Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT03347344

Collaborator

(none)

Enrollment

Location

Arms

34.9

Actual Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinocerebellar Ataxia Type 2	Drug: Riluzole Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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 yearMulti-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

Masking:

Triple (Participant, Care Provider, 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

Primary Purpose:

Treatment

Official Title:

Multicenter, Randomized, Double Blind, Placebo Controlled Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2

Actual Study Start Date :

Jan 17, 2018

Actual Primary Completion Date :

Dec 14, 2020

Actual Study Completion Date :

Dec 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RILUZOLE Riluzole PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet. The tablets will be held under a blister of 20 tablets.	Drug: Riluzole 50 mg will be administered (per os) twice a day
Placebo Comparator: PLACEBO The placebo PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet matching the appearance of the Riluzole used in this study	Drug: Placebo 50 mg will be administered (per os) twice a day

Arm

Intervention/Treatment

Experimental: RILUZOLE

Riluzole PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet. The tablets will be held under a blister of 20 tablets.

Drug: Riluzole

50 mg will be administered (per os) twice a day

Placebo Comparator: PLACEBO

The placebo PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet matching the appearance of the Riluzole used in this study

Drug: Placebo

50 mg will be administered (per os) twice a day

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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