER

capsule-shaped tablet bid for 8 weeks

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• S. Andrea Hospital: lead

Study Sites (1)

S.Andrea Hospital - University of Rome "La Sapienza"

Rome, 00100, Italy

Location

Related Publications (6)

• Shakkottai VG, Chou CH, Oddo S, Sailer CA, Knaus HG, Gutman GA, Barish ME, LaFerla FM, Chandy KG. Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia. J Clin Invest. 2004 Feb;113(4):582-90. doi: 10.1172/JCI20216.

  PMID: 14966567 BACKGROUND

• Aizenman CD, Huang EJ, Linden DJ. Morphological correlates of intrinsic electrical excitability in neurons of the deep cerebellar nuclei. J Neurophysiol. 2003 Apr;89(4):1738-47. doi: 10.1152/jn.01043.2002.

  PMID: 12686564 BACKGROUND

• Raman IM, Gustafson AE, Padgett D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci. 2000 Dec 15;20(24):9004-16. doi: 10.1523/JNEUROSCI.20-24-09004.2000.

  PMID: 11124976 BACKGROUND

• Cao YJ, Dreixler JC, Couey JJ, Houamed KM. Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur J Pharmacol. 2002 Aug 2;449(1-2):47-54. doi: 10.1016/s0014-2999(02)01987-8.

  PMID: 12163105 BACKGROUND

• Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 1996 Dec;47(6 Suppl 4):S233-41. doi: 10.1212/wnl.47.6_suppl_4.233s.

  PMID: 8959995 BACKGROUND

• Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci. 1997 Feb 12;145(2):205-11. doi: 10.1016/s0022-510x(96)00231-6.

  PMID: 9094050 BACKGROUND

Related Links

• sponsor site

MeSH Terms

Conditions

Spinocerebellar Degenerations; Multiple Sclerosis; Cerebellar Ataxia

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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

• Marco Salvetti, Assoc. Prof

  S.Andrea Hospital, University of Rome "La Sapienza"

  STUDY DIRECTOR

• Giovanni Ristori, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: June 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: August 1, 2008
• Last Updated: December 2, 2024

Record last verified: 2024-11

Locations

IT (1)