Phase 2
N=15
Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents
Duchenne Muscular Dystrophy
Bottom Line
View on ClinicalTrials.gov: NCT02964377 ↗Enrolled (actual)
15
Serious AEs
0.0%
Results posted
Dec 2021
Primary outcome: Primary: Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) — 15.1; 33.9; 20.6; 481.2 nM — p=0.0482
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- (+)- Epicatechin (Drug)
- Age
- Pediatric · 8+ yrs
- Sex
- Male
- Sponsor
- Craig McDonald, MD
- Primary completion
- Jul 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) |
84.2; 163.8; 179.1; 742.8; 601; 5590.8 | 0.0127 sig |
| PRIMARY Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) |
84.2; 163.8; 179.1; 742.8; 601; 5590.8 | 0.0127 sig |
| PRIMARY Laboratory Outcome: Absolute Plasma Follistatin:Myostatin Ratio at Baseline, Week 4 and Week 8 |
1.82; 1.76; 3.31; 3.61; 3.41; 5.26 | <0.0001 sig |
| PRIMARY Clinical Outcome: Mean Percent of Baseline Cardiac Ejection Fraction by MRI |
98.19; 96.23; 92.27 | — |
| PRIMARY Safety: Number of Participants Who Experienced Treatment-Related Laboratory Abnormalities |
1; 0; 2 | — |
| PRIMARY Laboratory Outcome: Absolute Values of Nitric Oxide (AU) Measured by ELISA |
0.65; 0.63; 0.57; 0.82; 1.06; 0.93 | 0.002 sig |
| PRIMARY Laboratory Outcome: Absolute Values of Carbonylation (AU) Measured by ELISA |
12.85; 15.7; 12.45; 9.95; 12.2; 7.18 | <0.0001 sig |
| PRIMARY Laboratory Outcome: Absolute Values of Follistatin (AU) Measured by ELISA |
527.24; 555.71; 1011.25; 891.43; 795.71; 1356.25 | <0.0001 sig |
| PRIMARY Laboratory Outcome: Absolute Values of Myostatin (AU) Measured by ELISA |
282.33; 302.33; 316.6; 247.67; 239; 263.67 | 0.012 sig |
| SECONDARY Clinical Outcome: Percent of Normalized Upper Extremity Reachable Surface Area at Week 4 and Week 8 |
44; 89.9; 33; 63.7; 84.4; 35.8 | — |
| SECONDARY Clinical Outcome: Total Score Using Performance of the Upper Limb Assessment |
19.8; 30.8; 27; 21.4; 32; 26.8 | 0.01 sig |
| SECONDARY Clinical Outcome: Mean Maximal Attained Revolutions Per 6-minute Cycle Test |
177.4; 362.6; 330.8; 194.4; 415; 348.2 | 0.054 |
| SECONDARY Person-Reported Outcome: Upper Extremity Standardized Mean Score Using Pediatric Outcomes Data Collection Instrument (PODCI) Quality of Life Instrument |
32; 62.6; 66; 31.2; 74.6; 72.6 | 0.025 sig |
| SECONDARY Person-Reported Outcome: Mean Person-Reported Outcome Measure Upper Limb (PROM-UL) Functional Capacity Score |
73.6; 88.4; 79.2; 64; 87.4; 82.8 | 0.006 sig |
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.
Eligibility Criteria
Inclusion Criteria
- Male
- Age 8 years to 17 years
- Non-Ambulatory (unable to complete 10m run/walk under 10s)
- Weight 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.
Data sourced from ClinicalTrials.gov (NCT02964377). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.