Riluzole in Patients With Spinocerebellar Ataxia Type 7

The investigators propose a clinical trial?clinical trial A study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects. in SCA7 patients performing a serial evaluation of riluzole effects on stringent outcome measures?outcome measures Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.: ophthalmological metrics, scale for the assessment and rating of ataxia (SARA) scores, and safety biomarkers?biomarkers Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.. The study design will be a randomized?randomized Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable. , double-blind?double-blind Two types of people involved in the study do not know which intervention a participant is receiving. The ClinicalTrials.gov record specifies who is masked, for example participants, care providers, investigators or outcome assessors., placebo-controlled?placebo-controlled A study design in which one group receives a placebo so that the study treatment's effects can be compared with no active treatment. pilot trial with a lead-in phase. The design will include a run-in?run-in A period at the start of a study, before the study treatment begins, used for example to confirm that participants meet the criteria or to record their usual symptoms. phase of 6 months for all the participants, assessing ophthalmological metrics and SARA scores at the month 0, 3, and 6. Then one arm will undergo riluzole for other 12 months, while the other will take placebo?placebo A treatment that looks like the study treatment but contains no active ingredient. Some participants receive it instead of the study treatment, usually without knowing which they got. for 6 months, and riluzole for the following 6 months; from both groups the same evaluations will be obtained at the month 12, 15 and 18 of the study. Thirty-four patients will be enrolled at 4 clinical Centers (3 in Italy and one in U.S.). The clinical epidemiology aspects (design of the study, statistical analysis and enrollment?enrollment The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined. process) will be followed by National Rare Diseases Centre and Complex Diseases Group of National Centre of Epidemiology, Surveillance and Health Promotion of National Institute of Health. Eligible subjects for this study are patients (at least 7-year old) with positive genetic test for SCA7. Serious systemic illnesses or conditions (cardiac, haematologic and hepatic diseases) known for enhancing the side effects of riluzole, pregnancy or breastfeeding will be exclusion criteria?exclusion criteria The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.. Participants will be randomly assigned (1:1?1:1 How many participants go to each group. In a 2:1 ratio, two are assigned to the first group for every one assigned to the second.) to riluzole (50 mg twice daily) or placebo. In pre-pubertal subjects the dosage will be adjusted on a mg/m2 basis according to the recommended human daily dose (100 mg). At baseline?baseline Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them. and after 3, 6, 12, 15 and 18 months, symptoms, physical and neurological signs, and SARA score will be recorded. At the same time points the following quantitative ophthalmologic assessments will be performed:

• corrected visual acuity (right eye and left eye measurements) expressed as logMAR units with the ETDRS chart (either back-illuminated or projected).
• Color vision via a Farnsworth D15 Arrangement Test.
• Visual evoked potential are elicited using transient Pattern Reversal stimuli and monocular stimulation.
• Electroretinography
• Optical Coherence tomography with macular map of both eyes.
• Computerized visual field examination by standard automated perimetry and kinetic perimetry Every three months electrocardiogram?electrocardiogram A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged. and a laboratory profile will be obtained for drug safety.

The co-primary endpoints will be the proportion of patients with stability of SARA score and visual acuity (in log MAR units) at 18 months, compared to the mean values of t0-t3-t6 evaluations. A sample size of 17 patients per group (a total of 34 patients) had 80% power and an α value of 10% to detect a difference between the two groups of 35% in the co-primary end points. This calculation took into account published data on riluzole in CA. Data will be expressed as mean (SD) for continuous variables and as proportions for categorical variables. Comparisons between riluzole and placebo group will be assessed using the t test for unpaired data for continuous variables and odds ratio with a relative 95% CI for categorical data. An intention-to-treat analysis will be done adopting a last observation carried forward method. A logistic regression model will be done at 18 months to adjust the results for the main baseline characteristics; p values less than 0.05 will be considered significant.