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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: Prednisone Drug: Deflazacort Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 196 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Duchenne Muscular Dystrophy: Double-blind Randomized Trial to Find Optimum Steroid Regimen
Study Start Date : January 2013
Actual Primary Completion Date : November 2019
Actual Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
Experimental: Intermittent prednisone
intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off)
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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

  3. 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.


Secondary Outcome Measures :
  1. 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.


  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Heart Rate [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.

  7. 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.

  8. 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.

  9. Left Ventricular Ejection Fraction Percent [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.

  10. Fractional Shortening Percent [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.

  11. PR Interval [ Time Frame: 36 months ]
    Measured by trans-thoracic echocardiogram and 12-lead ECG.

  12. Participant Weight [ Time Frame: 36 months ]
  13. Participant Height [ Time Frame: 36 months ]
  14. Participant Body Mass Index [ Time Frame: 36 months ]

Eligibility Criteria
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Ages Eligible for Study:   4 Years to 7 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01603407


Locations
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Sponsors and Collaborators
University of Rochester
Newcastle University
University Medical Center Freiburg
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Robert C. Griggs, MD University of Rochester
Principal Investigator: Kate Bushby, MD Newcastle University
  Study Documents (Full-Text)

Documents provided by Robert Griggs, MD, University of Rochester:
Study Protocol  [PDF] December 18, 2019
Statistical Analysis Plan  [PDF] February 16, 2021

More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Guglieri M, Bushby K, McDermott MP, Hart KA, Tawil R, Martens WB, Herr BE, McColl E, Speed C, Wilkinson J, Kirschner J, King WM, Eagle M, Brown MW, Willis T, Griggs RC; FOR-DMD Investigators of the Muscle Study Group; Straub V, van Ruiten H, Childs AM, Ciafaloni E, Shieh PB, Spinty S, Maggi L, Baranello G, Butterfield RJ, Horrocks IA, Roper H, Alhaswani Z, Flanigan KM, Kuntz NL, Manzur A, Darras BT, Kang PB, Morrison L, Krzesniak-Swinarska M, Mah JK, Mongini TE, Ricci F, von der Hagen M, Finkel RS, O'Reardon K, Wicklund M, Kumar A, McDonald CM, Han JJ, Joyce N, Henricson EK, Schara-Schmidt U, Gangfuss A, Wilichowski E, Barohn RJ, Statland JM, Campbell C, Vita G, Vita GL, Howard JF Jr, Hughes I, McMillan HJ, Pegoraro E, Bello L, Burnette WB, Thangarajh M, Chang T. Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA. 2022 Apr 19;327(15):1456-1468. doi: 10.1001/jama.2022.4315.

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Responsible Party: Robert Griggs, MD, Professor of Neurology, University of Rochester
ClinicalTrials.gov Identifier: NCT01603407    
Other Study ID Numbers: U01NS061799 ( U.S. NIH Grant/Contract )
2010-023744-33 ( EudraCT Number )
U01NS061799 ( U.S. NIH Grant/Contract )
46102316 ( Registry Identifier: ISRCTN )
First Posted: May 23, 2012    Key Record Dates
Results First Posted: August 12, 2022
Last Update Posted: August 12, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Robert Griggs, MD, University of Rochester:
prednisone
deflazacort
muscular dystrophy
neuromuscular disease
multi-center
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Prednisone
 Deflazacort
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors