- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01856868
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Sacramento, California, United States, 95817
- University of California, Davis
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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%
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment with Epicatechin
Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
|
purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Muscle Tissue PGC1alpha (AU) at 8 Weeks
Time Frame: Baseline and 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 (Baseline) and post-treatment (8 Weeks) specimens with digitally quantified using ImageJ software.
|
Baseline and 8 Weeks
|
Mean Change From Baseline in Muscle Tissue AMPK at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue LKB1 at 8 Weeks
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) .
|
8 weeks
|
Mean Change From Baseline in Cristae-associated Mitofillin Levels at 8 Weeks
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.
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue Follistatin at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue Myostatin at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue Myogenin at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue Myf5 at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue MyoD at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue MEF2a at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue Dysferlin at 8 Weeks
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).
|
8 weeks
|
Mean Change From Baseline in Muscle Tissue Utrophin at 8 Weeks
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).
|
8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
-(-)Epicatechin Pharmacokinetics
Time Frame: 8 Weeks
|
Pharmacokinetics sequentially after dosing will be measured.
|
8 Weeks
|
Participants With Abnormal Treatment-Related Laboratory Assessments
Time Frame: 8 weeks
|
Standard safety monitoring of plasma hematologic, hepatologic, renal and metabolic parameters will be assessed.
Abnormal will be defined as values outside of typical range for patients with Becker Muscular Dystrophy.
|
8 weeks
|
Change From Baseline in Knee Extension at 8 Weeks
Time Frame: Baseline and 8 Weeks
|
Knee extension will be assessed using an isokinetic dynamometer.
|
Baseline and 8 Weeks
|
Change From Baseline in 6-Minute Walk Distance at 8 Weeks
Time Frame: Baseline and 8 Weeks
|
Muscle function will be assessed by measuring the 6-minute walk distance
|
Baseline and 8 Weeks
|
Change From Baseline in Stand From Supine at 8 Weeks
Time Frame: Baseline and 8 Weeks
|
Muscle burst function will be assessed by time function tests.
|
Baseline and 8 Weeks
|
Change From Baseline in Elbow Flexion at 8 Weeks
Time Frame: Baseline and 8 Weeks
|
Elbow flexion will be assessed using an isokinetic dynamometer.
|
Baseline and 8 Weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Craig M McDonald, MD, University of California, Davis
- Study Director: Erik K Henricson, MPH, University of California, Davis
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 454352
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Becker Muscular Dystrophy
-
Virginia Commonwealth UniversityEdgewise Therapeutics, Inc.RecruitingMuscular Dystrophies | Becker Muscular Dystrophy | Muscular Dystrophy in Children | Muscular Dystrophy, BeckerUnited States, United Kingdom
-
Boston Children's HospitalNational Institute of Neurological Disorders and Stroke (NINDS)RecruitingLimb-girdle Muscular Dystrophy | Neuromuscular; Disorder, Hereditary | Duchenne/Becker Muscular DystrophyUnited States
-
University Children's Hospital, ZurichUnknownDuchenne / Becker Muscular DystrophySwitzerland
-
Gaziosmanpasa Research and Education HospitalCompletedDuchenne or Becker Muscular DystrophyTurkey
-
ItalfarmacoCompletedDuchenne and Becker Muscular Dystrophy | Polycytemia VeraCanada
-
InCor Heart InstituteUniversity of Sao Paulo; Federal University of Minas GeraisCompletedMyocardial Fibrosis | Muscular Dystrophies
-
Wyeth is now a wholly owned subsidiary of PfizerCompletedBecker Muscular Dystrophy | Facioscapulohumeral Muscular Dystrophy | Limb-Girdle Muscular DystrophyUnited States
-
University of North Carolina, Chapel HillNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other collaboratorsCompletedMuscular Dystrophies | Duchenne Muscular Dystrophy | Becker Muscular Dystrophy | Limb-Girdle Muscular DystrophyUnited States
-
IRCCS Eugenio MedeaRecruitingMuscular Dystrophies | Becker Muscular Dystrophy | Limb Girdle Muscular Dystrophy | Facio-Scapulo-Humeral DystrophyItaly
-
RSPR Pharma ABCompletedDuchenne Muscular Dystrophy | Becker Muscular DystrophySweden
Clinical Trials on (-)-epicatechin
-
Veterans Medical Research FoundationUniversity of California, San Diego; National Institutes of Health (NIH); National... and other collaboratorsCompletedPre-diabetesUnited States
-
Quadram Institute BioscienceDanisco; Coressence LTDCompleted
-
University of ReadingCompletedVasodilationUnited Kingdom
-
University of California, San DiegoThe Hershey CompanyCompletedHeart Failure | Type 2 DiabetesUnited States
-
Ralitza GavrilovaCardero Therapeutics, Inc.Completed
-
University of California, DavisCompletedCollagen SynthesisUnited States
-
Prof. Dominique de Quervain, MDCompleted
-
Veterans Medical Research FoundationUniversity of California, San Diego; National Institutes of Health (NIH); National... and other collaboratorsCompletedPre-diabetesUnited States
-
Craig McDonald, MDCardero Therapeutics, Inc.CompletedDuchenne Muscular DystrophyUnited States
-
Craig McDonald, MDCardero Therapeutics, Inc.Completed