Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR-DMD)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Duchenne Muscular Dystrophy: Double-blind Randomized Trial to Find Optimum Steroid Regimen|
- Three-dimensional (multivariate) outcome [ Time Frame: See description below ] [ Designated as safety issue: No ]
Three-dimensional outcome consisting of the following three components (each averaged over the Month 3, Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36 visits):
- time to stand from lying (log-transformed)
- forced vital capacity
- subject/parent global satisfaction with treatment, as measured by the Treatment Satisfaction Questionnaire for Medication
- The North Star Ambulatory Assessment (NSAA) [ Time Frame: Once during screening period (1 to 3 months prior to baseline visit), then again at Baseline visit (Month 0), Month 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 ] [ Designated as safety issue: No ]17 Item timed function tests to evaluate the motor ability in ambulant children with DMD. Timed Function Test Grading to differentiate those subjects with similarly fast times who may achieve a ceiling time Total score = Sum of all graded items. Of primary interest will be the average value of these outcomes over all post-baseline visits over the three year follow-up period
- 6 minute walk test [ Time Frame: Once during screening period (1 to 3 months prior to baseline visit), then again at Baseline visit (Month 0), Month 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 ] [ Designated as safety issue: No ]Measures the total distance walked in 6 minutes and the number of falls averaged over all post-baseline follow-up visits
- Range of motion (goniometry) [ Time Frame: Once during screening period (1 to 3 months prior to baseline visit), then again at Baseline visit (Month 0), Month 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 ] [ Designated as safety issue: No ]Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade
- Regimen tolerance [ Time Frame: Month 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 ] [ Designated as safety issue: Yes ]Assess the ability to tolerate the starting regimen of corticosteroids, defined as completing 3-5 years of follow-up on study medication with no deviation from the initially prescribed dosage level (increases in dosage band to accommodate growth and weight gain are allowed)
- Adverse event profile [ Time Frame: Month 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 ] [ Designated as safety issue: Yes ]The occurrence and severity of the following predictable adverse events (i.e., known side effects of corticosteroids) will be recorded. Behavior problems, bone fractures, cataracts, cushingoid features, GI symptoms, hypertension, immune/adrenal suppression, slow growth (height restriction), skin changes, weight gain, diabetes
- Quality of life [ Time Frame: Baseline visit (Month 0), Month 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 ] [ Designated as safety issue: No ]
Measured by child self-report (only in children aged 5 years and over) and by proxy (parent(s)/guardian(s)) report for all children. Utilizing Generic Peds QoL (23 questions ) NMD Disease-specific module will be used (25 questions).
The average values of these outcomes over all post-baseline assessments during the three-year follow-up period will be of primary interest.
- Cardiac function Cardiac function [ Time Frame: One to three months prior to the baseline visit, then every two years to the age of 10 years, and annually thereafter or at the onset of cardiac signs and symptoms and the year 3 visit ] [ Designated as safety issue: Yes ]Monitored by trans-thoracic echocardiogram and 12-lead ECG. The findings will be categorized as: normal; abnormal but not clinically significant;abnormal and clinically significant. The earliest definite, echo detectable impairment of left ventricular function is defined as ejection fraction < 55% and/or fractional shortening < 28%.Monitorred 12-lead ECG. If echocardiogram shows any impaired left ventricular function or evidence of regional motion abnormalities (posterior wall), the interval between evaluations will be reduced and treatment will be initiated
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||August 2019|
|Estimated Primary Completion Date:||August 2019 (Final data collection date for primary outcome measure)|
Experimental: Daily prednisone
daily prednisone (0.75 mg/kg/day)
daily prednisone (0.75 mg/kg/day) tablets for 36-60 months
Experimental: Intermittent prednisone
intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off)
intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) tablets for 36 to 60 months
Experimental: Daily deflazacort
daily deflazacort (0.9 mg/kg/day
daily deflazacort (0.9 mg/kg/day) tablets for 36-60 months
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01603407
|Contact: Kimberly Hartemail@example.com|
Show 40 Study Locations
|Principal Investigator:||Robert C. Griggs, MD||University of Rochester|
|Principal Investigator:||Kate Bushby, MD||Newcastle University|