Finding the Optimum Regimen for Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

— FOR-DMD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01603407
• Other study ID #: U01NS061799
• Secondary ID: 2010-023744-33U0
• Status: Completed
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: November 2019

Study information

• Verified date: August 2022
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: November 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 7 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Prednisone
daily prednisone (0.75 mg/kg/day) tablets for 36-60 months
• Prednisone
intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) tablets for 36 to 60 months
• Deflazacort
daily deflazacort (0.9 mg/kg/day) tablets for 36-60 months

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Children's Hospital London Health Sciences Centre	London	Ontario
Canada	Children's Hospital of Eastern Ontario (CHEO)	Ottawa	Ontario
Germany	Children's Hospital, Technical University Dresden	Dresden
Germany	University Hospital of Essen	Essen
Germany	University Medical Center Freiburg	Freiburg
Germany	Children's University Hospital, Göttingen	Göttingen
Italy	University of Messina AOU Policlinico Gaetano Martino	Messina
Italy	C. Besta Neurological Institute Foundation	Milan
Italy	University of Padova School of Medicine	Padova
Italy	Neuromuscular Center University of Turin	Torino
United Kingdom	Heart of England NHS Foundation Trust Birmingham Heartland's Hospital	Birmingham
United Kingdom	Greater Glasgow and Clyde NHS Yorkhill Hospital	Glasgow	Scotland
United Kingdom	The General Infirmary at Leeds	Leeds	England
United Kingdom	Alder Hey Children's Hospital NHS Trust	Liverpool
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Institute of Human Genetics, International Centre for Life	Newcastle Upon Tyne
United States	University of New Mexico Health Science Center	Albuquerque	New Mexico
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California Los Angeles (UCLA) Medical Center	Los Angeles	California
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Nemours Children's Hospital	Orlando	Florida
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
University of Rochester	National Institute of Neurological Disorders and Stroke (NINDS), Newcastle University, University Medical Center Freiburg

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  United Kingdom, 

References & Publications (56)

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* Note: There are 56 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Heart Rate	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	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
Secondary	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
Secondary	Left Ventricular Ejection Fraction Percent	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	Fractional Shortening Percent	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	PR Interval	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	Participant Weight		36 months
Secondary	Participant Height		36 months
Secondary	Participant Body Mass Index		36 months