Resveratrol Supplementation in Patients With Mitochondrial Myopathies and Skeletal Muscle Fatty Acid Oxidation Disorders

Resveratrol Supplementation in Patients With Mitochondrial Myopathies and Skeletal Muscle Fatty Acid Oxidation Disorders: A Double-blind, Placebo-controlled, Cross Over Study

The purpose of this study is to investigate the potential beneficial effects of a daily supplement of Resveratrol (1000mg/day) on physical ability and on muscle metabolism in patients with verified mitochondrial myopathy and patients with a verified fatty acid oxidation defect of VLCAD and CPTII deficiencies. Investigators hypothesize an improved muscle metabolism, mitochondrial function, fatty acid oxidation and thus improvement of physical ability.

Study Overview

• Status: Completed
• Conditions: Mitochondrial Myopathies; Fatty Acid Oxidation Defects
• Intervention / Treatment: Dietary supplement: Resveratrol

Detailed Description

Study design: double-blind, randomized, placebo-controlled, cross-over study.

To ensure enough participants, and due to the risk of a heterogeneous cohort, a cross-over design is chosen, where participants are their own controls. 10 patients with mitochondrial myopathy and 10 patients with fatty acid oxidation defects will be included. Eligible patients will be randomized using a 1:1 assignment ratio to receive placebo or RSV first. Each treatment will be administered orally twice daily for 8 weeks, followed by a 4 weeks wash-out, and afterwards a new 8-week treatment period.

During the 20-week trial period, subjects will visit the trial site on five occasions, for functional assessments (cycle ergometer testing), blood sampling and questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen Neuromuscular Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is willing and able to provide written informed consent prior to participation.
2. Patient is ≥18 and ≤80 years of age at baseline.
3. Patients have genetically verified mitochondrial disorder or a fatty acid oxidation deficiency (VLCAD/CPTII).
4. Patient has a clinical presentation, signs or symptoms suggestive of myopathy (e.g., easy fatigability, exercise intolerance, muscle pain) in the opinion of the Investigator.
5. Patient is ambulatory.

Exclusion Criteria:

1. Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements.
2. Patient has symptoms of mitochondrial myopathy due to known secondary mitochondrial dysfunction (e.g., drug-induced myopathy).
3. Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments.
4. Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Resveratrol; Resveratrol supplementation 1000 mg /day or placebo
Experimental: Resveratrol; Over the counter supplement	Dietary supplement: Resveratrol; Resveratrol supplementation 1000 mg /day or placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Decrease in heart rate during constant load cycling exercise.	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen utilization	VO^2max (ml/min)	20 weeks
Fatty acid oxidation	Fatty acid oxidation will be assessed by stable isotope technique (only for fatty acid oxidation defect disease subgroup)	20 weeks
Perceived exertion	Evaluation of perceived exertion (Borg score) during constant workload cycling	20 weeks
Fatigue Severity Scale score	Evaluation of self-rated fatigue	20 weeks
SF-36 questionnaire	Evaluation of self-rated daily function scores	20 weeks

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: John Vissing, professor, Copenhangen Neuromuscular Center, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: November 1, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Mitochondrial Diseases; Muscular Diseases; Mitochondrial Myopathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: H-17039503

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No