Becker Muscular Dystrophy
Conditions
Keywords
BMD, Becker muscular dystrophy, epicatechin, clinical trial, neuromuscular disease
Brief summary
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.
Interventions
DRUG(-)-Epicatechin
Sponsors
Cardero Therapeutics, Inc.
Craig McDonald, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
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%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Follistatin:Myostain Ratio | 48 weeks | Ratio of plasma follistatin to plasma myostatin |
| Plasma MMP-9 | 48 weeks | blood biomarker concentration |
| Plasma TNF-Alpha | 48 weeks | blood biomarker concentration |
| Plasma TGF-Beta | 48 weeks | blood biomarker concentration |
| Plasma Follistatin | 48 weeks | blood biomarker concentration |
| Plasma Myostatin | 48 weeks | blood biomarker concentration |
| Plasma Nitrates/ SNO | 48 weeks | blood biomarker concentration |
| Plasma BNP | 48 weeks | blood biomarker concentration |
| Plasma Creatine Kinase | 48 weeks | blood biomarker concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Graded Exercise Test Using a Recumbent Cycle Ergometer | baseline and at 2-minute intervals | blood lactate measured |
| 6-minute Walk Test | 48 weeks | Measurements recorded will include 25-meter split times and total distance traveled. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Proteomics | 48 weeks | Collection of plasma samples for proteomics analysis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (-)-epicatechin 50mg twice per day (100mg per day total dose)
(-)-Epicatechin | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Treatment | — |
|---|---|---|
| Age, Continuous | 54 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 2 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Plasma BNP
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma Creatine Kinase
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma Follistatin
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma Follistatin:Myostain Ratio
Ratio of plasma follistatin to plasma myostatin
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma MMP-9
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma Myostatin
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma Nitrates/ SNO
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma TGF-Beta
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Primary
Plasma TNF-Alpha
blood biomarker concentration
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Secondary
6-minute Walk Test
Measurements recorded will include 25-meter split times and total distance traveled.
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Secondary
Graded Exercise Test Using a Recumbent Cycle Ergometer
blood lactate measured
Time frame: baseline and at 2-minute intervals
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.
Other Pre-specified
Exploratory Proteomics
Collection of plasma samples for proteomics analysis.
Time frame: 48 weeks
Population: Due to lack of funding, only 2 participants could be enrolled. The number of evaluable patients was insufficient to perform analysis of this outcome measure.