(-)- Epicatechin Becker Muscular Dystrophy

• Sponsor: Craig McDonald, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT03236662
• Collaborator: Cardero Therapeutics, Inc. (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 13
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Becker Muscular Dystrophy	Drug: (-)-Epicatechin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: UCD0115B: An Open-label Extension Study of Purified Epicatechin to Improve Mitochondrial Function, Strength and Skeletal Muscle Exercise Response in Becker Muscular Dystrophy
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (-)-epicatechin 50mg twice per day (100mg per day total dose)	Drug: (-)-Epicatechin

Outcome Measures

Primary Outcome Measures

1. Plasma Follistatin [48 weeks]

   blood biomarker concentration

2. Plasma Myostatin [48 weeks]

   blood biomarker concentration

3. Plasma Nitrates/ SNO [48 weeks]

   blood biomarker concentration

4. Plasma BNP [48 weeks]

   blood biomarker concentration

5. Plasma Creatine Kinase [48 weeks]

   blood biomarker concentration

6. Plasma MMP-9 [48 weeks]

   blood biomarker concentration

7. Plasma TNF-Alpha [48 weeks]

   blood biomarker concentration

8. Plasma TGF-Beta [48 weeks]

   blood biomarker concentration

9. Plasma Follistatin:Myostain Ratio [48 weeks]

   Ratio of plasma follistatin to plasma myostatin

Secondary Outcome Measures

1. Graded Exercise Test Using a Recumbent Cycle Ergometer [baseline and at 2-minute intervals]

   blood lactate measured

2. 6-minute Walk Test [48 weeks]

   Measurements recorded will include 25-meter split times and total distance traveled.

Other Outcome Measures

1. Exploratory Proteomics [48 weeks]

   Collection of plasma samples for proteomics analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Male
• Accepts 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%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis Medical Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• Craig McDonald, MD
• Cardero Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 15, 2015
• Informed Consent Form - Aug 20, 2015

More Information

Publications

None provided.

• Responsible Party: Craig McDonald, MD, Principal Investigator, University of California, Davis
• ClinicalTrials.gov Identifier: NCT03236662
• Other Study ID Numbers: 767161
• First Posted: Aug 2, 2017
• Last Update Posted: Nov 24, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Craig McDonald, MD, Principal Investigator, University of California, Davis: BMD; Becker muscular dystrophy; epicatechin; clinical trial; neuromuscular disease
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Overall Participants	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Plasma Follistatin
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

2. Primary Outcome

Title	Plasma Myostatin
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

3. Primary Outcome

Title	Plasma Nitrates/ SNO
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

4. Primary Outcome

Title	Plasma BNP
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

5. Primary Outcome

Title	Plasma Creatine Kinase
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

6. Primary Outcome

Title	Plasma MMP-9
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

7. Primary Outcome

Title	Plasma TNF-Alpha
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

8. Primary Outcome

Title	Plasma TGF-Beta
Description	blood biomarker concentration
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

9. Primary Outcome

Title	Plasma Follistatin:Myostain Ratio
Description	Ratio of plasma follistatin to plasma myostatin
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

10. Secondary Outcome

Title	Graded Exercise Test Using a Recumbent Cycle Ergometer
Description	blood lactate measured
Time Frame	baseline and at 2-minute intervals

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

11. Secondary Outcome

Title	6-minute Walk Test
Description	Measurements recorded will include 25-meter split times and total distance traveled.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

12. Other Pre-specified Outcome

Title	Exploratory Proteomics
Description	Collection of plasma samples for proteomics analysis.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
Measure Participants	0

Adverse Events

Time Frame	48 weeks
Arm/Group Title	Treatment
Arm/Group Description	(-)-epicatechin 50mg twice per day (100mg per day total dose) (-)-Epicatechin
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

Small number of subjects analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.