Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Orthopedic |
| Therapuetic Areas: | Neurology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 8 - 17 |
| Updated: | 1/19/2019 |
| Start Date: | November 2016 |
| End Date: | July 2018 |
A Single Center Dose Ranging Pilot Study of (+)-Epicatechin in Non-ambulatory Adolescents With Duchenne Muscular Dystrophy and Pre-symptomatic Cardiac Dysfunction
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.
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.
Inclusion Criteria:
- Male
- Age 8 years to 17 years
- Non-Ambulatory (unable to complete 10m run/walk under 10s)
- Weight
- Diagnosis of DMD confirmed by at least one the following:
- Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin
deficiency, and clinical picture consistent with typical DMD, or
- Gene deletions test positive (missing one or more exons) of the dystrophin gene,
where reading frame can be predicted as 'out-of-frame', and clinical picture
consistent with typical DMD, 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 DMD, with a typical clinical picture of DMD, or
- Positive family history of DMD confirmed by one of the criteria listed above in a
sibling or maternal uncle, and clinical picture typical of DMD.
- Cardiac ejection fraction >55% on echocardiogram
- Use of nutritional, herbal and antioxidant supplements taken with the intent of
maintaining or improving skeletal muscle strength or functional mobility has been
discontinued at least 4 weeks prior to screening (daily multivitamin use is
acceptable).
- Glucocorticoid therapy, if used, must have a stable weight-based dose for at least 3
months prior to enrollment
- Cardiac therapy, if used, includes prophylactic ACE inhibitors, aldosterone receptor
antagonists (e.g.
spironolactone, eplerenone, etc.), and/or beta-blocker therapy, and must be stable for 3
months prior to enrollment.
- Hematology profile within normal range.
- Baseline laboratory safety chemistry profile within typical range for DMD (elevated
ALT / AST acceptable in the absence of elevated GGT, elevated CK acceptable).
Exclusion Criteria:
- Inability to complete cardiac or strength, range of motion and mobility assessments
per protocol
- Current enrollment 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.
- Cardiac symptoms that, in the opinion of the investigator, may be suggestive of
imminent moderate to severe cardiac events, irrespective of LVEF.
We found this trial at
1
site
Sacramento, California 95814
Principal Investigator: Craig M McDonald, MD
Phone: 916-734-0968
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