Clinical trial NCT03347344: Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)
Official title: Multicenter, Randomized, Double Blind, Placebo Controlled Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinocerebellar Ataxia Type 2
Keywords: Spinocerebellar ataxia-SCA2
SARA (Scale for the Assessment and Rating of Ataxia) score
Riluzole (Rilutek)
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-11-20
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Ataxia symptoms (Scale for the Assessment and Rating of Ataxia (SARA))
timeFrame: at 12 months.
Secondary outcomes:
measure: Change in Ataxia symptoms (Composite Cerebellar Functional Severity (CCFS) score)
timeFrame: at 12 months
measure: Change in extracerebellar symptoms (Inventory of Non-Ataxia Signs (INAS))
timeFrame: at 12 months
measure: 12 months survival
timeFrame: at 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Durr
Study officials:
affiliation: ASSISTANCE PUBLIQUE HÖPITAUX DE PARIS
name: DURR Alexandra, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coarelli G, Heinzmann A, Ewenczyk C, Fischer C, Chupin M, Monin ML, Hurmic H, Calvas F, Calvas P, Goizet C, Thobois S, Anheim M, Nguyen K, Devos D, Verny C, Ricigliano VAG, Mangin JF, Brice A, Tezenas du Montcel S, Durr A. Safety and efficacy of riluzole in spinocerebellar ataxia type 2 in France (ATRIL): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2022 Mar;21(3):225-233. doi: 10.1016/S1474-4422(21)00457-9. Epub 2022 Jan 18.