Finding the Optimum Regimen for Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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The Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR DMD) study will compare three ways of giving corticosteroids to boys with Duchenne muscular dystrophy (DMD) to determine which of the three ways increases muscle strength the most, and which causes the fewest side effects. Using the results of this study, the investigators aim to provide patients and families with clearer information about the best way to take these drugs.

Detailed Description
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Boys with Duchenne muscular dystrophy experience progressive muscle weakness as they grow up. Corticosteroids are currently the only medicine that has been shown to increase muscle strength in boys with DMD. Benefits include an increase in the length of time that boys could continue to walk, reduction in the development of curvature of the spine, a longer time of adequate breathing, and possible protection against the development of heart problems. Doctors have tried different ways of prescribing corticosteroids in order to decrease undesirable side effects of the drug. No controlled, long-term study has ever looked at the effects of different corticosteroids to see which one improves strength the most and which one causes the fewest side effects, over a period of time. Different doctors in different countries prescribe the drugs in different ways, and some do not prescribe corticosteroids at all. The FOR DMD study will enroll boys with DMD ages 4-7. The study will look at three ways of taking the following corticosteroids by the mouth to determine which increases muscle strength the most, and which causes the fewest side effects: Prednisone 0.75mg/kg/day Prednisone 0.75mg/kg/day switching between 10 days on and 10 days off treatment Deflazacort 0.9mg/kg/day. The study will take place at 40 academic medical centers in the United States, Canada, United Kingdom, Germany and Italy.

Official Title
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Duchenne Muscular Dystrophy: Double-blind Randomized Trial to Find Optimum Steroid Regimen

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Prednisone
* Drug: Prednisone
* Drug: Deflazacort


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of signed and dated informed consent form. Confirmed diagnosis of Duchenne muscular dystrophy Age greater than or equal to 4 years and less than 8 years old Ability to rise independently from floor, from supine to standing Willingness and ability to comply with scheduled visits, drug administration plan and study procedures Ability to maintain reproducible FVC measurements. Exclusion Criteria: History of major renal or hepatic impairment, immunosuppression or other contraindications to corticosteroid therapy. History of chronic systemic fungal or viral infections. Acute bacterial infection(including TB) would exclude from enrolment until the infection had been appropriately treated and resolved. Diabetes mellitus. Idiopathic hypercalcuria. Lack of chicken pox immunity and refusal to undergo immunization. Evidence of symptomatic cardiomyopathy at screening assessment (one to three months prior to the baseline visit). Asymptomatic cardiac abnormality on investigation would not be an exclusion. Current or previous treatment (greater than four consecutive weeks of oral therapy) with corticosteroids or other immunosuppressive treatments for DMD or other recurrent indications (e.g., asthma), unless approved by FOR-DMD Team (i.e., concurrent participation in another allowed DMD trial). Inability to take tablets, as assessed by the site investigator by the end of the screening period (the screening period ranges from one to three months prior to the baseline visit). Allergy/sensitivity to study drugs or their formulations including lactose and/or sucrose intolerance. Severe behavioral problems, including severe autism. Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow up will be correctly completed or impair the assessment of study results, in the judgment of the site investigator. Weight of less than 13 kilograms. Exposure to any investigational drug currently or within 3 months prior to start of study treatment.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 7 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily prednisone<br>daily prednisone (0.75 mg/kg/day) | Drug: Prednisone<br>* daily prednisone (0.75 mg/kg/day) tablets for 36-60 months<br>|
| Experimental: Intermittent prednisone<br>intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) | Drug: Prednisone<br>* intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) tablets for 36 to 60 months<br>|
| Experimental: Daily deflazacort<br>daily deflazacort (0.9 mg/kg/day | Drug: Deflazacort<br>* daily deflazacort (0.9 mg/kg/day) tablets for 36-60 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity | Forced vital capacity was measured during a spirometry test. Forced expiratory volume (FEV) measures how much air a person can exhale during a forced breath. Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test. | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 
| Rise From the Floor Velocity | Reciprocal of time to rise from the floor | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 
| Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction With Treatment Score | The TSQM Global Satisfaction with Treatment is a 14-item questionnaire that ranges from 0 - 100 with higher scores indicating better outcomes. | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| North Star Ambulatory Assessment (NSAA) Score | The North Star Ambulatory Assessment (NSAA) is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne Muscular Dystrophy (DMD). It is usually used to monitor the progression of the disease and treatment effects. The activities are graded as follows: 2 - Normal - no obvious modification of activity 1 - Modified method but achieves goal independent of physical assistance from another 0 - Unable to achieve independently This scale is ordinal with 34 as the maximum score indicating fully-independent function. | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 
| 6 Minute Walk Test | Measures the total distance walked in 6 minutes averaged over all post-baseline follow-up visits through Month 36. | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 
| Range of Motion (Goniometry) of Left Ankle | Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade averaged over all post-baseline visits. | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 
| Range of Motion (Goniometry) of Right Ankle | Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade averaged over all post-baseline visits. | Average of Months 3, 6, 12, 18, 24, 30 and 36 visits | 
| Number of Participants Who Tolerated the Regimen | The number of participants who completed 36 months of follow-up on the originally assigned dosage (for weight) of study medication. | 3 years | 
| Heart Rate | Measured by trans-thoracic echocardiogram and 12-lead ECG. | 36 months | 
| Quality of Life - Parent | Quality of life was measured by parent/guardian self-report for all children utilizing the PEDSQL measurement tool. This is a 23-question tool. Scores can range from 0 to 100, with higher scores indicating better quality of life for the child. | Average of Months 12, 24, and 36 visits | 
| Quality of Life- Child | Quality of life was measured by child self-report in children age 5 and older utilizing the PEDSQL measurement tool. This is a 23-question tool. Scores can range from 0 to 100, with higher scores indicating better quality of life. | Average of Months 12, 24, and 36 visits | 
| Left Ventricular Ejection Fraction Percent | Measured by trans-thoracic echocardiogram and 12-lead ECG. | 36 months | 
| Fractional Shortening Percent | Measured by trans-thoracic echocardiogram and 12-lead ECG. | 36 months | 
| PR Interval | Measured by trans-thoracic echocardiogram and 12-lead ECG. | 36 months | 
| Participant Weight |  | 36 months | 
| Participant Height |  | 36 months | 
| Participant Body Mass Index |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prednisone, deflazacort, muscular dystrophy, neuromuscular disease, multi-center