Trial Outcomes & Findings for Use of (-)-Epicatechin in the Treatment of Becker Muscular Dystrophy (Pilot Study) (NCT NCT01856868)

NCT ID: NCT01856868

Last Updated: 2021-12-22

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 7 participants
• Primary outcome timeframe: Baseline and 8 Weeks
• Results posted on: 2021-12-22

Participant Flow

Participant milestones

Measure	Treatment With Epicatechin Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment With Epicatechin n=7 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Age, Continuous	46.6 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants
Height (cm)	179.2 centimeters STANDARD_DEVIATION 4.3 • n=5 Participants
Weight (kg)	83.2 kilograms STANDARD_DEVIATION 18.3 • n=5 Participants
Forced Vital Capacity (%)	93.4 % STANDARD_DEVIATION 12.5 • n=5 Participants
6-Minute Walk Distance (m)	372 meters STANDARD_DEVIATION 87.2 • n=5 Participants
Time to Stand (s)	5.5 seconds STANDARD_DEVIATION 2.3 • n=5 Participants
Time to Climb 4 Stairs (s)	7.4 seconds STANDARD_DEVIATION 7.4 • n=5 Participants
Time to Run 10m (s)	7.9 seconds STANDARD_DEVIATION 7.9 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 8 Weeks

Population: 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.

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.

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Change From Baseline in Muscle Tissue PGC1alpha (AU) at 8 Weeks Baseline	0.55 AU Standard Deviation 0.3
Change From Baseline in Muscle Tissue PGC1alpha (AU) at 8 Weeks 8 Weeks	0.86 AU Standard Deviation 0.17

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue AMPK at 8 Weeks Baseline	0.76 AU Standard Deviation 0.48
Mean Change From Baseline in Muscle Tissue AMPK at 8 Weeks Week 8	1.06 AU Standard Deviation 0.52

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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) .

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue LKB1 at 8 Weeks Baseline	0.67 AU Standard Deviation 0.17
Mean Change From Baseline in Muscle Tissue LKB1 at 8 Weeks Week 8	0.88 AU Standard Deviation 0.24

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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.

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Cristae-associated Mitofillin Levels at 8 Weeks Baseline	1.05 AU Standard Deviation 0.36
Mean Change From Baseline in Cristae-associated Mitofillin Levels at 8 Weeks Week 8	1.33 AU Standard Deviation 0.3

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue Follistatin at 8 Weeks Baseline	0.83 AU Standard Deviation 0.37
Mean Change From Baseline in Muscle Tissue Follistatin at 8 Weeks Week 8	1.11 AU Standard Deviation 0.36

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue Myostatin at 8 Weeks Baseline	0.79 AU Standard Deviation 0.3
Mean Change From Baseline in Muscle Tissue Myostatin at 8 Weeks Week 8	0.51 AU Standard Deviation 0.25

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue Myogenin at 8 Weeks Baseline	0.89 AU Standard Deviation 0.18
Mean Change From Baseline in Muscle Tissue Myogenin at 8 Weeks Week 8	1.20 AU Standard Deviation 0.19

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue Myf5 at 8 Weeks Baseline	1.07 AU Standard Deviation 0.08
Mean Change From Baseline in Muscle Tissue Myf5 at 8 Weeks Week 8	1.232 AU Standard Deviation 0.13

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue MyoD at 8 Weeks Baseline	0.87 AU Standard Deviation 0.34
Mean Change From Baseline in Muscle Tissue MyoD at 8 Weeks Week 8	1.21 AU Standard Deviation 0.34

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue MEF2a at 8 Weeks Baseline	0.63 AU Standard Deviation 0.15
Mean Change From Baseline in Muscle Tissue MEF2a at 8 Weeks Week 8	0.78 AU Standard Deviation 0.12

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue Dysferlin at 8 Weeks Baseline	0.65 AU Standard Deviation 0.26
Mean Change From Baseline in Muscle Tissue Dysferlin at 8 Weeks Week 8	0.91 AU Standard Deviation 0.25

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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).

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Mean Change From Baseline in Muscle Tissue Utrophin at 8 Weeks Baseline	0.63 AU Standard Deviation 0.27
Mean Change From Baseline in Muscle Tissue Utrophin at 8 Weeks Week 8	0.8 AU Standard Deviation 0.19

SECONDARY outcome

Timeframe: 8 Weeks

Population: 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.

Pharmacokinetics sequentially after dosing will be measured.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 weeks

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.

Outcome measures

Measure	Treatment With Epicatechin n=7 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Participants With Abnormal Treatment-Related Laboratory Assessments	0 Participants

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: One participant did not participate in the strength testing due to the advanced level of the disease.

Knee extension will be assessed using an isokinetic dynamometer.

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Change From Baseline in Knee Extension at 8 Weeks Baseline	48.1 pounds Standard Error 42.6
Change From Baseline in Knee Extension at 8 Weeks Change from Baseline at 8 Weeks	-1.82 pounds Standard Error 2.51

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: One participant did not complete 8 Week exercise testing due to unrelated injury.

Muscle function will be assessed by measuring the 6-minute walk distance

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Change From Baseline in 6-Minute Walk Distance at 8 Weeks	11.2 meters Standard Error 16.6

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: 1 participant was unable to perform the assessment due to his advanced disease.

Muscle burst function will be assessed by time function tests.

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Change From Baseline in Stand From Supine at 8 Weeks Baseline	9.621667 seconds Standard Deviation 10.19124
Change From Baseline in Stand From Supine at 8 Weeks Week 8	12.145 seconds Standard Deviation 10.12084

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: One participant did not participate in the strength testing due to the advanced level of the disease.

Elbow flexion will be assessed using an isokinetic dynamometer.

Outcome measures

Measure	Treatment With Epicatechin n=6 Participants Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Change From Baseline in Elbow Flexion at 8 Weeks Baseline	27.7 pounds Standard Error 11.1
Change From Baseline in Elbow Flexion at 8 Weeks Change from Baseline at 8 Weeks	5.33 pounds Standard Error 3.79

Adverse Events

Treatment With Epicatechin

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment With Epicatechin n=6 participants at risk Purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks. (-)-epicatechin: purified nutritional extract (-)-epicatechin 100mg/day orally for 8 weeks.
Skin and subcutaneous tissue disorders Bruising at the biopsy site	100.0% 6/6 • Number of events 6 • 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.
General disorders Non-biopsy-related flulike symptoms	33.3% 2/6 • Number of events 2 • 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.
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Number of events 1 • 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.
Immune system disorders suspected varicella (shingles)	16.7% 1/6 • Number of events 1 • 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.
General disorders Muscle soreness	16.7% 1/6 • Number of events 1 • 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.
General disorders Intermittent headache	16.7% 1/6 • Number of events 1 • 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.

Additional Information

Dr. Craig McDonald, Professor and Chair

UC Davis Health

Phone: (916) 734-4293

Email: cmmcdonald@ucdavis.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place