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

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

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Prednisone; Drug: Prednisone; Drug: Deflazacort

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: Interventional
• Enrollment (Actual): 196
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • Children's Hospital London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario (CHEO)
• Germany
  • Dresden, Germany, 01307
    • Children's Hospital, Technical University Dresden
  • Essen, Germany, 45122
    • University Hospital of Essen
  • Freiburg, Germany, 79110
    • University Medical Center Freiburg
  • Göttingen, Germany, 37075
    • Children's University Hospital, Göttingen
• Italy
  • Messina, Italy, 98125
    • University of Messina AOU Policlinico Gaetano Martino
  • Milan, Italy, 20133
    • C. Besta Neurological Institute Foundation
  • Padova, Italy, 35128
    • University of Padova School of Medicine
  • Torino, Italy, 10126
    • Neuromuscular Center University of Turin
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Heart of England NHS Foundation Trust Birmingham Heartland's Hospital
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's Hospital NHS Trust
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children NHS Trust
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
  • Newcastle Upon Tyne, United Kingdom, NE1 3BZ
    • Institute of Human Genetics, International Centre for Life
  • England
    • Leeds, England, United Kingdom, LS2 9NS
      • The General Infirmary at Leeds
  • Scotland
    • Glasgow, Scotland, United Kingdom, G3 8SJ
      • Greater Glasgow and Clyde NHS Yorkhill Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA) Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Science Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Newcastle University; University Medical Center Freiburg
• Investigators: Principal Investigator: Robert C. Griggs, MD, University of Rochester; Principal Investigator: Kate Bushby, MD, Newcastle University

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): November 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 23, 2012

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: multi-center; muscular dystrophy; prednisone; neuromuscular disease; deflazacort
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Deflazacort
• Other Study ID Numbers: U01NS061799 (U.S. NIH Grant/Contract); 2010-023744-33 (EudraCT Number); 46102316 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No