CoQ10 and Prednisone in Non-Ambulatory DMD

Study Overview
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Brief Summary
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This study will help determine if CoQ10 and prednisone, alone and as a combination decrease the decline in cardiopulmonary and skeletal muscle function that occurs in the wheelchair confined phase of DMD. Participants who are enrolled in this study should not have taken any corticosteroids within the last six months. This is a 13-month, prospective, randomized study comparing a daily prednisone arm (0.75mg/kg/day), a CoQ10 arm (serum of greater than 2.5 ug/mL) and a combination arm (prednisone and CoQ10) with an enhanced standard of care arm in wheelchair confined males age 10 to 18 years with an established DMD diagnosis.

Detailed Description
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Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy affecting 1:3500 male births worldwide. Despite an increase in our understanding of the disorder since the discovery and characterization of the causative gene and its product dystrophin in 1987, current therapeutic management remains largely supportive. Improvement in the treatment of DMD will depend upon the development of better therapies. Affected boys become symptomatic at 3 to 5 years of age with proximal leg weakness that impairs mobility, ability to get up from a squat, and precludes a normal ability to run. By 8 years of age, some affected boys begin to lose the ability to walk and resort to a wheelchair for mobility. This shift from the ambulant to non-ambulant phase occurs in all boys with a diagnosis of DMD by age 12 years. In this study, participants will be randomized into groups after being screened to determine eligibility. Participants will then be followed for a 12-month investigation period.

Official Title
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PITT0503: Clinical Trial of Coenzyme Q10 and Prednisone in Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Prednisone
* Dietary Supplement: Coenzyme Q10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10-18 years Non-ambulatory (primary mode of transportation is via wheelchair for 3 years or less) Confirmed DMD diagnosis Steroid-naive for the 6 months prior to screening Stable dose of b-blocker or ACE inhibitor medication for the 6 months prior to screening, if taking either of these medications Ability to provide reproducible repeat QMT grip score within 15% of first assessment score Has not participated in other therapeutic research protocol within the last 6 months prior to screening Ability to swallow tablets Exclusion Criteria: Failure to achieve one or more of the diagnostic inclusion criteria cited above Symptomatic DMD carrier Use of carnitine, other amino acids, creatine, glutamine, CoQ10 or any herbal medicines (this would not include herbal teas unless they are consumed daily with intended medicinal effect) within the last 3 months History of significant concomitant illness or significant impairment of renal or hepatic function, or other contraindication to steroid therapy Positive PPD No prior exposure to chickenpox and no immunization against chicken pox Baseline serum CoQ10 level of 5.0mg/ml or greater

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>CoenzymeQ10 taken once a day each morning by mouth. | Dietary Supplement: Coenzyme Q10<br>* serum levels of greater or equal to 2.5 micrograms/mL.<br>* Other names: CoQ10;|
| Active Comparator: 2<br>Prednisone taken once a day each morning by mouth | Drug: Prednisone<br>* Prednisone 0/75 mg/kg/day.<br>|
| Active Comparator: 3<br>CoenzymeQ10 and prednisone each taken once a day in the morning by mouth. | Drug: Prednisone<br>* Prednisone 0/75 mg/kg/day.<br>Dietary Supplement: Coenzyme Q10<br>* serum levels of greater or equal to 2.5 micrograms/mL.<br>* Other names: CoQ10;|
| No Intervention: 4<br>Enhanced standard of care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One Year Change of Left Ventricular Mean Systolic Wall Stress/Rate-corrected Velocity of Fiber Shortening Relation. | Comparing change from baseline of mean systolic wall stress and rate-corrected mean velocity of circumferential shortening in the three treatment groups relative to the enhanced standard of care group and relative to each other at one year. The values are obtained via an echocardiogram read locally at each site. | 12 months | 
| One Year Change in Pulmonary Function (Forced Expiratory Volume, FEV1 and Forced Vital Capacity, FVC) | Comparing change from baseline levels in pulmonary function (FEV1 and FVC) in the three treatment groups relative to the enhanced standard of care group and relative to each other at one year. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare Side Effect Profiles of the Three Study Groups | To compare side effect profiles of the three regimens to the enhanced standard of care group, to include height, weight, weight/height ratio, body mass index, cataract formation, blood glucose, blood pressure, and behavioral changes. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscular dystrophy, Duchenne, CoQ10, prednisone