Spinocerebellar Ataxia Type 2
Conditions
Keywords
Spinocerebellar ataxia-SCA2, SARA (Scale for the Assessment and Rating of Ataxia) score, Riluzole (Rilutek)
Brief summary
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. Riluzole 50 mg will be administered (per os) twice a day, versus one group with placebo for 12 months. Riluzole (Rilutek®) is a benzothiazole drug, market approved, for Amyotrophic Lateral Sclerosis (ALS). It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase survival. Scale for the Assessment and Rating of Ataxia (SARA) will be used at M0, M6 and M12. To assess primary criterion, the percentage of patients with a decrease of at least 1 point of the SARA score between the inclusion visit, and Visit 3 (Months 12) will be calculated.
Detailed description
Inherited cerebellar ataxias are genetically heterogeneous neurological disorders. They are characterized by ataxic gait and cerebellar dysarthria that progresses over time with loss of ambulation and speech. The mutations by expansions of CAG triplets in the genes ATXN1 (SCA1), ATXN 2 (SCA2), 3 (SCA3), CACNA1A (SCA6), ATXN 7 (SCA7), and TBP (SCA17) are responsible for 50% of hereditary forms There is no curative or preventive treatment. This phase III study is a multi-centric, double-blind randomized, two-arm controlled study (one group with 50 mg Riluzole twice a day versus one group with placebo), to measure the efficacy of treatment with riluzole in SCA2 patients during 12 months. Amelioration is defined by a 1 point decrease of the SARA score.
Interventions
DRUGRiluzole
50 mg will be administered (per os) twice a day
DRUGPlacebo
50 mg will be administered (per os) twice a day
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Treatments will be presented in numbered boxes, labeled for this study according to the Good Manufacturing Practices by the General Agency of Equipment and Health Products (AGEPS). Each numbered box will consist of 6 months of treatment: 20 blister packs of 20 active or placebo tablets
Intervention model description
Multi-centric, double-blind randomized, two-arm controlled study (one group with 50 mg riluzole twice a day versus one group with placebo), during one year
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Genetically diagnosed SCA2 (CAG triplet in ATXN2 ≥ 33) * At least 18 years of age * Signature of informed consent * Covered by social security * SARA score ≥ 5 and ≤ 26 * Age at onset ≤ 50 years old
Exclusion criteria
* Treated with riluzole prior to the study * Hepatotoxic medication * Hypersensitivity to the active substance or to any of the excipients * Serious systemic illnesses or conditions known for enhancing the side effects of riluzole * Contraindications for MRI examination * Participation in another therapeutic trial (3 months exclusion period) * Pregnancy or breastfeeding * Non abstinence or absence of effective contraception for women * Inability to understand information about the protocol * Persons deprived of their liberty by judicial or administrative decision * Adult subject under legal protection or unable to consent * Other ataxic syndromes than SCA2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ataxia symptoms (Scale for the Assessment and Rating of Ataxia (SARA)) | at 12 months. | To compare the proportion of patients with Scale for the Assessment and Rating of Ataxia (SARA) improvement (decrease) of at least one point from baseline to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ataxia symptoms (Composite Cerebellar Functional Severity (CCFS) score) | at 12 months | To compare the difference of the CCFS score (Composite Cerebellar Functional Severity Score) from baseline at 12 months. A decrease is expected in the intervention group. |
| Change in extracerebellar symptoms (Inventory of Non-Ataxia Signs (INAS)) | at 12 months | To compare the difference of the extracerebellar symptoms (INAS, Inventory of Non-Ataxia Signs) by showing decrease in the INAS count from baseline at 12 months |
| 12 months survival | at 12 months | To compare survival of the patients between the two treatment groups at 12 months |
Countries
France
Outcome results
None listed