Duchenne Muscular DystrophyPhase 1/2NCT02964377
Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents
A Phase 1/2 study testing (+)- Epicatechin in people with Duchenne Muscular Dystrophy, run by Craig McDonald, MD at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 8 to 17 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- (+)- Epicatechin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Jul 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male
- Age 8 years to 17 years
- Non-Ambulatory (unable to complete 10m run/walk under 10s)
- Weight </=100Kg
- 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
Show all 16Show fewer
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis Medical Center
Sacramento, California, 95817
About this study
Official title: 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.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- (+)- Epicatechin
- Keywords
- Pediatric, muscle disease, Duchenne muscular dystrophy, cardiomyopathy
- Medical subject headings
- Muscular Dystrophy, Duchenne, Muscular Diseases, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
(+)- EpicatechinDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 8-weeks open-label (+)- Epicatechin at 25mg/day twice per day, Receives: Drug: (+)- Epicatechin |
| Cohort 2 | Experimental | 8-weeks open-label (+)- Epicatechin at 25mg/day three times per day Receives: Drug: (+)- Epicatechin |
| Cohort 3 | Experimental | 8-weeks open-label (+)- Epicatechin at 75mg/day at two times per day Receives: Drug: (+)- Epicatechin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak)
Pharmacokinetic evaluation for dose-response evaluation.
Measured: 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)
Pharmacokinetic evaluation for dose-response evaluation.
Measured: Week 4
Laboratory Outcome: Absolute Plasma Follistatin:Myostatin Ratio at Baseline, Week 4 and Week 8
Evaluation of follistatin:myostatin ratio from plasma samples.
Measured: Baseline, Week 4 and Week 8
Clinical Outcome: Mean Percent of Baseline Cardiac Ejection Fraction by MRI
Evaluation of change in cardiac volume and performance, as measured by the mean percent of baseline ejection fraction using Cardiac MRI, measured at 8 weeks.
Measured: Week 8
Safety: Number of Participants Who Experienced Treatment-Related Laboratory Abnormalities
Treatment-related laboratory abnormalities, defined as values outside of the typical range for Duchenne Muscular Dystrophy. Safety laboratory tests included blood chemistry panel, complete blood count w/ differential panel, \& urinalysis assessments for clinical safety monitoring.
Measured: Study duration (8 weeks)
Laboratory Outcome: Absolute Values of Nitric Oxide (AU) Measured by ELISA
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline, Week 4, Week 8
Laboratory Outcome: Absolute Values of Carbonylation (AU) Measured by ELISA
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline, Week 4, Week 8
Laboratory Outcome: Absolute Values of Follistatin (AU) Measured by ELISA
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline, Week 4, Week 8
Laboratory Outcome: Absolute Values of Myostatin (AU) Measured by ELISA
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline, Week 4, Week 8
Secondary outcomes (5)
Clinical Outcome: Percent of Normalized Upper Extremity Reachable Surface Area at Week 4 and Week 8
Quantitative upper extremity reachable workspace will be assessed using the XBox Kinect system. The KINECT Upper Extremity Reachable Workspace test measures surface area of a reachable workspace "bubble", normalized to the size of the individual, noted as the RSA or Reachable Surface Area. The Total RSA measure is the sum of four quadrants dividing superior and inferior medial and lateral spaces. A total score of 1 indicates a typical reachable workspace, while lower scores indicate restrictions in one or more of the four quadrants.
Measured: Baseline, Week 4, Week 8
Clinical Outcome: Total Score Using Performance of the Upper Limb Assessment
The standardized Performance of Upper Limb (PUL) measure will be assessed at baseline and after 4 \& 8 weeks.
The Performance of the Upper Limb module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the three subscales (10 upper, 10 mid, and 14 distal).
Measured: Baseline, Week 4, Week 8
Clinical Outcome: Mean Maximal Attained Revolutions Per 6-minute Cycle Test
The Assisted Six-Minute Cycle Test is an ergometer-based assessment of upper limb function. Test results indicate the maximum number of ergometer revolutions achieved in six-minutes, with higher numbers indicating a greater degree of functional capacity.
Measured: Baseline, Week 4, Week 8
Person-Reported Outcome: Upper Extremity Standardized Mean Score Using Pediatric Outcomes Data Collection Instrument (PODCI) Quality of Life Instrument
The PODCI instrument was developed by Daltroy and colleagues with support by the Pediatric Orthopaedic Society of North America (POSNA). The PODCI is a 108-item questionnaire that evaluates global functioning in the pediatric orthopedic population utilizing four components: upper extremity functioning, transfers and basic mobility, sports and physical functioning and a comfort/pain score. Global functioning is assessed by the average of the four previous scores. All scales are scored from zero to 100, with 100 representing the highest level of functioning and least pain. The PODCI asks questions such as "During the last week, was it easy or hard for you to … lift heavy books".
Measured: Baseline to Week 4 and Week 8
Person-Reported Outcome: Mean Person-Reported Outcome Measure Upper Limb (PROM-UL) Functional Capacity Score
The Performance of Upper Limb module (PUL) for DMD was designed according to a specific contextual framework of upper limb function in both ambulant and non-ambulant individuals with DMD. The UL-PROM closely linked to this motor performance based clinician-reported outcome measure, was developed to evaluate manual ability related to activities of daily living (ADL) that cannot be observed in a clinical setting. Items were selected in relation to the different domains of the PUL from proximal to distal performance in order to cover the full range of upper limb functions. The questionnaire consists of 33 items covering four domains (3 points each for Food/Nutrition 7 items, Self Care 8 items, Household/Environment 6 items, Leisure/Communication 12 items). Higher scores indicate greater function, with total score being a sum of the subscale scores (Ranging from 0 to 99).
Measured: Change from Baseline to Week 4 and Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionJul 2018
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Craig McDonald, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Cardero Therapeutics, Inc.
- Responsible party
- Sponsor-investigator, Craig McDonald, MD, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02964377
- Sponsor's protocol ID
- 951753
- Status last verified
- Nov 2021
- First submitted
- 7 Nov 2016
- Last updated
- 21 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center Dose Ranging Pilot Study of (+)-Epicatechin in Non-ambulatory Adolescents With Duchenne Muscular Dystrophy and Pre-symptomatic Cardiac Dysfunction
- ClinicalTrials.gov ID
- NCT02964377
- Acronym / sponsor ID
- 951753
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Pediatric, muscle disease, Duchenne muscular dystrophy, cardiomyopathy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Craig McDonald, MDUniversity, hospital or other
- Collaborators
- Cardero Therapeutics, Inc.
- Study start
- Nov 2016 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 16 Nov 2016 (estimated)
- Results
- Posted 21 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: (+)- Epicatechin8-weeks open-label (+)- Epicatechin at 25mg/day twice per day, |
| Cohort 2 | Experimental | Drug: (+)- Epicatechin8-weeks open-label (+)- Epicatechin at 25mg/day three times per day |
| Cohort 3 | Experimental | Drug: (+)- Epicatechin8-weeks open-label (+)- Epicatechin at 75mg/day at two times per day |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (16 listed)
- Male
- Age 8 years to 17 years
- Non-Ambulatory (unable to complete 10m run/walk under 10s)
- Weight </=100Kg
- Diagnosis of DMD confirmed by at least one the following:
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| (+)- Epicatechin | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak)
Time frame: Pre-dose and 2 hours post-dose at baseline
Pharmacokinetic evaluation for dose-response evaluation.
Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak)
Time frame: Week 4
Pharmacokinetic evaluation for dose-response evaluation.
Laboratory Outcome: Absolute Plasma Follistatin:Myostatin Ratio at Baseline, Week 4 and Week 8
Time frame: Baseline, Week 4 and Week 8
Evaluation of follistatin:myostatin ratio from plasma samples.
Clinical Outcome: Mean Percent of Baseline Cardiac Ejection Fraction by MRI
Time frame: Week 8
Evaluation of change in cardiac volume and performance, as measured by the mean percent of baseline ejection fraction using Cardiac MRI, measured at 8 weeks.
Safety: Number of Participants Who Experienced Treatment-Related Laboratory Abnormalities
Time frame: Study duration (8 weeks)
Treatment-related laboratory abnormalities, defined as values outside of the typical range for Duchenne Muscular Dystrophy. Safety laboratory tests included blood chemistry panel, complete blood count w/ differential panel, \& urinalysis assessments for clinical safety monitoring.
Laboratory Outcome: Absolute Values of Nitric Oxide (AU) Measured by ELISA
Time frame: Baseline, Week 4, Week 8
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Laboratory Outcome: Absolute Values of Carbonylation (AU) Measured by ELISA
Time frame: Baseline, Week 4, Week 8
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Laboratory Outcome: Absolute Values of Follistatin (AU) Measured by ELISA
Time frame: Baseline, Week 4, Week 8
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
Laboratory Outcome: Absolute Values of Myostatin (AU) Measured by ELISA
Time frame: Baseline, Week 4, Week 8
Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA).
5 secondary outcomes
Clinical Outcome: Percent of Normalized Upper Extremity Reachable Surface Area at Week 4 and Week 8
Time frame: Baseline, Week 4, Week 8
Clinical Outcome: Total Score Using Performance of the Upper Limb Assessment
Time frame: Baseline, Week 4, Week 8
Clinical Outcome: Mean Maximal Attained Revolutions Per 6-minute Cycle Test
Time frame: Baseline, Week 4, Week 8
Person-Reported Outcome: Upper Extremity Standardized Mean Score Using Pediatric Outcomes Data Collection Instrument (PODCI) Quality of Life Instrument
Time frame: Baseline to Week 4 and Week 8
Person-Reported Outcome: Mean Person-Reported Outcome Measure Upper Limb (PROM-UL) Functional Capacity Score
Time frame: Change from Baseline to Week 4 and Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing (+)- Epicatechin in people with Duchenne Muscular Dystrophy, run by Craig McDonald, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) (time frame: Pre-dose and 2 hours post-dose at baseline). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2021.