Micronised Resveratrol as a Treatment for Friedreich Ataxia

NCT ID: NCT03933163

Last Updated: 2024-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-23
• Study Completion Date: 2024-03-28

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.

Conditions

Friedreich Ataxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: OTHER

Resveratrol

Intervention Type: DRUG

Drug name: Micronised resveratrol. Dosage form: 500mg capsules. Alternate name: 1,3-Benzenediol, 5-\[2-(4-hydroxyphenyl)ethenyl\]-, (E). Ingredients: 99.50% pure trans-resveratrol. Placebo capsules will be identical in terms of taste, smell, and appearance.

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

Group Type: OTHER

Resveratrol

Intervention Type: DRUG

Drug name: Micronised resveratrol. Dosage form: 500mg capsules. Alternate name: 1,3-Benzenediol, 5-\[2-(4-hydroxyphenyl)ethenyl\]-, (E). Ingredients: 99.50% pure trans-resveratrol. Placebo capsules will be identical in terms of taste, smell, and appearance.

Interventions

Resveratrol

Drug name: Micronised resveratrol. Dosage form: 500mg capsules. Alternate name: 1,3-Benzenediol, 5-\[2-(4-hydroxyphenyl)ethenyl\]-, (E). Ingredients: 99.50% pure trans-resveratrol. Placebo capsules will be identical in terms of taste, smell, and appearance.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Murdoch Childrens Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin B Delatycki, PhD, MBBS

Role: PRINCIPAL_INVESTIGATOR

Murdoch Childrens Research Institute

Locations

Royal North Shore Hospital

St Leonards, New South Wales, Australia

University of Queensland Centre for Clinical Research

Herston, Queensland, Australia

Murdoch Children's Research Institute

Parkville, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Countries

Australia

Other Identifiers

36007

Identifier Type: -

Identifier Source: org_study_id