Clinical trial NCT01856868: Use of (-)-Epicatechin in the Treatment of Becker Muscular Dystrophy (Pilot Study)
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Becker Muscular Dystrophy
Keywords: BMD
Becker muscular dystrophy
epicatechin
clinical trial
neuromuscular disease
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Cardero Therapeutics, Inc.
First posted: 2013-05-17
Enrollment: 7
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: (-)-Epicatechin will be evaluated for the treatment of progressive muscle loss and impaired skeletal muscle function in Becker Muscular Dystrophy (BMD) patients.

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.

Eligibility criteria: 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%

Primary outcomes:
measure: Change From Baseline in Muscle Tissue PGC1alpha (AU) at 8 Weeks
timeFrame: Baseline and 8 Weeks
measure: Mean Change From Baseline in Muscle Tissue AMPK at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue LKB1 at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Cristae-associated Mitofillin Levels at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue Follistatin at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue Myostatin at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue Myogenin at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue Myf5 at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue MyoD at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue MEF2a at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue Dysferlin at 8 Weeks
timeFrame: 8 weeks
measure: Mean Change From Baseline in Muscle Tissue Utrophin at 8 Weeks
timeFrame: 8 weeks
Secondary outcomes:
measure: -(-)Epicatechin Pharmacokinetics
timeFrame: 8 Weeks
measure: Participants With Abnormal Treatment-Related Laboratory Assessments
timeFrame: 8 weeks
measure: Change From Baseline in Knee Extension at 8 Weeks
timeFrame: Baseline and 8 Weeks
measure: Change From Baseline in 6-Minute Walk Distance at 8 Weeks
timeFrame: Baseline and 8 Weeks
measure: Change From Baseline in Stand From Supine at 8 Weeks
timeFrame: Baseline and 8 Weeks
measure: Change From Baseline in Elbow Flexion at 8 Weeks
timeFrame: Baseline and 8 Weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis
state: California
Study officials:
affiliation: University of California, Davis
name: Craig M McDonald, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Erik K Henricson, MPH
role: STUDY_DIRECTOR
References: