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

Multiple Sclerosis Clinical Trial

Official title:

Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00202397
• Other study ID #: NEU - RLZ - 05
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: February 10, 2014
• Start date: June 2005
• Est. completion date: August 2008

Study information

• Verified date: December 2013
• Source: S. Andrea Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Hereditary Ataxia
• Multiple Sclerosis

Intervention

Drug:
• Riluzole
capsule-shaped 50 mg tablets bid for 8 weeks

Other:
• placebo
capsule-shaped tablet bid for 8 weeks

Locations

Country	Name	City	State
Italy	S.Andrea Hospital - University of Rome "La Sapienza"	Rome

Sponsors (1)

Lead Sponsor	Collaborator
S. Andrea Hospital

Country where clinical trial is conducted

Italy, 

References & Publications (6)

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. — View Citation

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. — View Citation

Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 1996 Dec;47(6 Suppl 4):S233-41. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No

External Links

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