Clinical Trial: Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Single Center Dose Ranging Pilot Study of (+)-Epicatechin in Non-ambulatory Adolescents With Duchenne Muscular Dystrophy and Pre-symptomatic Cardiac Dysfunction

Brief Summary: 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.

Detailed Summary:
Sponsor: Craig McDonald, MD

Current Primary Outcome:

  • Pharmacokinetics Outcome: (+)-epicatechin trough (Cmin) serum concentration [ Time Frame: Baseline, Week 2, Week 4, Week 8 ]
    Pharmacokinetic evaluation for dose-response evaluation.
  • Pharmacokinetics Outcome: (+)-epicatechin peak (Cmax) serum concentration [ Time Frame: Baseline, Week 2, Week 4, Week 8 ]
    Pharmacokinetic evaluation for dose-response evaluation.
  • Laboratory Outcome: Change in plasma follistatin:myostatin ratio [ Time Frame: Baseline, Week 4, Week 8 ]
    Evaluation of follistatin:myostatin ratio from plasma samples.
  • Clinical Outcome: Percent change in cardiac ejection fraction and shortening fraction by MRI [ Time Frame: Baseline, Week 8 ]
    Evaluation of change in cardiac volume and performance.
  • Safety: Clinical laboratory blood chemistry evaluation [ Time Frame: Screening, Baseline, Week 2, Week 4, Week 8 ]
    Evaluation of routine safety laboratory blood chemistry assessments for clinical safety monitoring.
  • Safety: Complete blood count evaluation [ Time Frame: Screening, Baseline, Week 2, Week 4, Week 8 ]
    Evaluation of routine complete blood count for clinical safety monitoring.
  • Safety: Urinalysis [ Time Frame: Screening, Baseline, Week 2, Week 4, Week 8 ]
    Evaluation of routine urinalysis for clinical safety mon

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Clinical Outcome: Percent change in normalized upper extremity reachable surface area. [ Time Frame: Baseline, Week 4, Week 8 ]
    • Clinical Outcome: Percent change in Performance of the Upper Limb Assessment score. [ Time Frame: Baseline, Week 4, Week 8 ]
    • Clinical Outcome: Percent change in 6-minute cycle test maximal attained revolutions. [ Time Frame: Baseline, Week 4, Week 8 ]
    • Person-Reported Outcome: Percent change in POSNA Pediatric Outcomes Data Collection Instrument (PODCI) quality of life instrument score [ Time Frame: Baseline, Week 4, Week 8 ]
    • Person-Reported Outcome: Percent change in Person-Reported Outcome Measure Upper Limb (PROM-UL) functional capacity score. [ Time Frame: Baseline, Week 4, Week 8 ]


    Original Secondary Outcome: Same as current

    Information By: University of California, Davis

    Dates:
    Date Received: November 7, 2016
    Date Started: November 2016
    Date Completion: May 2017
    Last Updated: November 10, 2016
    Last Verified: November 2016