This is a Phase 1, open-label, dose escalation study aimed at evaluating the safety, early efficacy and potential biomarkers of (+)-epicatechin in patients with Becker or Becker-like Muscular Dystrophy (BMD).
The safety and tolerability of three escalating doses of (+)-epicatechin will be assessed and early effectiveness measured by changes in plasma biomarkers, tissue biomarkers from muscle biopsies, cardiac imaging, and on clinical function assessments of participants' muscle strength. All patients will receive oral (+)-epicatechin for a total duration of approximately 52 weeks. Three doses of (+)-epicatechin will be tested in sequential 2 month periods with total daily doses of 75, 150, and 225 mg/day (+)-epicatechin. Doses will be escalated every 2 months, if tolerated, for the first 6 months of the study. Participants will then continue to receive the highest does they tolerated for an additional 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
(+)-Epicatechin is a synthetic flavanol
UCLA Dept of Human Genetics
Los Angeles, California, United States
University of California - Davis Department of Physical Medicine and Rehabilitation
Sacramento, California, United States
Washington University School of Medicine
St Louis, Missouri, United States
Number of participants with treatment-emergent adverse events (TEAEs)
The TEAEs will be graded using the adult National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: Through study completion, up to 1 year
Change in cardiac function as assessed by cardiac magnetic resonance imaging (MRI)
Time frame: Through study completion, up to 1 year
Change in cardiac function as assessed by plasma biomarkers [e.g. pro-B-type natriuretic peptide (pro-BNP), nitrates].
Time frame: Through study completion, up to 1 year
Change in muscle function as assessed by 6-minute walk test (6MWT)
Time frame: Through study completion, up to 1 year
Change in muscle function as assessed by Time to Run/Walk 10-meter Test (TTRW10)
Time frame: Through study completion, up to 1 year
Change in muscle function as assessed by Time to 4-stair Climb Test (TT4SC)
Time frame: Through study completion, up to 1 year
Change in muscle function as assessed by Time to Run/Walk 100-meter Test (TTRW100)
Time frame: Through study completion, up to 1 year
Change in muscle structure and function as assessed by Western blot analysis of biopsy specimens (e.g. dystrophin expression)
Time frame: Through study completion, up to 1 year
Change in muscle biomarkers of regeneration in biopsy specimens (e.g. follistatin)
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Time frame: Through study completion, up to 1 year
Change in plasma biomarkers of muscle regeneration (e.g. follistatin, myostatin)
Time frame: Through study completion, up to 1 year