This single center open-label pilot study will enroll 15 non-ambulatory children with Duchenne muscular dystrophy at least 8 years of age and who demonstrate pre-clinical cardiomyopathy (defined as a cardiac ejection fraction \>55% with abnormal LV strain by cardiac MRI). They will receive (+)-epicatechin at one of three doses during an 8-week dose-ranging study with assessments at baseline, 2 Weeks, 4weeks, and 8 weeks. The study will determine optimal dosing for future cardiac efficacy studies based on serum / plasma biomarker response using follistatin: myostatin ratio, nitrite/nitrate ratio, cardiac troponins and cardiac BNP. Secondary endpoints will include additional biomarker assessments by SOMAscanTM, cardiac functional evaluations by cardiac MRI (LV strain), and echocardiogram (LV strain by speckle tracking) and measures of strength, range of motion and mobility, and clinical safety assessments. Results of secondary endpoint analysis will be used to refine design of subsequent clinical trials powered to detect changes in clinical outcomes.
Age range
8 Years – 17 Years
Sex
MALE
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Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak)
Timeframe: Pre-dose and 2 hours post-dose at baseline
Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak)
Timeframe: Week 4
Laboratory Outcome: Absolute Plasma Follistatin:Myostatin Ratio at Baseline, Week 4 and Week 8
Timeframe: Baseline, Week 4 and Week 8
Clinical Outcome: Mean Percent of Baseline Cardiac Ejection Fraction by MRI
Timeframe: Week 8
Safety: Number of Participants Who Experienced Treatment-Related Laboratory Abnormalities
Timeframe: Study duration (8 weeks)
Laboratory Outcome: Absolute Values of Nitric Oxide (AU) Measured by ELISA
Timeframe: Baseline, Week 4, Week 8
Laboratory Outcome: Absolute Values of Carbonylation (AU) Measured by ELISA
Timeframe: Baseline, Week 4, Week 8
Laboratory Outcome: Absolute Values of Follistatin (AU) Measured by ELISA
Timeframe: Baseline, Week 4, Week 8
Laboratory Outcome: Absolute Values of Myostatin (AU) Measured by ELISA
Timeframe: Baseline, Week 4, Week 8