Translating Molecular Pathology Into a Therapeutic Strategy in SCA38, a Newly Identified Form of Spinocerebellar Ataxia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Change from Baseline SARA score at 16 weeks and 40 weeks
研究概览
简要总结
The project will study a therapeutic approach in Spinocerebellar Ataxia (SCA38) by DHA replacement. SCA38 is caused by missense mutations in the ELOVL5 (Elongation of very long chain fatty acids protein 5) gene.
Background/Rationale: ELOVL5 is a microsomal fatty acid elongase gene required for the synthesis of arachidonic acid and DHA. In brain, it shows a peculiar high expression in cerebellar Purkinje cells.
The ELOVL5 products, such as DHA, are decreased in SCA38 patients serum and DHA administered as a dietary supplement has been shown to improve SARA scores, to ameliorate quality of life, and to increase brain cerebellar hypometabolism (FDG-PET) in two SCA38 patients.
Experimental Plan: The investigators will perform a randomized placebo-controlled trial by DHA supplementation on ten SCA38 patients, followed by an open-label phase.
Expected results: DHA supplementation should be able to improve symptoms in SCA38 and to improve cerebellar hypometabolism in these patients.
详细描述
Spinocerebellar ataxias (SCAs) include over thirty different subtypes of central nervous system diseases that affect approximately 1 in 30,000 persons. The investigators have identified the causative gene for SCA38, a novel rare form of cerebellar ataxia. Estimated frequency of the disease is below 1% of SCAs. The disease gene encodes an enzyme involved in omega-3 fatty acid biosynthesis, whose products are reduced in SCA38 patients' serum.
The investigators reasoned that the administration of specific omega-3 fatty acids could ameliorate the disease symptoms in SCA38 patients. Indeed, preliminary data obtained in a pilot trial on two patients, now in their 8th-month therapy, are remarkable, with an improvement of disease symptoms and quality of life, without any adverse effect.
The investigators will perform a clinical trial to prove this therapeutic strategy of SCA38. The investigators will evaluate clinical SARA scores, ICARS scores, brain PET images, and plasma metabolic pattern in ten SCA38 patients.
The trial will consist of two phases: 1) a randomized double-blind placebo/treatment (600 mg DHA/day) from T0 (baseline observation) to T1 (evaluation at four-month). Patients who will meet the study eligibility criteria will be randomized to receive the drug or the placebo (ratio 1:1). A second open-label phase on all patients from T2 (6 months) to T5 (30 months) will be performed with repeated measures of the medication group (n=10).
Patients will complete a personal diary during the whole treatment and a quality of life questionnaire at each visit. The primary outcome will be the clinical improvement, whilst secondary outcome will be considered the improvement of brain metabolism by PET-FDG.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mutations p.Gly230Val in ELOVL5 gene
- •Clinical symptoms of ataxia
排除标准
- •Use of fish oil or DHA dietary supplement within 30 days prior the enrollment in the present trial
- •Evidence of poorly controlled diabetes (defined as hemoglobin A1c > 8% in patients with diabetes)
- •Average alcohol consumption of more than one drink or equivalent (>12 g) per day or more than two drinks on any 1 day over the 30 days prior to screening.
- •Serum creatinine level 2.0 mg/dL or greater or currently on dialysis
- •Evidence of drug abuse within 6 months prior to entering the study or during the screening period
- •Reported poor compliance to drug assumption
- •Bedridden patients (SARA score >23)
研究组 & 干预措施
placebo administration
placebo will be made with the same colour and taste, in softgel as DHA, and will be administered for 16 weeks to 5 patients in double blind.
干预措施: DHA (Dietary Supplement)
DHA administration
DHA 600 mg/day will be administered for 16 weeks to 5 patients in double blind
干预措施: DHA (Dietary Supplement)
结局指标
主要结局
Change from Baseline SARA score at 16 weeks and 40 weeks
时间窗: baseline, 16 weeks, 40 weeks
improvement of ataxia by SARA scores
Change from Baseline ICARS score at 16 weeks and 40 weeks
时间窗: baseline, 16 weeks, 40 weeks
improvement of ataxia by ICARS scores
次要结局
- Brain FDG-PET(baseline, 16 weeks, 40 weeks)
研究者
Barbara Borroni
Associated Professor of Neurology, MD
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia