(-)-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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
University of California, Davis
Sacramento, California, United States
Change From Baseline in Muscle Tissue PGC1alpha (AU) at 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.
Time frame: Baseline and 8 Weeks
Mean Change From Baseline in Muscle Tissue AMPK at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue LKB1 at 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) .
Time frame: 8 weeks
Mean Change From Baseline in Cristae-associated Mitofillin Levels at 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.
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue Follistatin at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue Myostatin at 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).
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Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue Myogenin at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue Myf5 at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue MyoD at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue MEF2a at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue Dysferlin at 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).
Time frame: 8 weeks
Mean Change From Baseline in Muscle Tissue Utrophin at 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).
Time frame: 8 weeks
-(-)Epicatechin Pharmacokinetics
Pharmacokinetics sequentially after dosing will be measured.
Time frame: 8 Weeks
Participants With Abnormal Treatment-Related Laboratory Assessments
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.
Time frame: 8 weeks
Change From Baseline in Knee Extension at 8 Weeks
Knee extension will be assessed using an isokinetic dynamometer.
Time frame: Baseline and 8 Weeks
Change From Baseline in 6-Minute Walk Distance at 8 Weeks
Muscle function will be assessed by measuring the 6-minute walk distance
Time frame: Baseline and 8 Weeks
Change From Baseline in Stand From Supine at 8 Weeks
Muscle burst function will be assessed by time function tests.
Time frame: Baseline and 8 Weeks
Change From Baseline in Elbow Flexion at 8 Weeks
Elbow flexion will be assessed using an isokinetic dynamometer.
Time frame: Baseline and 8 Weeks