Use of (-)-Epicatechin in the Treatment of Becker Muscular Dystrophy (Pilot Study)
- Conditions
- Becker Muscular Dystrophy
- Interventions
- Drug: (-)-epicatechin
- Registration Number
- NCT01856868
- Lead Sponsor
- Craig McDonald, MD
- Brief Summary
(-)-Epicatechin will be evaluated for the treatment of progressive muscle loss and impaired skeletal muscle function in Becker Muscular Dystrophy (BMD) patients.
- Detailed Description
This is a proof-of-concept phase 1/2a pilot and endpoint development study that is designed to provide initial evidence of biological activity of (-)-epicatechin. Primary endpoints include initial assessment of tissue-specific evidence of efficacy from muscle biopsy samples. Secondary endpoints include measures of strength and physical function, and safety and adverse event data. Pilot endpoints include assessment of mRNA and miRNA peripheral blood profiles and validation of non-invasive near-infrared spectroscopy (NIRS) muscle perfusion studies during exercise and a recumbent cycle exercise test that may be employed as endpoints in future clinical trials.
This single center open-label pilot study will enroll 10 adults with genetically-confirmed Becker muscular dystrophy, who will receive the purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. After screening visits, participants will be enrolled in the study if they meet all inclusion criteria. They will be evaluated at baseline and at screening, day 1, and weeks 1, 2, 4 and 8.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 7
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Male
-
Age 18 years to 60 years
-
Average to low daily physical activity
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Ability to ambulate for 75 meters without assistive devices
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Diagnosis of BMD confirmed by at least one the following:
- Dystrophin immunofluorescence and/or immunoblot showing partial dystrophin deficiency, and clinical picture consistent with typical BMD, or
- Gene deletions test positive (missing one or more exons) of the dystrophin gene, where reading frame can be predicted as 'in-frame', and clinical picture consistent with typical BMD, or
- Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, or other mutation resulting in a stop codon mutation) that can be definitely associated with BMD, with a typical clinical picture of BMD, or
- Positive family history of BMD confirmed by one of the criteria listed above in a sibling or maternal uncle, and clinical picture typical of BMD.
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Nutritional, herbal and antioxidant supplements taken with the intent of maintaining or improving skeletal muscle strength or functional mobility have been discontinued at least 2 weeks prior to screening (daily multivitamin use is acceptable).
-
Hematology profile within normal range
-
Baseline laboratory safety chemistry profile within normal range
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No plan to change exercise regimen during study participation
- Currently enrolled in another treatment clinical trial.
- History of significant concomitant illness or significant impairment of renal or hepatic function.
- Use of regular daily aspirin or other medication with antiplatelet effects within 3 weeks of first dose of study medication.
- Regular participation in vigorous exercise.
- Symptomatic heart failure with cardiac ejection fraction <25%
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment with Epicatechin (-)-epicatechin Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in Muscle Tissue Myogenin at 8 Weeks 8 weeks Modulators of skeletal muscle regeneration by Western will include myogenin will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue Dysferlin at 8 Weeks 8 weeks Structure associated indicators including dysferlin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Cristae-associated Mitofillin Levels at 8 Weeks 8 weeks Western blot measurement of Mitofillin will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software.
Mean Change From Baseline in Muscle Tissue Myf5 at 8 Weeks 8 weeks Modulators of skeletal muscle regeneration My5 will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue LKB1 at 8 Weeks 8 weeks Western blot measurement of LKB1 will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software) .
Mean Change From Baseline in Muscle Tissue MyoD at 8 Weeks 8 weeks Modulators of skeletal muscle regeneration MyoD will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue MEF2a at 8 Weeks 8 weeks Modulators of skeletal muscle regeneration MEF2a will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue AMPK at 8 Weeks 8 weeks Western blot measurement of AMPK will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue Follistatin at 8 Weeks 8 weeks Regulators of muscle growth and regeneration including follistatin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue Utrophin at 8 Weeks 8 weeks Structure associated indicators including utrophin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Mean Change From Baseline in Muscle Tissue Myostatin at 8 Weeks 8 weeks Regulators of muscle growth and regeneration including myostatin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Change From Baseline in Muscle Tissue PGC1alpha (AU) at 8 Weeks Baseline and 8 Weeks Western blot measurement of the transcriptional coactivator gene PGC1alpha involved in mitochondrial biogenesis will be assessed using relative band intensities of the pre-treatment (Baseline) and post-treatment (8 Weeks) specimens with digitally quantified using ImageJ software.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Stand From Supine at 8 Weeks Baseline and 8 Weeks Muscle burst function will be assessed by time function tests.
-(-)Epicatechin Pharmacokinetics 8 Weeks Pharmacokinetics sequentially after dosing will be measured.
Change From Baseline in Knee Extension at 8 Weeks Baseline and 8 Weeks Knee extension will be assessed using an isokinetic dynamometer.
Participants With Abnormal Treatment-Related Laboratory Assessments 8 weeks Standard safety monitoring of plasma hematologic, hepatologic, renal and metabolic parameters will be assessed. Abnormal will be defined as values outside of typical range for patients with Becker Muscular Dystrophy.
Change From Baseline in 6-Minute Walk Distance at 8 Weeks Baseline and 8 Weeks Muscle function will be assessed by measuring the 6-minute walk distance
Change From Baseline in Elbow Flexion at 8 Weeks Baseline and 8 Weeks Elbow flexion will be assessed using an isokinetic dynamometer.
Trial Locations
- Locations (1)
University of California, Davis
🇺🇸Sacramento, California, United States
University of California, Davis🇺🇸Sacramento, California, United States