The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03933163




Registration number
NCT03933163
Ethics application status
Date submitted
16/04/2019
Date registered
1/05/2019
Date last updated
14/08/2019

Titles & IDs
Public title
Micronised Resveratrol as a Treatment for Friedreich Ataxia
Scientific title
A Randomised Placebo-controlled Crossover Trial of Micronised Resveratrol as a Treatment for Friedreich Ataxia
Secondary ID [1] 0 0
36007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Friedreich Ataxia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Resveratrol

Other: 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.

Other: 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


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Nine-Hole Peg Test - Change in the Nine-Hole Peg Test at 24 weeks compared with baseline.
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
Berg Balance Scale - Change in the Berg Balance Scale (score range 0-56) at 24 weeks compared with baseline. A higher score indicates lower fall risk.
Timepoint [2] 0 0
24 weeks
Secondary outcome [3] 0 0
Ataxia Instrumented Measure-Spoon - Change in the Ataxia Instrumented Measure-Spoon at 24 weeks compared with baseline.
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
Friedreich Ataxia Impact Scale - Change in the Friedreich Ataxia Impact Scale at 24 weeks compared with baseline. The Friedreich Ataxia Impact Scale comprises 8 subscales (score range 0-100) that are scored independently. A higher score indicates greater impact of Friedreich ataxia on health and well-being.
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
Modified Fatigue Impact Scale - Change in the Modified Fatigue Impact Scale (score range 0-24) at 24 weeks compared with baseline. Higher scores indicate a greater impact of fatigue on an individual's activities.
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
Measures of speech - Change in measures of speech (reading a paragraph, produce a prolonged vowel sound for 5 seconds, count from one to 20, and produce a 1-minute monologue on a pre-specified topic) at 24 weeks compared with baseline.
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Measures of hearing - Change in measures of hearing using the Listening in Spatialized Noise Test (LiSN-S) at 24 weeks compared with baseline.
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
Cardiac parameters measured by echocardiography - Change in left ventricular global longitudinal strain at 24 weeks compared to baseline.
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
Cardiac parameters measured by ECG - Change in QRS duration at lead V5 at 24 weeks compared to baseline.
Timepoint [9] 0 0
24 weeks
Secondary outcome [10] 0 0
Frataxin levels - Change in frataxin levels at 24 weeks compared to baseline.
Timepoint [10] 0 0
24 weeks
Secondary outcome [11] 0 0
mRNA levels - Change in PGC-1a mRNA levels and Nrf2 mRNA levels at 24 weeks compared to baseline.
Timepoint [11] 0 0
24 weeks
Secondary outcome [12] 0 0
Plasma F2-isoprostane levels - Change in plasma F2-isoprostane levels at 24 weeks compared to baseline.
Timepoint [12] 0 0
24 weeks

Eligibility
Key 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.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
University of Queensland Centre for Clinical Research - Herston
Recruitment hospital [2] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
6000 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03933163
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martin B Delatycki, PhD, MBBS
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Geneieve Tai
Address 0 0
Country 0 0
Phone 0 0
+61 3 8341 6374
Fax 0 0
Email 0 0
geneieve.tai@mcri.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03933163