A Study of Resveratrol as Treatment for Friedreich Ataxia

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

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.

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: Resveratrol

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Melbourne, Victoria, Australia, 3168
      • Monash Medical Centre, Southern Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Collaborators: Friedreich's Ataxia Research Alliance
• Investigators: Principal Investigator: Martin Delatycki, MBBS PhD, Murdoch Childrens Research Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 14, 2011
• First Submitted That Met QC Criteria: April 20, 2011
• First Posted (Estimate): April 21, 2011

Study Record Updates

• Last Update Posted (Estimate): January 22, 2014
• Last Update Submitted That Met QC Criteria: January 19, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Oxidative stress; Cardiomyopathy; Resveratrol; Friedreich ataxia; Frataxin
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: 10358B