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

• ClinicalTrials.gov Identifier: NCT03728777
• Recruitment Status: Completed
• First Posted: November 2, 2018
• Last Update Posted: November 27, 2019
• Sponsor: Rigshospitalet, Denmark
• Information provided by (Responsible Party): Nicoline Løkken, Rigshospitalet, Denmark

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Mitochondrial Myopathies; Fatty Acid Oxidation Defects	Dietary Supplement: Resveratrol	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: double-blind, randomized, placebo-controlled, cross-over study.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Resveratrol Supplementation in Patients With Mitochondrial Myopathies and Skeletal Muscle Fatty Acid Oxidation Disorders: A Double-blind, Placebo-controlled, Cross Over Study
• Actual Study Start Date: April 9, 2018
• Actual Primary Completion Date: October 1, 2019
• Actual Study Completion Date: October 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Heart rate [ Time Frame: 20 weeks ]
   Decrease in heart rate during constant load cycling exercise.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Denmark

Copenhagen Neuromuscular Center

Copenhagen, Denmark, 2100

Sponsors and Collaborators

Rigshospitalet, Denmark

Investigators

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

More Information

• Responsible Party: Nicoline Løkken, Medical Doctor, Rigshospitalet, Denmark
• ClinicalTrials.gov Identifier: NCT03728777
• Other Study ID Numbers: H-17039503
• First Posted: November 2, 2018
• Last Update Posted: November 27, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Diseases; Mitochondrial Myopathies; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Mitochondrial Diseases; Metabolic Diseases; Resveratrol; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Enzyme Inhibitors; Platelet Aggregation Inhibitors