(-)- Epicatechin Becker Muscular Dystrophy

UCD0115B: An Open-label Extension Study of Purified Epicatechin to Improve Mitochondrial Function, Strength and Skeletal Muscle Exercise Response in Becker Muscular Dystrophy

This is a 48-week open-label extension of our initial proof-of-concept study (UCD0113) in patients with Becker muscular dystrophy who participated in the earlier trial. This single center study will enroll up to 10 adults 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 screening, baseline, and weeks 4, 8, 12, 24, 16 and 48. The main criterion for success of the study will be presence of one or more biologic or strength and performance outcome measures that yield a response magnitude that allows for sufficient power in a Phase II B study with a sample size of 30 individuals.

Study Overview

• Status: Completed
• Conditions: Becker Muscular Dystrophy
• Intervention / Treatment: Drug: (-)-Epicatechin

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Prior participation in UCD0113 BMD epicatechin pilot study
• Male
• Age 18 years to 70 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.
• Hematology profile within normal range
• Baseline laboratory safety chemistry profile within normal range
• No plan to change exercise regimen during study participation
• 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).

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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; (-)-epicatechin 50mg twice per day (100mg per day total dose)	Drug: (-)-Epicatechin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Follistatin	blood biomarker concentration	48 weeks
Plasma Myostatin	blood biomarker concentration	48 weeks
Plasma Nitrates/ SNO	blood biomarker concentration	48 weeks
Plasma BNP	blood biomarker concentration	48 weeks
Plasma Creatine Kinase	blood biomarker concentration	48 weeks
Plasma MMP-9	blood biomarker concentration	48 weeks
Plasma TNF-Alpha	blood biomarker concentration	48 weeks
Plasma TGF-Beta	blood biomarker concentration	48 weeks
Plasma Follistatin:Myostain Ratio	Ratio of plasma follistatin to plasma myostatin	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graded Exercise Test Using a Recumbent Cycle Ergometer	blood lactate measured	baseline and at 2-minute intervals
6-minute Walk Test	Measurements recorded will include 25-meter split times and total distance traveled.	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Proteomics	Collection of plasma samples for proteomics analysis.	48 weeks

Collaborators and Investigators

• Sponsor: Craig McDonald, MD
• Collaborators: Cardero Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: July 28, 2017
• First Posted (Actual): August 2, 2017

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 22, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: clinical trial; Becker muscular dystrophy; BMD; neuromuscular disease; epicatechin
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 767161