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Trial record 21 of 96 for:    Recruiting, Not yet recruiting, Available Studies | "Muscular Dystrophies"

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

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ClinicalTrials.gov Identifier: NCT01856868
Recruitment Status : Recruiting
First Posted : May 17, 2013
Last Update Posted : June 8, 2018
Sponsor:
Collaborator:
Cardero Therapeutics, Inc.
Information provided by (Responsible Party):
Craig McDonald, MD, University of California, Davis

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

Condition or disease Intervention/treatment Phase
Becker Muscular Dystrophy Drug: (-)-epicatechin Phase 1 Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2013
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018


Arm Intervention/treatment
Experimental: Treatment with Epicatechin
Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Drug: (-)-epicatechin
purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Other Name: dietary supplement




Primary Outcome Measures :
  1. Muscle tissue PGC1alpha [ Time Frame: 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 and post-treatment specimens with digitally quantified using ImageJ software)

  2. Muscle tissue AMPK [ Time Frame: 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).

  3. Muscle Tissue LKB1 [ Time Frame: 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) .

  4. Cristae-associated Mitofilin levels [ Time Frame: 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).

  5. Muscle Tissue Follistatin [ Time Frame: 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).

  6. Muscle Tissue Myostatin [ Time Frame: 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).

  7. Muscle Tissue Myogenin [ Time Frame: 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. Muscle Tissue Myf5 [ Time Frame: 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).

  9. Muscle Tissue MyoD [ Time Frame: 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).

  10. Muscle Tissue MEF2a [ Time Frame: 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).

  11. Muscle Tissue dysferlin [ Time Frame: 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).

  12. Muscle Tissue utrophin [ Time Frame: 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).

  13. Muscle Tissue creatine Kinase (intracellular) [ Time Frame: 8 weeks ]
    Structure associated indicators including intracellular creatine kinase 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 :
  1. -(-)Epicatechin Pharmacokinetics [ Time Frame: 8 Weeks ]
    Pharmacokinetics sequentially after dosing will be measured.

  2. Safety Laboratory Assessments [ Time Frame: 8 weeks ]
    Standard safety monitoring of plasma hematologic, hepatologic, renal and metabolic parameters will be assessed.

  3. Muscle Strength [ Time Frame: 8 weeks ]
    Knee extension and elbow flexion will assessed using an isokinetic dynamometer

  4. Muscle Function (Endurance) [ Time Frame: 8 weeks ]
    Muscle function will be assessed by measuring the 6-minute walk distance

  5. Muscle Function (Burst)_ [ Time Frame: 8 weeks ]
    Muscle burst function will b e assessed by time function tests including stand from supine, 4-stair climb and 10 meter run/wlak



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01856868


Contacts
Contact: Erica Goude, BA CCRP 916-734-0968 erica.goude@ucdmc.ucdavis.edu

Locations
United States, California
University of California, Davis Recruiting
Sacramento, California, United States, 95817
Contact: Erica Goude, BA CCRP    916-734-0968    erica.goude@ucdmc.ucdavis.edu   
Principal Investigator: Craig M McDonald, MD         
Sub-Investigator: Erik K Henricson, MPH         
Sub-Investigator: Richard T Abresch, MS         
Sub-Investigator: Frank Sharp, MD         
Sub-Investigator: Glenn Jickling, MD         
Sub-Investigator: Bjorn E Oskarsson, MD         
Sponsors and Collaborators
Craig McDonald, MD
Cardero Therapeutics, Inc.
Investigators
Principal Investigator: Craig M McDonald, MD University of California, Davis
Study Director: Erik K Henricson, MPH University of California, Davis

Additional Information:
Responsible Party: Craig McDonald, MD, Professor and Chairman, Department of Physical Medicine and Rehabilitation, University of California, Davis
ClinicalTrials.gov Identifier: NCT01856868     History of Changes
Other Study ID Numbers: 454352
First Posted: May 17, 2013    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

Keywords provided by Craig McDonald, MD, University of California, Davis:
BMD
Becker muscular dystrophy
epicatechin
clinical trial
neuromuscular disease

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked