Finding the Optimum Regimen for Duchenne Muscular Dystrophy
- Registration Number
- NCT01603407
- Lead Sponsor
- University of Rochester
- Brief Summary
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
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:
1. Prednisone 0.75mg/kg/day
2. Prednisone 0.75mg/kg/day switching between 10 days on and 10 days off treatment
3. 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 196
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Daily prednisone Prednisone daily prednisone (0.75 mg/kg/day) Intermittent prednisone Prednisone intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) Daily deflazacort Deflazacort daily deflazacort (0.9 mg/kg/day
- Primary Outcome Measures
Name Time Method Forced Vital Capacity Average of Months 3, 6, 12, 18, 24, 30 and 36 visits 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.
Rise From the Floor Velocity Average of Months 3, 6, 12, 18, 24, 30 and 36 visits Reciprocal of time to rise from the floor
Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction With Treatment Score Average of Months 3, 6, 12, 18, 24, 30 and 36 visits The TSQM Global Satisfaction with Treatment is a 14-item questionnaire that ranges from 0 - 100 with higher scores indicating better outcomes.
- Secondary Outcome Measures
Name Time Method Participant Height 36 months Range of Motion (Goniometry) of Left Ankle Average of Months 3, 6, 12, 18, 24, 30 and 36 visits Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade averaged over all post-baseline visits.
Range of Motion (Goniometry) of Right Ankle Average of Months 3, 6, 12, 18, 24, 30 and 36 visits Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade averaged over all post-baseline visits.
Number of Participants Who Tolerated the Regimen 3 years The number of participants who completed 36 months of follow-up on the originally assigned dosage (for weight) of study medication.
Heart Rate 36 months Measured by trans-thoracic echocardiogram and 12-lead ECG.
Quality of Life - Parent Average of Months 12, 24, and 36 visits 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.
Quality of Life- Child Average of Months 12, 24, and 36 visits 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.
North Star Ambulatory Assessment (NSAA) Score Average of Months 3, 6, 12, 18, 24, 30 and 36 visits 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.6 Minute Walk Test Average of Months 3, 6, 12, 18, 24, 30 and 36 visits Measures the total distance walked in 6 minutes averaged over all post-baseline follow-up visits through Month 36.
Left Ventricular Ejection Fraction Percent 36 months Measured by trans-thoracic echocardiogram and 12-lead ECG.
Fractional Shortening Percent 36 months Measured by trans-thoracic echocardiogram and 12-lead ECG.
PR Interval 36 months Measured by trans-thoracic echocardiogram and 12-lead ECG.
Participant Weight 36 months Participant Body Mass Index 36 months
Trial Locations
- Locations (32)
C. Besta Neurological Institute Foundation
🇮🇹Milan, Italy
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Great Ormond Street Hospital for Children NHS Trust
🇬🇧London, United Kingdom
Institute of Human Genetics, International Centre for Life
🇬🇧Newcastle Upon Tyne, United Kingdom
University Medical Center Freiburg
🇩🇪Freiburg, Germany
Heart of England NHS Foundation Trust Birmingham Heartland's Hospital
🇬🇧Birmingham, United Kingdom
University of California Los Angeles (UCLA) Medical Center
🇺🇸Los Angeles, California, United States
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Messina AOU Policlinico Gaetano Martino
🇮🇹Messina, Italy
Neuromuscular Center University of Turin
🇮🇹Torino, Italy
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
University of Utah Medical Center
🇺🇸Salt Lake City, Utah, United States
Children's University Hospital, Göttingen
🇩🇪Göttingen, Germany
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University Hospital of Essen
🇩🇪Essen, Germany
University of Padova School of Medicine
🇮🇹Padova, Italy
Children's Hospital, Technical University Dresden
🇩🇪Dresden, Germany
Greater Glasgow and Clyde NHS Yorkhill Hospital
🇬🇧Glasgow, Scotland, United Kingdom
The General Infirmary at Leeds
🇬🇧Leeds, England, United Kingdom
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital London Health Sciences Centre
🇨🇦London, Ontario, Canada
Children's Hospital of Eastern Ontario (CHEO)
🇨🇦Ottawa, Ontario, Canada
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Alder Hey Children's Hospital NHS Trust
🇬🇧Liverpool, United Kingdom
University of New Mexico Health Science Center
🇺🇸Albuquerque, New Mexico, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States