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Trial record 5 of 86 for:    Recruiting, Not yet recruiting, Available Studies | "Muscular Dystrophies"

Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents

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ClinicalTrials.gov Identifier: NCT02964377
Recruitment Status : Recruiting
First Posted : November 16, 2016
Last Update Posted : November 16, 2016
Sponsor:
Collaborator:
Cardero Therapeutics, Inc.
Information provided by (Responsible Party):
Craig McDonald, MD, University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: (+)- Epicatechin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Center Dose Ranging Pilot Study of (+)-Epicatechin in Non-ambulatory Adolescents With Duchenne Muscular Dystrophy and Pre-symptomatic Cardiac Dysfunction
Study Start Date : November 2016
Estimated Primary Completion Date : April 2017
Estimated Study Completion Date : May 2017


Arm Intervention/treatment
Experimental: Open-label (+)- Epicatechin
8-weeks open-label (+)- Epicatechin at 25mg/day twice per day, 25mg/day three times per day, or 50mg/day at three times per day.
Drug: (+)- Epicatechin



Primary Outcome Measures :
  1. Pharmacokinetics Outcome: (+)-epicatechin trough (Cmin) serum concentration [ Time Frame: Baseline, Week 2, Week 4, Week 8 ]
    Pharmacokinetic evaluation for dose-response evaluation.

  2. Pharmacokinetics Outcome: (+)-epicatechin peak (Cmax) serum concentration [ Time Frame: Baseline, Week 2, Week 4, Week 8 ]
    Pharmacokinetic evaluation for dose-response evaluation.

  3. Laboratory Outcome: Change in plasma follistatin:myostatin ratio [ Time Frame: Baseline, Week 4, Week 8 ]
    Evaluation of follistatin:myostatin ratio from plasma samples.

  4. 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.

  5. 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.

  6. 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.

  7. Safety: Urinalysis [ Time Frame: Screening, Baseline, Week 2, Week 4, Week 8 ]
    Evaluation of routine urinalysis for clinical safety monitoring.


Secondary Outcome Measures :
  1. Clinical Outcome: Percent change in normalized upper extremity reachable surface area. [ Time Frame: Baseline, Week 4, Week 8 ]
  2. Clinical Outcome: Percent change in Performance of the Upper Limb Assessment score. [ Time Frame: Baseline, Week 4, Week 8 ]
  3. Clinical Outcome: Percent change in 6-minute cycle test maximal attained revolutions. [ Time Frame: Baseline, Week 4, Week 8 ]
  4. 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 ]
  5. Person-Reported Outcome: Percent change in Person-Reported Outcome Measure Upper Limb (PROM-UL) functional capacity score. [ Time Frame: Baseline, Week 4, Week 8 ]

Other Outcome Measures:
  1. 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.

  2. 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.

  3. Clinical Outcome: Percent change in cardiac circumferential strain by MRI [ Time Frame: Baseline, Week 8 ]
    Cardiac lateral and posterior wall strain by cardiac MRI



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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964377


Contacts
Contact: Alina Nicorici, BS 916-734-0968 arnicorici@ucdavis.edu

Locations
United States, California
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Alina Nicorici, BS    916-734-0968    arnicorici@ucdavis.edu   
Principal Investigator: Craig M McDonald, MD         
Sub-Investigator: Erik K Henricson, PhD, MPH         
Sponsors and Collaborators
Craig McDonald, MD
Cardero Therapeutics, Inc.

Responsible Party: Craig McDonald, MD, Professor and Chair of Department of Physical Rehabilitation, University of California, Davis
ClinicalTrials.gov Identifier: NCT02964377     History of Changes
Other Study ID Numbers: 951753
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: November 16, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Craig McDonald, MD, University of California, Davis:
Pediatric
muscle disease
Duchenne muscular dystrophy
cardiomyopathy

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked