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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Rochester
Sponsor:
Collaborators:
Newcastle University
University Medical Center Freiburg
Information provided by (Responsible Party):
Robert Griggs, MD, University of Rochester
ClinicalTrials.gov Identifier:
NCT01603407
First received: April 3, 2012
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Duchenne Muscular Dystrophy
Drug: Prednisone
Drug: Deflazacort
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • 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):

    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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 300
Study Start Date: January 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   4 Years to 7 Years
Genders 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).
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01603407

Contacts
Contact: Kimberly Hart 585-275-3767 kim_hart@urmc.rochester.edu

  Show 40 Study Locations
Sponsors and Collaborators
University of Rochester
Newcastle University
University Medical Center Freiburg
Investigators
Principal Investigator: Robert C. Griggs, MD University of Rochester
Principal Investigator: Kate Bushby, MD Newcastle University
  More Information

Publications:

Responsible Party: Robert Griggs, MD, Professor of Neurology, University of Rochester
ClinicalTrials.gov Identifier: NCT01603407     History of Changes
Other Study ID Numbers: U01NS061799, 2010-023744-33, U01NS061799, 46102316
Study First Received: April 3, 2012
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Office for Radiation Protection
Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University of Rochester:
prednisone
deflazacort
muscular dystrophy
neuromuscular disease
multi-center

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Deflazacort
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014