Clinical trial NCT03933163: Micronised Resveratrol as a Treatment for Friedreich Ataxia
Official title: A Randomised Placebo-controlled Crossover Trial of Micronised Resveratrol as a Treatment for Friedreich Ataxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Friedreich Ataxia
Keywords: Resveratrol
Frataxin
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2019-05-01
Enrollment: 25
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, randomised, placebo-controlled 2-period crossover trial of 2g/day of micronised resveratrol versus placebo. Participants will be randomised in terms of the order in which they received micronised resveratrol and placebo.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥16 years.
2. Diagnosis of FRDA, genetically documented to be due to homozygosity for a GAA repeat expansion in intron 1 of FXN.
3. 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 ≤ 65.
4. 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.
5. Written informed consent provided.

Exclusion Criteria:

1. 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.
2. 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.
3. FRDA due to compound heterozygosity for an expanded GAA repeat and a point mutation/ deletion in the FXN gene.
4. 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.
5. 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.
6. Evidence of end organ dysfunction through failure to meet one or more parameters in inclusion criterion number 4.
7. Prior invasive cancer (excluding localised basal cell or squamous cell skin cancer).
8. Known hypersensitivity to resveratrol.
9. Use of any investigational agent within 30 days of enrolment.
10. Use of antioxidants such as vitamin E, coenzyme Q10 or idebenone within 30 days prior to enrolment.
11. 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.

Primary outcomes:
measure: Modified Friedreich Ataxia Rating Scale
timeFrame: 24 weeks
Secondary outcomes:
measure: Nine-Hole Peg Test
timeFrame: 24 weeks
measure: Berg Balance Scale
timeFrame: 24 weeks
measure: Ataxia Instrumented Measure-Spoon
timeFrame: 24 weeks
measure: Friedreich Ataxia Impact Scale
timeFrame: 24 weeks
measure: Modified Fatigue Impact Scale
timeFrame: 24 weeks
measure: Measures of speech
timeFrame: 24 weeks
measure: Measures of hearing
timeFrame: 24 weeks
measure: Cardiac parameters measured by echocardiography
timeFrame: 24 weeks
measure: Cardiac parameters measured by ECG
timeFrame: 24 weeks
measure: Frataxin levels
timeFrame: 24 weeks
measure: mRNA levels
timeFrame: 24 weeks
measure: Plasma F2-isoprostane levels
timeFrame: 24 weeks
Other outcomes:
Locations:
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Herston
country: Australia
facility: University of Queensland Centre for Clinical Research
state: Queensland
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Martin B Delatycki, PhD, MBBS
role: PRINCIPAL_INVESTIGATOR
References: