A Randomised Placebo-controlled Crossover Trial of Micronised Resveratrol as a Treatment for Friedreich Ataxia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Modified Friedreich Ataxia Rating Scale
研究概览
简要总结
The aim of this study is to assess the efficacy of micronised resveratrol as a treatment for FRDA, in terms of reducing the severity of ataxia symptoms at 24 weeks, through a randomised blinded, placebo controlled crossover trial.
详细描述
Friedreich ataxia (FRDA) is the most common hereditary ataxia, with an estimated prevalence in Caucasians of 1 in 30,000. Neurological features of FRDA are progressive gait and limb ataxia, absent lower limb reflexes, and loss of position and vibration sense. There are currently no treatments proven to alter the natural history of FRDA. Resveratrol is a naturally occurring compound found in red wine, berries, and nuts. It is postulated to have wide-ranging health benefits, including antioxidant, anticarcinogenic, antidiabetic and neuroprotective properties.
The study will be a double-blinded, placebo-controlled randomised 2-period crossover trial of 2g/day of micronised resveratrol in FRDA over 24 weeks. The study will enrol 40 patients with FRDA from 3 sites. The primary outcome measure is the change in modified Friedreich Ataxia Rating Scale (mFARS) score from baseline to 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will be randomised between receiving resveratrol in period 1 and placebo in period 2, or placebo in period 1 and resveratrol in period 2.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥16 years.
- •Diagnosis of FRDA, genetically documented to be due to homozygosity for a GAA repeat expansion in intron 1 of FXN.
- •Functional stage on the Ataxia subscale of the full FARS of 1 or higher (a score of 1 is assigned if the subject has "Minimal signs detected by the physician during screening. Can run or jump without loss of balance. No disability."), and total mFARS score of ≤
- •Adequate end organ function defined as follows: (i) total bilirubin <2x upper limit of normal unless attributable to Gilbert disease, (ii) ALT and AST <1.5x upper limit of normal, (iii) Creatinine <2x upper limit of normal, (iv) neutrophils >1.5x10^9/L, (v) platelets >10^6/μL.
- •Written informed consent provided.
排除标准
- •Non-elective hospitalisation within the past 60 days that could be of concern in the investigator's judgment. Any hospitalisation in the previous 60 days will be assessed and if in the investigator's judgement it could compromise the individual or the study, that person will not be recruited. Examples include if the individual is hospitalised for management of cardiac morbidity such as uncontrolled arrhythmia or angina or for orthopaedic surgery for a lower limb fracture.
- •Women who are pregnant or lactating or men and women of childbearing potential who are unwilling to use contraception for the duration of the study.
- •FRDA due to compound heterozygosity for an expanded GAA repeat and a point mutation/ deletion in the FXN gene.
- •Current or recent (in last 12 months) arrhythmias including: atrial fibrillation, atrial flutter, sinus tachycardia >120/min, sinus bradycardia <50/min. Symptomatic paroxysmal arrhythmia which is recurring frequently. Cardiac insufficiency (by New York Heart Association >2). Reduced LV ejection fraction (<50%) in the last six months.
- •Medical illness that in the judgment of the investigator would jeopardise the safe completion of the study. Examples include cancer, chronic inflammatory disease, severe diabetes (type I or II, HbA1c >8%), chronic liver insufficiency, epilepsy, thrombocytosis.
- •Evidence of end organ dysfunction through failure to meet one or more parameters in inclusion criterion number
- •Prior invasive cancer (excluding localised basal cell or squamous cell skin cancer).
- •Known hypersensitivity to resveratrol.
- •Use of any investigational agent within 30 days of enrolment.
- •Use of antioxidants such as vitamin E, coenzyme Q10 or idebenone within 30 days prior to enrolment.
- •Concomitant use of medications with potential for clinically relevant drug interactions. This includes medications with a narrow therapeutic range that are metabolised by the cytochrome P450 3A4, 2D6 or 2C9 systems e.g. warfarin, amiodarone.
研究组 & 干预措施
Resveratrol followed by placebo
1g micronised resveratrol twice daily for 24 weeks, a wash-out period of 4 weeks, followed by twice daily placebo for 24 weeks.
干预措施: Resveratrol (Drug)
Placebo followed by Resveratrol
Twice daily placebo for 24 weeks, a wash-out period of 4 weeks, followed by 1g micronised resveratrol twice daily for 24 weeks
干预措施: Resveratrol (Drug)
结局指标
主要结局
Modified Friedreich Ataxia Rating Scale
时间窗: 24 weeks
Change in the Modified Friedreich Ataxia Rating Scale score (score range 0-99) at 24 weeks compared with baseline. Higher scores are indicative of more severe disease.
次要结局
- Berg Balance Scale(24 weeks)
- Friedreich Ataxia Impact Scale(24 weeks)
- Modified Fatigue Impact Scale(24 weeks)
- Nine-Hole Peg Test(24 weeks)
- Ataxia Instrumented Measure-Spoon(24 weeks)
- Measures of speech(24 weeks)
- Frataxin levels(24 weeks)
- Measures of hearing(24 weeks)
- Cardiac parameters measured by echocardiography(24 weeks)
- Cardiac parameters measured by ECG(24 weeks)
- Plasma F2-isoprostane levels(24 weeks)
- mRNA levels(24 weeks)