A Study of Resveratrol as Treatment for Friedreich Ataxia

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of two doses of resveratrol taken for a 12 week period, on frataxin levels in individuals with Friedreich ataxia. This study will also measure the effect of resveratrol on markers of oxidative stress, clinical measures of ataxia, and cardiac parameters.

Detailed Description
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Resveratrol shows promise as an agent for the treatment of Friedreich ataxia due to its antioxidant properties, neuroprotective effects, and ability to increase frataxin levels in vitro and in vivo. This clinical pilot study aims to determine the effect of two doses of resveratrol (1g/day and 5g/day) taken for 12 weeks, on frataxin levels in individuals with Friedreich ataxia. Additional outcome measures include the effect of resveratrol on markers of oxidative stress, clinical measures of ataxia , and cardiac parameters (including relative wall thickness and left ventricular mass index).

Official Title
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An Open Label Clinical Pilot Study of Resveratrol as Treatment for Friedreich Ataxia

Conditions
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Friedreich Ataxia

Intervention / Treatment
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* Drug: Resveratrol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with Friedreich ataxia due to homozygosity for the GAA repeat expansion in intron 1 of the FXN gene Functional stage on the Ataxia subscale of the FARS of 1 or higher Exclusion Criteria: Women who are pregnant or lactating Active arrythmias or significant cardiac insufficiency Use of idebenone, Coenzyme Q or vitamin E within 30 days prior to enrolment Use of amiodarone or other medications which may have clinically significant drug interactions that cannot be safely monitored

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resveratrol, 1g daily<br>15 participants will receive resveratrol 1g daily | Drug: Resveratrol<br>* Resveratrol 1g daily (500mg twice daily) for 12 weeks Resveratrol 5 daily (2.5g twice daily) for 12 weeks<br>|
| Active Comparator: Resveratrol, 5g daily<br>15 participants will receive resveratrol, 5g daily | Drug: Resveratrol<br>* Resveratrol 1g daily (500mg twice daily) for 12 weeks Resveratrol 5 daily (2.5g twice daily) for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lymphocyte frataxin level | Change in lymphocyte frataxin levels at 12 weeks compared to baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress markers | Oxidative stress, as measured by a) plasma F2-isoprostanes and b) urinary 8-hydroxyl-2-deoxyguanosine levels at 12 weeks compared to baseline | 12 weeks | 
| Clinical rating scales of ataxia | Clinical rating scales of ataxia at 12 weeks will be compared to baseline. This will include: a) Friedreich Ataxia Rating Scale (FARS) b) International Cooperative Ataxia Rating Scale (ICARS) c) Scale for the Assessment and Rating of Ataxia (SARA) d) Friedreich Ataxia Functional Composite | 12 weeks | 
| Echocardiogram measures | Changes in structural and functional 3D echocardiogram measures from baseline to 12 weeks will be reported | 12 weeks | 
| Pharmacokinetic studies of resveratrol | Pharmacokinetic data will be collected 45, 90 and 120 minutes after the first dose of resveratrol. Plasma concentration of resveratrol and its sulfate and glucuronide metabolites will be measured in ng/mL. | First 2 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Friedreich ataxia, Resveratrol, Frataxin, Cardiomyopathy, Oxidative stress