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| Name | Class |
|---|---|
| Cardero Therapeutics, Inc. | INDUSTRY |
(-)-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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment with Epicatechin | Experimental | Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| (-)-epicatechin | Drug | purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| -(-)Epicatechin Pharmacokinetics | Pharmacokinetics sequentially after dosing will be measured. | 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. |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Craig M McDonald, MD | University of California, Davis | Principal Investigator |
| Erik K Henricson, MPH | University of California, Davis | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Davis | Sacramento | California | 95817 | United States |
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| Label | URL |
|---|---|
| UC Davis Neuromuscular Research Center | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment With Epicatechin | Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment With Epicatechin | Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | Baseline and 8 Weeks |
|
8 weeks
There were 12 adverse events in six participants reported and tracked during the 8-week treatment phase of the study. Seven of the 12 events were related or possibly related to the study biopsy procedure. All adverse events were followed until resolution.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment With Epicatechin | Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bruising at the biopsy site | Skin and subcutaneous tissue disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Craig McDonald, Professor and Chair | UC Davis Health | (916) 734-4293 | cmmcdonald@ucdavis.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 8, 2013 | Nov 22, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 24, 2014 | Apr 7, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| D009468 | Neuromuscular Diseases |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D002392 | Catechin |
| D019587 | Dietary Supplements |
| ID | Term |
|---|---|
| D002839 | Chromans |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
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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 |
| 8 weeks |
| Change From Baseline in Knee Extension at 8 Weeks | Knee extension will be assessed using an isokinetic dynamometer. | 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 | Baseline and 8 Weeks |
| Change From Baseline in Stand From Supine at 8 Weeks | Muscle burst function will be assessed by time function tests. | Baseline and 8 Weeks |
| Change From Baseline in Elbow Flexion at 8 Weeks | Elbow flexion will be assessed using an isokinetic dynamometer. | Baseline and 8 Weeks |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height (cm) | Mean | Standard Deviation | centimeters |
|
| Weight (kg) | Mean | Standard Deviation | kilograms |
|
| Forced Vital Capacity (%) | Mean | Standard Deviation | % |
|
| 6-Minute Walk Distance (m) | Mean | Standard Deviation | meters |
|
| Time to Stand (s) | Mean | Standard Deviation | seconds |
|
| Time to Climb 4 Stairs (s) | Mean | Standard Deviation | seconds |
|
| Time to Run 10m (s) | Mean | Standard Deviation | seconds |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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) . | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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. | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Primary | 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). | One participant sustained a fall at home that resulted in a minor injury just prior to the 8 week evaluation and declined undergoing the 8 week biopsy. Thus, only 6 participants were analyzed. | Posted | Mean | Standard Deviation | AU | 8 weeks |
|
|
|
|
| Secondary | -(-)Epicatechin Pharmacokinetics | Pharmacokinetics sequentially after dosing will be measured. | Sponsor did not perform PK analysis (samples were discarded) based on availability of other published data and switched to alternative enantiomer of epicatechin in subsequent studies. | Posted | 8 Weeks |
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
| Secondary | Change From Baseline in Knee Extension at 8 Weeks | Knee extension will be assessed using an isokinetic dynamometer. | One participant did not participate in the strength testing due to the advanced level of the disease. | Posted | Mean | Standard Error | pounds | Baseline and 8 Weeks |
|
|
|
|
| Secondary | Change From Baseline in 6-Minute Walk Distance at 8 Weeks | Muscle function will be assessed by measuring the 6-minute walk distance | One participant did not complete 8 Week exercise testing due to unrelated injury. | Posted | Mean | Standard Error | meters | Baseline and 8 Weeks |
|
|
|
|
| Secondary | Change From Baseline in Stand From Supine at 8 Weeks | Muscle burst function will be assessed by time function tests. | 1 participant was unable to perform the assessment due to his advanced disease. | Posted | Mean | Standard Deviation | seconds | Baseline and 8 Weeks |
|
|
|
| Secondary | Change From Baseline in Elbow Flexion at 8 Weeks | Elbow flexion will be assessed using an isokinetic dynamometer. | One participant did not participate in the strength testing due to the advanced level of the disease. | Posted | Mean | Standard Error | pounds | Baseline and 8 Weeks |
|
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| Non-biopsy-related flulike symptoms | General disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| suspected varicella (shingles) | Immune system disorders | Systematic Assessment |
|
| Muscle soreness | General disorders | Systematic Assessment |
|
| Intermittent headache | General disorders | Systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006571 |
| Heterocyclic Compounds |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |