Efficacy of Riluzole in Hereditary Cerebellar Ataxia
Summary
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.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Conditions
Cerebellar Ataxia
Intervention
riluzole, Placebo comparator
Location
Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, II Faculty of Medicine, "Sapienza" University of R
Rome
Italy
00139
Status
Recruiting
Source
S. Andrea Hospital
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01104649
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:14:33-0400
Clinical Trials
Riluzole in Patients With Spinocerebellar Ataxia Type 7
Spinocerebellar ataxia type 7 (SCA7) belongs to the dominant forms of inherited cerebellar ataxias (CA), being one of the rarest form. SCA7 has no therapeutic options, so that the relentle...
Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)
ATRIL is a multi-centric, double-blind randomized, two-arm controlled study. 42 SpinoCerebellar Ataxia type 2 (SCA2) patients, both gender, at least 18 years of age will be included. ...
Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia
Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is ...
Virtual Reality-based Training in Cerebellar Ataxia
The purpose of this study was to investigate the effects of virtual reality-base training for cerebellar ataxia.
Effects of Deep Brain Stimulation of the Dentate Nucleus on Cerebellar Ataxia
Cerebellar ataxias are a group of disorders caused by cerebellar affections, for which currently no specific treatment is available. Some limited studies verified the effects of cerebellar...
PubMed Articles
The Etiologies of Chronic Progressive Cerebellar Ataxia in a Korean Population.
The etiologies and frequencies of cerebellar ataxias vary between countries. Our primary aim was to determine the frequency of each diagnostic group of cerebellar ataxia patients in a Korean populatio...
Visuospatial Organization and Recall in Cerebellar Ataxia.
Poor visuospatial skills can disrupt activities of daily living. The cerebellum has been implicated in visuospatial processing, and patients with cerebellar injury often exhibit poor visuospatial skil...
Increased excitability of motor neurons in patients with amyotrophic lateral sclerosis may be a relevant factor leading to motor neuron damage. This randomized, double-blind, 3-way cross-over, placebo...
Cerebellar Ataxia in Children: A Clinical and MRI Approach to the Differential Diagnosis.
: The cerebellum has long been recognized as a fundamental structure in motor coordination. Structural cerebellar abnormalities and diseases involving the cerebellum are relatively common in children....
Dominant SCN2A Mutation Causes Familial Episodic Ataxia and Impairment of Speech Development.
Mutations in are associated with a heterogeneous clinical spectrum including epilepsy and autism. Here, we have identified a peculiar phenotype associated with vaccination related exacerbations of at...
Medical and Biotech [MESH] Definitions
Cerebellar Ataxia
Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)
Cerebellar Diseases
Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, GAIT ATAXIA, and MUSCLE HYPOTONIA.
Cerebellar Neoplasms
Primary or metastatic neoplasms of the CEREBELLUM. Tumors in this location frequently present with ATAXIA or signs of INTRACRANIAL HYPERTENSION due to obstruction of the fourth ventricle. Common primary cerebellar tumors include fibrillary ASTROCYTOMA and cerebellar HEMANGIOBLASTOMA. The cerebellum is a relatively common site for tumor metastases from the lung, breast, and other distant organs. (From Okazaki & Scheithauer, Atlas of Neuropathology, 1988, p86 and p141)
Ataxia
Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.
Paraneoplastic Cerebellar Degeneration
Cerebellar degeneration associated with a remote neoplasm. Clinical manifestations include progressive limb and GAIT ATAXIA; DYSARTHRIA; and NYSTAGMUS, PATHOLOGIC. The histologic type of the associated neoplasm is usually carcinoma or lymphoma. Pathologically the cerebellar cortex and subcortical nuclei demonstrate diffuse degenerative changes. Anti-Purkinje cell antibodies (anti-Yo) are found in the serum of approximately 50% of affected individuals. (Adams et al., Principles of Neurology, 6th ed, p686)
