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

Primary Purpose

Becker Muscular Dystrophy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
(-)-epicatechin
Sponsored by
Craig McDonald, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Becker Muscular Dystrophy focused on measuring BMD, Becker muscular dystrophy, epicatechin, clinical trial, neuromuscular disease

Eligibility Criteria

18 Years - 60 Years (Adult)MaleDoes not accept healthy volunteers

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%

Sites / Locations

  • University of California, Davis

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment with Epicatechin

Arm Description

Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.

Outcomes

Primary Outcome Measures

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.
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).
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) .
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.
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).
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).
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).
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).
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).
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).
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).
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).

Secondary Outcome Measures

-(-)Epicatechin Pharmacokinetics
Pharmacokinetics sequentially after dosing will be measured.
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.
Change From Baseline in Knee Extension at 8 Weeks
Knee extension will be assessed using an isokinetic dynamometer.
Change From Baseline in 6-Minute Walk Distance at 8 Weeks
Muscle function will be assessed by measuring the 6-minute walk distance
Change From Baseline in Stand From Supine at 8 Weeks
Muscle burst function will be assessed by time function tests.
Change From Baseline in Elbow Flexion at 8 Weeks
Elbow flexion will be assessed using an isokinetic dynamometer.

Full Information

First Posted
May 9, 2013
Last Updated
November 22, 2021
Sponsor
Craig McDonald, MD
Collaborators
Cardero Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01856868
Brief Title
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

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
September 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Craig McDonald, MD
Collaborators
Cardero Therapeutics, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Becker Muscular Dystrophy
Keywords
BMD, Becker muscular dystrophy, epicatechin, clinical trial, neuromuscular disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment with Epicatechin
Arm Type
Experimental
Arm Description
Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
(-)-epicatechin
Other Intervention Name(s)
dietary supplement
Intervention Description
purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Primary Outcome Measure Information:
Title
Change From Baseline in Muscle Tissue PGC1alpha (AU) at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue AMPK at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue LKB1 at 8 Weeks
Description
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
Title
Mean Change From Baseline in Cristae-associated Mitofillin Levels at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue Follistatin at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue Myostatin at 8 Weeks
Description
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).
Time Frame
8 weeks
Title
Mean Change From Baseline in Muscle Tissue Myogenin at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue Myf5 at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue MyoD at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue MEF2a at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue Dysferlin at 8 Weeks
Description
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
Title
Mean Change From Baseline in Muscle Tissue Utrophin at 8 Weeks
Description
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
Secondary Outcome Measure Information:
Title
-(-)Epicatechin Pharmacokinetics
Description
Pharmacokinetics sequentially after dosing will be measured.
Time Frame
8 Weeks
Title
Participants With Abnormal Treatment-Related Laboratory Assessments
Description
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
Title
Change From Baseline in Knee Extension at 8 Weeks
Description
Knee extension will be assessed using an isokinetic dynamometer.
Time Frame
Baseline and 8 Weeks
Title
Change From Baseline in 6-Minute Walk Distance at 8 Weeks
Description
Muscle function will be assessed by measuring the 6-minute walk distance
Time Frame
Baseline and 8 Weeks
Title
Change From Baseline in Stand From Supine at 8 Weeks
Description
Muscle burst function will be assessed by time function tests.
Time Frame
Baseline and 8 Weeks
Title
Change From Baseline in Elbow Flexion at 8 Weeks
Description
Elbow flexion will be assessed using an isokinetic dynamometer.
Time Frame
Baseline and 8 Weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig M McDonald, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Erik K Henricson, MPH
Organizational Affiliation
University of California, Davis
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.ucdmc.ucdavis.edu/pmr/research/Index.html
Description
UC Davis Neuromuscular Research Center

Learn more about this trial

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

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