Duchenne Muscular Dystrophy
Conditions
Keywords
Muscular dystrophy, Duchenne, CoQ10, prednisone
Brief summary
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
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.
Interventions
DRUGPrednisone
Prednisone 0/75 mg/kg/day.
DIETARY_SUPPLEMENTCoenzyme Q10
serum levels of greater or equal to 2.5 micrograms/mL.
Sponsors
United States Department of Defense
Cooperative International Neuromuscular Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
10 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One Year Change of Left Ventricular Mean Systolic Wall Stress/Rate-corrected Velocity of Fiber Shortening Relation. | 12 months | 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. |
| One Year Change in Pulmonary Function (Forced Expiratory Volume, FEV1 and Forced Vital Capacity, FVC) | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare Side Effect Profiles of the Three Study Groups | 12 months | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment started in April 2007 at two participating centers of the Cooperative International Neuromuscular Research Group (CINRG): University of Pittsburgh and University of Puerto Rico. Enrollment closed in December 2008 by the CINRG Data and Safety Monitoring Board (DSMB) due to changes in standard of care.
Participants by arm
| Arm | Count |
|---|---|
| Coenzyme Q10 Alone CoenzymeQ10 taken once a day each morning by mouth.
Coenzyme Q10 : serum levels of greater or equal to 2.5 micrograms/mL. | 0 |
| Prednisone Alone Prednisone taken once a day each morning by mouth
Prednisone : Prednisone 0/75 mg/kg/day. | 0 |
| Coenzyme Q10 and Prednisone CoenzymeQ10 and prednisone each taken once a day in the morning by mouth.
Coenzyme Q10 : serum levels of greater or equal to 2.5 micrograms/mL.
Prednisone : Prednisone 0/75 mg/kg/day. | 1 |
| Enhanced Standard of Care Enhanced standard of care. | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol closure | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Coenzyme Q10 and Prednisone | Enhanced Standard of Care | Total |
|---|---|---|---|
| Age, Customized 10-18 years | 1 participants | 2 participants | 3 participants |
| Gender Female | 0 participants | 0 participants | 0 participants |
| Gender Male | 1 participants | 2 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 1 / 1 | 1 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 2 |
Outcome results
Primary
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.
Time frame: 12 months
Population: No analysis was performed as only 1 out of 3 participants completed all the pulmonary function measurements before the protocol was closed.
Primary
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.
Time frame: 12 months
Population: No analysis was performed as only 1 out of 3 participants completed all echocardiogram measurements before the protocol was closed.
Secondary
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.
Time frame: 12 months
Population: No analysis was performed as the study was closed with N=3 out of 120 and side effects profile between groups could not be analyzed.