Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 30 of 1005 for:    BMD

Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02964377
Recruitment Status : Completed
First Posted : November 16, 2016
Last Update Posted : January 17, 2019
Sponsor:
Collaborator:
Cardero Therapeutics, Inc.
Information provided by (Responsible Party):
Craig McDonald, MD, University of California, Davis

Tracking Information
First Submitted Date  ICMJE November 7, 2016
First Posted Date  ICMJE November 16, 2016
Last Update Posted Date January 17, 2019
Actual Study Start Date  ICMJE November 2016
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • 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: Change from Baseline to Week 4 and 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: Change from Baseline to Week 4 and 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 monitoring.
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2016)
  • 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 monitoring.
Change History Complete list of historical versions of study NCT02964377 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • Clinical Outcome: Percent change in normalized upper extremity reachable surface area. [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    Quantitative upper extremity reachable workspace will be assess using the XBox Kinect system.
  • Clinical Outcome: Percent change in Performance of the Upper Limb Assessment score. [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    The standardized Performance of Upper Limb (PUL) measure will be assessed at baseline and after 8 weeks.
  • Clinical Outcome: Percent change in 6-minute cycle test maximal attained revolutions. [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    The upper extremity 6-minute cycle test (work output and revolutions per 6-minutes) will be assessed as a measure of endurance.
  • Person-Reported Outcome: Percent change in POSNA Pediatric Outcomes Data Collection Instrument (PODCI) quality of life instrument score [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    The Total, Transfer / basic Mobility, and upper limb health-related Quality of Life will be assed using the PODCI / POSNA
  • Person-Reported Outcome: Percent change in Person-Reported Outcome Measure Upper Limb (PROM-UL) functional capacity score. [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    Upper limb self-reported function will be assessed using the Person-Reported Outcome Measure Upper Limb (PROM-UL) functional capacity score.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2016)
  • 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 ]
Current Other Pre-specified Outcome Measures
 (submitted: June 6, 2018)
  • Laboratory Outcome: Expression fold change in plasma biomarker panel by SomaSCAN [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    Proteomics evaluation of 1400 circulating biomarkers to identify intervention-responsive biological / pathophysiological pathways.
  • Laboratory Outcome: Expression fold change in plasma biomarker panel by ELISA. [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways.
  • Clinical Outcome: Percent change in cardiac circumferential strain by MRI [ Time Frame: Change from Baseline to Week 4 and Week 8 ]
    Cardiac lateral and posterior wall strain by cardiac MRI
Original Other Pre-specified Outcome Measures
 (submitted: November 10, 2016)
  • Laboratory Outcome: Expression fold change in plasma biomarker panel by SomaSCAN [ Time Frame: Baseline, Week 4, Week 8 ]
    Proteomics evaluation of 1400 circulating biomarkers to identify intervention-responsive biological / pathophysiological pathways.
  • Laboratory Outcome: Expression fold change in plasma biomarker panel by ELISA. [ Time Frame: Baseline, Week 4, Week 8 ]
    Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways.
  • Clinical Outcome: Percent change in cardiac circumferential strain by MRI [ Time Frame: Baseline, Week 8 ]
    Cardiac lateral and posterior wall strain by cardiac MRI
 
Descriptive Information
Brief Title  ICMJE Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE Drug: (+)- Epicatechin
Study Arms  ICMJE Experimental: Open-label (+)- Epicatechin
8-weeks open-label (+)- Epicatechin at 25mg/day twice per day, 25mg/day three times per day, or 75mg/day at two times per day.
Intervention: Drug: (+)- Epicatechin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 10, 2016)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2018
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 8 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02964377
Other Study ID Numbers  ICMJE 951753
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Craig McDonald, MD, University of California, Davis
Study Sponsor  ICMJE Craig McDonald, MD
Collaborators  ICMJE Cardero Therapeutics, Inc.
Investigators  ICMJE Not Provided
PRS Account University of California, Davis
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP