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Use of (-)-Epicatechin in the Treatment of Becker Muscular Dystrophy (Pilot Study)

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ClinicalTrials.gov Identifier: NCT01856868
Recruitment Status : Recruiting
First Posted : May 17, 2013
Last Update Posted : June 8, 2018
Sponsor:
Collaborator:
Cardero Therapeutics, Inc.
Information provided by (Responsible Party):
Craig McDonald, MD, University of California, Davis

May 9, 2013
May 17, 2013
June 8, 2018
May 2013
October 2018   (Final data collection date for primary outcome measure)
  • Muscle tissue PGC1alpha [ Time Frame: 8 weeks ]
    Western blot measurement of the transcriptional coactivator gene PGC1alpha involved in mitochondrial biogenesis will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software)
  • Muscle tissue AMPK [ Time Frame: 8 weeks ]
    Western blot measurement of AMPK will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue LKB1 [ Time Frame: 8 weeks ]
    Western blot measurement of LKB1 will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software) .
  • Cristae-associated Mitofilin levels [ Time Frame: 8 weeks ]
    Western blot measurement of Mitofillin will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue Follistatin [ Time Frame: 8 weeks ]
    Regulators of muscle growth and regeneration including follistatin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue Myostatin [ Time Frame: 8 weeks ]
    Regulators of muscle growth and regeneration including myostatin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue Myogenin [ Time Frame: 8 weeks ]
    Modulators of skeletal muscle regeneration by Western will include myogenin will be assessed using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue Myf5 [ Time Frame: 8 weeks ]
    Modulators of skeletal muscle regeneration My5 will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue MyoD [ Time Frame: 8 weeks ]
    Modulators of skeletal muscle regeneration MyoD will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue MEF2a [ Time Frame: 8 weeks ]
    Modulators of skeletal muscle regeneration MEF2a will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue dysferlin [ Time Frame: 8 weeks ]
    Structure associated indicators including dysferlin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue utrophin [ Time Frame: 8 weeks ]
    Structure associated indicators including utrophin will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
  • Muscle Tissue creatine Kinase (intracellular) [ Time Frame: 8 weeks ]
    Structure associated indicators including intracellular creatine kinase will be assessed by Western using relative band intensities of the pre-treatment and post-treatment specimens with digitally quantified using ImageJ software).
Efficacy Primary Endpoint: Evaluation of (-)-epicatechin on blood and muscle tissue markers of mitochondrial biogenesis and muscle regeneration in adults with Becker muscular dystrophy. [ Time Frame: 8 weeks ]
Treatment with 8 weeks of (-)- epicatechin 100mg daily will induce mitochondrial biogenesis, muscle regeneration, and improved histological appearance in sarcomere morphology.
Complete list of historical versions of study NCT01856868 on ClinicalTrials.gov Archive Site
  • -(-)Epicatechin Pharmacokinetics [ Time Frame: 8 Weeks ]
    Pharmacokinetics sequentially after dosing will be measured.
  • Safety Laboratory Assessments [ Time Frame: 8 weeks ]
    Standard safety monitoring of plasma hematologic, hepatologic, renal and metabolic parameters will be assessed.
  • Muscle Strength [ Time Frame: 8 weeks ]
    Knee extension and elbow flexion will assessed using an isokinetic dynamometer
  • Muscle Function (Endurance) [ Time Frame: 8 weeks ]
    Muscle function will be assessed by measuring the 6-minute walk distance
  • Muscle Function (Burst)_ [ Time Frame: 8 weeks ]
    Muscle burst function will b e assessed by time function tests including stand from supine, 4-stair climb and 10 meter run/wlak
  • Efficacy Secondary Endpoints: Evaluation of the effects of (-)-epicatechin on exercise capacity in adults with Becker muscular dystrophy. [ Time Frame: 8 Weeks ]
    Individuals with Becker muscular dystrophy who receive 100mg/day of (-)-epicatechin will demonstrate improved exercise performance and strength that is associated with increases in mitochondrial biogenesis and muscle regeneration.
  • Safety Secondary Endpoints: Evaluation of safety and pharmacokinetic profiles of (-)-epicatechin in adults with Becker muscular dystrophy. [ Time Frame: 8 weeks ]
    Assessments of safety will include a standard clinical safety panel including hematologic, hepatologic, renal and metabolic profiles. Pharmacokinetic studies will include repeat assessments of trough, 2 hour-post (peak) and 4-hour post dose (-)-epicatechin levels.
Not Provided
Pilot Biomarker Endpoints: Pilot evaluation of disease- and epicatechin-specific circulating mRNA and miRNA blood profiles as pilot biomarkers for monitoring treatment efficacy. [ Time Frame: 8 weeks ]
Epicatechin stimulates follistatin expression in tissue and blood. In addition to its effects on muscle regeneration, follistatin is known to exert anti-inflammatory and anti-fibrotic effects via antagonism of activin and myostatin.
 
Use of (-)-Epicatechin in the Treatment of Becker Muscular Dystrophy (Pilot Study)
An Open-label Pilot Study of Purified Tea-derived Epicatechin to Improve Mitochondrial Function, Strength and Skeletal Muscle Exercise Response in Becker Muscular Dystrophy.
(-)-Epicatechin will be evaluated for the treatment of progressive muscle loss and impaired skeletal muscle function in Becker Muscular Dystrophy (BMD) patients.

This is a proof-of-concept phase 1/2a pilot and endpoint development study that is designed to provide initial evidence of biological activity of (-)-epicatechin. Primary endpoints include initial assessment of tissue-specific evidence of efficacy from muscle biopsy samples. Secondary endpoints include measures of strength and physical function, and safety and adverse event data. Pilot endpoints include assessment of mRNA and miRNA peripheral blood profiles and validation of non-invasive near-infrared spectroscopy (NIRS) muscle perfusion studies during exercise and a recumbent cycle exercise test that may be employed as endpoints in future clinical trials.

This single center open-label pilot study will enroll 10 adults with genetically-confirmed Becker muscular dystrophy, who will receive the purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. After screening visits, participants will be enrolled in the study if they meet all inclusion criteria. They will be evaluated at baseline and at screening, day 1, and weeks 1, 2, 4 and 8.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Becker Muscular Dystrophy
Drug: (-)-epicatechin
purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Other Name: dietary supplement
Experimental: Treatment with Epicatechin
Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Intervention: Drug: (-)-epicatechin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
Same as current
October 2018
October 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male
  • Age 18 years to 60 years
  • Average to low daily physical activity
  • Ability to ambulate for 75 meters without assistive devices
  • Diagnosis of BMD confirmed by at least one the following:

    • Dystrophin immunofluorescence and/or immunoblot showing partial dystrophin deficiency, and clinical picture consistent with typical BMD, or
    • Gene deletions test positive (missing one or more exons) of the dystrophin gene, where reading frame can be predicted as 'in-frame', and clinical picture consistent with typical BMD, 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 BMD, with a typical clinical picture of BMD, or
    • Positive family history of BMD confirmed by one of the criteria listed above in a sibling or maternal uncle, and clinical picture typical of BMD.
  • Nutritional, herbal and antioxidant supplements taken with the intent of maintaining or improving skeletal muscle strength or functional mobility have been discontinued at least 2 weeks prior to screening (daily multivitamin use is acceptable).
  • Hematology profile within normal range
  • Baseline laboratory safety chemistry profile within normal range
  • No plan to change exercise regimen during study participation

Exclusion Criteria:

  • Currently enrolled 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.
  • Regular participation in vigorous exercise.
  • Symptomatic heart failure with cardiac ejection fraction <25%
Sexes Eligible for Study: Male
18 Years to 60 Years   (Adult)
No
Contact: Erica Goude, BA CCRP 916-734-0968 erica.goude@ucdmc.ucdavis.edu
United States
 
 
NCT01856868
454352
Not Provided
Not Provided
Not Provided
Craig McDonald, MD, University of California, Davis
Craig McDonald, MD
Cardero Therapeutics, Inc.
Principal Investigator: Craig M McDonald, MD University of California, Davis
Study Director: Erik K Henricson, MPH University of California, Davis
University of California, Davis
June 2018

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