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Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR-DMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01603407
Recruitment Status : Completed
First Posted : May 23, 2012
Results First Posted : August 12, 2022
Last Update Posted : August 12, 2022
Sponsor:
Collaborators:
Newcastle University
University Medical Center Freiburg
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Robert Griggs, MD, University of Rochester

Tracking Information
First Submitted Date  ICMJE April 3, 2012
First Posted Date  ICMJE May 23, 2012
Results First Submitted Date  ICMJE May 12, 2022
Results First Posted Date  ICMJE August 12, 2022
Last Update Posted Date August 12, 2022
Study Start Date  ICMJE January 2013
Actual Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2022)
  • Forced Vital Capacity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 21, 2012)		 Three-dimensional (multivariate) outcome
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):
  1. time to stand from lying (log-transformed)
  2. forced vital capacity
  3. subject/parent global satisfaction with treatment, as measured by the Treatment Satisfaction Questionnaire for Medication
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2022)
  • North Star Ambulatory Assessment (NSAA) Score [ Time Frame: 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 [ Time Frame: 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.
  • Range of Motion (Goniometry) of Left Ankle [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.
  • Quality of Life - Parent [ Time Frame: 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 [ Time Frame: 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.
  • Left Ventricular Ejection Fraction Percent [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.
  • Fractional Shortening Percent [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.
  • PR Interval [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.
  • Participant Weight [ Time Frame: 36 months ]
  • Participant Height [ Time Frame: 36 months ]
  • Participant Body Mass Index [ Time Frame: 36 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2012)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Finding the Optimum Regimen for Duchenne Muscular Dystrophy
Official Title  ICMJE Duchenne Muscular Dystrophy: Double-blind Randomized Trial to Find Optimum Steroid Regimen
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE
  • Drug: Prednisone
    daily prednisone (0.75 mg/kg/day) tablets for 36-60 months
  • Drug: Prednisone
    intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) tablets for 36 to 60 months
  • Drug: Deflazacort
    daily deflazacort (0.9 mg/kg/day) tablets for 36-60 months
Study Arms  ICMJE
  • Experimental: Daily prednisone
    daily prednisone (0.75 mg/kg/day)
    Intervention: Drug: Prednisone
  • Experimental: Intermittent prednisone
    intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off)
    Intervention: Drug: Prednisone
  • Experimental: Daily deflazacort
    daily deflazacort (0.9 mg/kg/day
    Intervention: Drug: Deflazacort
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2017)		 196
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2012)		 300
Actual Study Completion Date  ICMJE November 2019
Actual Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 4 Years to 7 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01603407
Other Study ID Numbers  ICMJE U01NS061799( U.S. NIH Grant/Contract )
2010-023744-33 ( EudraCT Number )
U01NS061799 ( U.S. NIH Grant/Contract )
46102316 ( Registry Identifier: ISRCTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Robert Griggs, MD, University of Rochester
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Rochester
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Newcastle University
  • University Medical Center Freiburg
  • National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: Robert C. Griggs, MD University of Rochester
Principal Investigator: Kate Bushby, MD Newcastle University
PRS Account University of Rochester
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP