Plus Epicatechin Duchenne Muscular Dystrophy in Non-ambulatory Adolescents

NCT ID: NCT02964377

Last Updated: 2021-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-07-31

Brief Summary

This single center open-label pilot study will enroll 15 non-ambulatory children with Duchenne muscular dystrophy at least 8 years of age and who demonstrate pre-clinical cardiomyopathy (defined as a cardiac ejection fraction >55% with abnormal LV strain by cardiac MRI). They will receive (+)-epicatechin at one of three doses during an 8-week dose-ranging study with assessments at baseline, 2 Weeks, 4weeks, and 8 weeks. The study will determine optimal dosing for future cardiac efficacy studies based on serum / plasma biomarker response using follistatin: myostatin ratio, nitrite/nitrate ratio, cardiac troponins and cardiac BNP. Secondary endpoints will include additional biomarker assessments by SOMAscanTM, cardiac functional evaluations by cardiac MRI (LV strain), and echocardiogram (LV strain by speckle tracking) and measures of strength, range of motion and mobility, and clinical safety assessments. Results of secondary endpoint analysis will be used to refine design of subsequent clinical trials powered to detect changes in clinical outcomes.

Conditions

Duchenne Muscular Dystrophy

Keywords

Pediatric; muscle disease; Duchenne muscular dystrophy; cardiomyopathy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

8-weeks open-label (+)- Epicatechin at 25mg/day twice per day,

Group Type: EXPERIMENTAL

(+)- Epicatechin

Intervention Type: DRUG

Cohort 2

8-weeks open-label (+)- Epicatechin at 25mg/day three times per day

Group Type: EXPERIMENTAL

(+)- Epicatechin

Intervention Type: DRUG

Cohort 3

8-weeks open-label (+)- Epicatechin at 75mg/day at two times per day

Group Type: EXPERIMENTAL

(+)- Epicatechin

Intervention Type: DRUG

Interventions

(+)- Epicatechin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male
• Age 8 years to 17 years
• Non-Ambulatory (unable to complete 10m run/walk under 10s)
• Weight </=100Kg
• Diagnosis of DMD confirmed by at least one the following:

• Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, or
• Gene deletions test positive (missing one or more exons) of the dystrophin gene, where reading frame can be predicted as 'out-of-frame', and clinical picture consistent with typical DMD, 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 DMD, with a typical clinical picture of DMD, or
• Positive family history of DMD confirmed by one of the criteria listed above in a sibling or maternal uncle, and clinical picture typical of DMD.
• Cardiac ejection fraction >55% on echocardiogram
• Use of nutritional, herbal and antioxidant supplements taken with the intent of maintaining or improving skeletal muscle strength or functional mobility has been discontinued at least 4 weeks prior to screening (daily multivitamin use is acceptable).
• Glucocorticoid therapy, if used, must have a stable weight-based dose for at least 3 months prior to enrollment
• Cardiac therapy, if used, includes prophylactic ACE inhibitors, aldosterone receptor antagonists (e.g.

spironolactone, eplerenone, etc.), and/or beta-blocker therapy, and must be stable for 3 months prior to enrollment.

• Hematology profile within normal range.
• Baseline laboratory safety chemistry profile within typical range for DMD (elevated ALT / AST acceptable in the absence of elevated GGT, elevated CK acceptable).

Exclusion Criteria

• Inability to complete cardiac or strength, range of motion and mobility assessments per protocol
• Current enrollment 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.
• Cardiac symptoms that, in the opinion of the investigator, may be suggestive of imminent moderate to severe cardiac events, irrespective of LVEF.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Cardero Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

Craig McDonald, MD

OTHER

Sponsor Role: lead

Responsible Party

Craig McDonald, MD

Professor and Chair of Department of Physical Rehabilitation

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

UC Davis Medical Center

Sacramento, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

951753

Identifier Type: -

Identifier Source: org_study_id