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

NCT01856868 | Completed Phase 1 Results

• 1 other identifier: 454352
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Becker Muscular Dystrophy

Keywords

BMD; Becker muscular dystrophy; epicatechin; clinical trial; neuromuscular disease

Outcome Measures

Primary Outcomes (12)

• 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.

  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).

  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) .

  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.

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  8 weeks

Secondary Outcomes (6)

• -(-)Epicatechin Pharmacokinetics

  8 Weeks

• Participants With Abnormal Treatment-Related Laboratory Assessments

  8 weeks

• Change From Baseline in Knee Extension at 8 Weeks

  Baseline and 8 Weeks

• Change From Baseline in 6-Minute Walk Distance at 8 Weeks

  Baseline and 8 Weeks

• Change From Baseline in Stand From Supine at 8 Weeks

  Baseline and 8 Weeks

Study Arms (1)

Treatment with Epicatechin

EXPERIMENTAL

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

Drug: (-)-epicatechin

Interventions

(-)-epicatechin DRUG

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

Also known as: dietary supplement

Treatment with Epicatechin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Craig McDonald, MD: lead
• Cardero Therapeutics, Inc.: collaborator

Study Sites (1)

University of California, Davis

Sacramento, California, 95817, United States

Location

Related Links

• UC Davis Neuromuscular Research Center

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Neuromuscular Diseases

Interventions

Catechin; Dietary Supplements

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Chromans; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Flavonoids; Chromones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Limitations and Caveats

Limitations of this study include the small number of subjects, the open-label design, and the use of within-subjects controls with BMD rather than a placebo-treated group in a randomized, double-blind, placebo-controlled trial design.

Results Point of Contact

• Title: Dr. Craig McDonald, Professor and Chair
• Organization: UC Davis Health

cmmcdonald@ucdavis.edu

(916) 734-4293

Study Officials

• Craig M McDonald, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Erik K Henricson, MPH

  University of California, Davis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor and Chairman, Department of Physical Medicine and Rehabilitation

Study Record Dates

• First Submitted: May 9, 2013
• First Posted: May 17, 2013
• Study Start: May 1, 2013
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: December 22, 2021
• Results First Posted: December 22, 2021

Record last verified: 2021-11

Locations

US (1)