Micronised Resveratrol as a Treatment for Friedreich Ataxia

NCT03933163 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 36007
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

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.

Conditions

Friedreich Ataxia

Keywords

Resveratrol; Frataxin

Outcome Measures

Primary Outcomes (1)

• Modified Friedreich Ataxia Rating Scale

  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.

  24 weeks

Secondary Outcomes (12)

• Nine-Hole Peg Test

  24 weeks

• Berg Balance Scale

  24 weeks

• Ataxia Instrumented Measure-Spoon

  24 weeks

• Friedreich Ataxia Impact Scale

  24 weeks

• Modified Fatigue Impact Scale

  24 weeks

Study Arms (2)

Resveratrol followed by placebo

OTHER

1g micronised resveratrol twice daily for 24 weeks, a wash-out period of 4 weeks, followed by twice daily placebo for 24 weeks.

Drug: Resveratrol

Placebo followed by Resveratrol

OTHER

Twice daily placebo for 24 weeks, a wash-out period of 4 weeks, followed by 1g micronised resveratrol twice daily for 24 weeks

Drug: Resveratrol

Interventions

Resveratrol 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; Resveratrol followed by placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤ 65.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (4)

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

University of Queensland Centre for Clinical Research

Herston, Queensland, 4029, Australia

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Study Officials

• Martin B Delatycki, PhD, MBBS

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: May 1, 2019
• Study Start: May 23, 2019
• Primary Completion: March 28, 2024
• Study Completion: March 28, 2024
• Last Updated: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after publication of primary outcome
• Access Criteria: Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties and there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.

Locations

AU (4)