Riluzole in Patients With Spinocerebellar Ataxia Type 7: a Randomized , Double-blind, Placebo-controlled Pilot Trial With a Lead in Phase
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- visual acuity expressed as log MAR units
研究概览
简要总结
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 relentless course, the important visual deficit that accompanies CA, and the possibility of disease development in childhood are pressing unmet needs. The investigators published encouraging data on riluzole in inherited CA other than SCA7. These results prompted off-label use of riluzole in single cases of SCA7 in Italy and United States, suggesting possible efficacy of the drug in this condition.
详细描述
The investigators propose a clinical trial in SCA7 patients performing a serial evaluation of riluzole effects on stringent outcome measures: ophthalmological metrics, scale for the assessment and rating of ataxia (SARA) scores, and safety biomarkers.
The study design will be a randomized , double-blind, placebo-controlled pilot trial with a lead-in phase. The design will include a run-in 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 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 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.
Participants will be randomly assigned (1:1) 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •positive genetic test for SCA7.
排除标准
- •cardiac arrhythmias;
- •haematologic diseases;
- •hepatic diseases with serum values of alanine aminotransferase, aspartate aminotransferase or bilirubin > 1·5 times above normal limit;
- •pregnancy (women of childbearing potential agreed to use contraception);
- •breastfeeding.
研究组 & 干预措施
Placebo + riluzole
Placebo twice daily for 6 months and riluzole 50 mg twice daily for the following 6 months in the comparison group
干预措施: Placebo (Drug)
Riluzole
Riluzole 50 mg twice daily for 12 months in the treated group. In pre-pubertal subjects the dosage will be adjusted on a mg/m2 basis according to the recommended human daily dose (RHDD; 100 mg).
干预措施: Riluzole (Drug)
Placebo + riluzole
Placebo twice daily for 6 months and riluzole 50 mg twice daily for the following 6 months in the comparison group
干预措施: Riluzole (Drug)
结局指标
主要结局
visual acuity expressed as log MAR units
时间窗: 18 months
the metric to quantify the best corrected visual acuity, by applying the ETDRS chart (either back-illuminated or projected) with the patient's correction for distance
the proportion of patients with stable Scale for the assessment and rating of ataxia (SARA) score
时间窗: 18 months
neurological assessment for ataxia. It has eight categories with accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia). When completing the outcome measure each category is assessed and scored accordingly. Scores for the eight items range as follows: Gait (0-8 points), Stance (0-6 points), Sitting (0-4 points) Speech disturbance (0-6 points) Finger chase (0-4 points) Nose-finger test (0-4 points) Fast alternating hand movement (0-4 points) Heel-shin slide (0-4 points) Once each of the 8 categories have been assessed, the total is calculated to determine the severity of ataxia. For motor activities of the four extremities (items 5-8), assessments are performed bilaterally, and the mean values are used to obtain the total score.
次要结局
- Scale for the assessment and rating of ataxia (SARA) score(18 months)
- Farnsworth D15 Arrangement Test(18 months)
- Visual evoked potentials(18 months)
- Optical Coherence tomography(18 months)
- Electroretinography(18 months)
研究者
Giovanni Ristori
Principal Investigator
S. Andrea Hospital