We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01484678
Recruitment Status : Recruiting
First Posted : December 2, 2011
Last Update Posted : July 13, 2021
Sponsor:
Collaborators:
Oregon Health and Science University
Children's Hospital of Philadelphia
Shriners Hospitals for Children
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
University of Florida

Brief Summary:

The purpose of this research study is to determine the potential of magnetic resonance imaging, spectroscopy, and whole body imaging to monitor disease progression and to serve as an objective outcome measure for clinical trials in Muscular Dystrophy (MD).

The investigators will compare the muscles of ambulatory or non-ambulatory boys/men with DMD with muscles of healthy individuals of the same age and monitor disease progression in those with DMD over a 5-10 year period. The amount of muscle damage and fat that the investigators measure will also be related to performance in daily activities, such as walking and the loss of muscle strength. In a small group of subjects the investigators will also assess the effect of corticosteroid drugs on the muscle measurements.

Additionally, the investigators will map the progression of Becker MD following adults with this rare disease. The primary objective is to conduct a multi-centered study to validate the potential of non-invasive magnetic resonance imaging and magnetic resonance spectroscopy to monitor disease progression and to serve as a noninvasive surrogate outcome measure for clinical trials in DMD and BMD. The secondary objective is to characterize the progressive involvement of the lower extremity, upper extremity, trunk/respiratory muscles in boys/men with DMD and BMD guiding clinical trials.


Condition or disease
Duchenne Muscular Dystrophy Becker Muscular Dystrophy

Detailed Description:
The overall objective of this proposal is to validate the potential of noninvasive magnetic resonance imaging (MRI) and spectroscopy (MRS) to monitor disease progression and to serve as an outcome measure for clinical trials in muscular dystrophies. Duchenne muscular dystrophy (DMD) is one of the most devastating genetically linked neuromuscular diseases and is characterized by the absence of dystrophin, resulting in progressive muscle weakness, loss of walking ability and premature death. Despite the poor prognosis therapeutic interventions have been lacking, and outcome measures for clinical trials have been limited to measures of muscle function, quality of life, serum biomarkers of muscle breakdown and invasive muscle biopsies. Closely related to DMD, Becker muscular dystrophy (BMD) has also been largely neglected in therapeutic development, due to its heterogeneity, small patient population, lack of outcome measures and uncertainty surrounding the patterns of disease progression, which may be mutation-dependent. Additional quantitative outcome measures that are noninvasive and sensitive to changes in muscle structure and composition are needed to facilitate the rapid translation of promising new interventions from preclinical studies to clinical trials in both forms of muscular dystrophy. As such, this project targets the development and validation of magnetic resonance as a noninvasive biomarker of disease progression in muscular dystrophy. Using a multi-site research design this study will characterize the intramuscular lipid content, cellular muscle damage and contractile area in the lower and/or upper extremity muscles of 200 ambulatory or non-ambulatory boys/men with DMD, 105 ambulatory or non-ambulatory men with BMD, and 110 healthy age matched boys/men using a combination of sophisticated MRI and MRS technologies. The trunk and respiratory muscles will be characterized in a subgroup of subjects (80 DMD, 20 BMD and 10 controls). In order to assess the sensitivity of each MR measure individually as well as composite MR measures (combination of muscles) to disease progression, all boys/men with DMD or BMD will be re-evaluated in yearly or 6 month intervals. The predictive outcome value of MRI/MRS will be further evaluated by determining the relationship between changes in MR measures and loss in muscle strength and/or functional ability. Using MRI/MRS we will also examine the effect of initiating corticosteroid treatment on skeletal muscle characteristics and composition. Examination of muscles in BMD patients will allow us to increase our understanding of how much dystrophin is needed to protect the muscle. To this end we will specifically examine the relationship between the MR phenotype (e.g. fast or slow increases in fat fraction) and dystrophin mutations, dystrophin expression and other histological markers. Finally, to ensure the rigor of this study we will examine the day-day reproducibility, inter MR system reproducibility and inter-validate the MR measures using localized MRS (golden standard). We anticipate that the MR techniques developed and validated in this study will be suitable for clinical trials in a wide range of muscular dystrophies and other neuromuscular diseases. In addition, MR characterization may serve as a powerful tool to further advance our understanding of the pathogenesis of muscular dystrophy and help guide the design of future trials.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 550 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : August 2025


Group/Cohort
Age Matched Controls

Age matched non-affected (non-DMD) boys * This arm is full

Age matched non-affected men, matched for men with Becker MD *Recruiting

Boys/Men with DMD
This group will include ambulatory and non-ambulatory boys/men with Duchenne Muscular Dystrophy ranging from 5-30 years old. *Recruiting
Adults with Becker MD
This group will include ambulatory and non-ambulatory men with Becker Muscular Dystrophy ranging from 18-62 years old. * Recruiting



Primary Outcome Measures :
  1. Change from baseline in intramuscular lipid up to 3-10 years [ Time Frame: Change in baseline up to 3-10 years ]

    In BMD and DMD, the from baseline in intramuscular lipid of upper/ lower extremity and trunk/respiratory muscles, as well as composite measures.

    MR measures of intramuscular lipid will be measured in yearly intervals for a period up to 3-10 years.


  2. Change from baseline in muscle T2 up to 3 months in DMD [ Time Frame: Change in baseline up to 3 months ]
    In a subgroup of subjects the effect of corticosteroids on muscle T2 will be measured at 3 and 6 months. Muscle T2 is a noninvasive marker of muscle damage/inflammation and will be measured using MR. This substudy requires its own Primary and Secondary Outcome measures.

  3. Correlation between MR measures of intramuscular lipid, functional endpoints and histological markers. [ Time Frame: Through study completion, an average of 1 year ]
    In both BMD and DMD, the correlation between MR measures and functional endpoints will be determined, as well as the ability of MR measures to predict future change and loss in function.


Secondary Outcome Measures :
  1. Change from baseline in muscle T2 up to 5-10 years [ Time Frame: Change in baseline up to 5-10 years ]

    Muscle T2 will be measured in the lower extremity and/or upper extremity muscles using MR at yearly intervals up to 5-10 years.

    We will report the change for each year interval.


  2. Change from baseline in muscle contractile area up to 5-10 years [ Time Frame: change in baseline up to 5-10 years ]
    Muscle contractile area will be measured in the lower extremity and/or upper extremity muscles using MR at yearly intervals up to 5 years. We will report the change for each year interval.

  3. Change from baseline in muscle T2 at 6 months [ Time Frame: Change in baseline up to 6 months ]
    In a subgroup of subjects the effect of corticosteroids on muscle T2 will be measured at 3 and 6 months. Muscle T2 is a noninvasive marker of muscle damage/inflammation and will be measured using MR. This substudy requires its own Primary and Secondary Outcome measures.


Biospecimen Retention:   Samples With DNA
Blood, Urine, Saliva samples collected, and a one time Muscle Biopsy in Becker MD subjects and matched controls only


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   5 Years to 62 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects are recruited from across the country. Investigators have a website (www.imagingNMD.org) and advertise the study nationally through list serves. The study will be advertised at the website of non-profit MD organizations. General information will be emailed to faculty and colleagues around the country. Fliers and brochures will be distributed in participating local clinics, MDA clinics, non-profit organizations, local neuromuscular clinics, and in strategic locations in associated hospitals. Age-matched healthy men will be recruited to match subjects with Becker MD from local and university communities. Individuals interested in this study are asked to contact the site clinical coordinator, who will complete a telephone screening interview to assess eligibility.
Criteria

Inclusion Criteria for boys with DMD:

1. Ambulatory and non-ambulatory males (ages 5-30 at baseline testing) previously diagnosed with DMD based on:

  • clinical features with onset of symptoms before age five
  • elevated serum creatine kinase level or
  • absence of dystrophin expression, as determined by immunostain or western blot (<2%) and/or DNA confirmation of a dystrophin mutation *Subjects will not be excluded based on corticosteroid treatment or other clinical trials

Inclusion Criteria for adults with Becker MD:

  1. Ambulatory males (ages 18-62) without disease or injury to the lower extremities
  2. Specific recruitment of a subset of individuals with deletion mutations in the dystrophin gene involving either exon 51 or exon 45.

Inclusion Criteria for age matched controls for Becker MD subjects:

1. Ambulatory males (ages 18-62) without disease or injury to the lower and/or upper extremities will be eligible to participate in this study

Exclusion Criteria:

  1. Males with a contraindication to an MR examination
  2. Males with unstable medical problems
  3. Males who are not able to cooperate during testing
  4. Males with a secondary condition that may impact muscle metabolism, muscle function or functional ability (i.e. cerebral palsy, endocrine disorders, mitochondrial disease)
  5. Daytime ventilation
  6. Implantable Cardioverter Defibrillator- (ICD) or pace maker
  7. Healthy boys/men who participate in competitive sports specific training in excess of 8 hours per week

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): NCT01484678


Contacts
Layout table for location contacts
Contact: Krista Vandenborne, PhD 352-273-6100 kvandenb@phhp.ufl.edu
Contact: Claudia Senesac, PhD 352-273-6453 csenesac@phhp.ufl.edu

Locations
Layout table for location information
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Krista Vandenborne, PhD    352-273-6100    kvandenb@phhp.ufl.edu   
Contact: Claudia Senesac, PhD    352-273-6453    csenesac@phhp.ufl.edu   
Principal Investigator: Krista Vandenborne, PhD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: William Rooney, PhD    503-418-1532    rooneyw@ohsu.edu   
Contact: Laura McMahon    503-418-1540    mcmahola@ohsu.edu   
Principal Investigator: Bill Rooney, PhD         
United States, Pennsylvania
Children's Hospital of Philadelphia Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Florida
Oregon Health and Science University
Children's Hospital of Philadelphia
Shriners Hospitals for Children
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
Layout table for investigator information
Principal Investigator: William Rooney, PhD Oregan Health and Science University
Principal Investigator: H. Lee Sweeney, PhD University of Florida
Principal Investigator: Krista Vandenborne, PhD University of Florida
Additional Information:
Publications:

Layout table for additonal information
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01484678    
Other Study ID Numbers: IRB201700056-N
R01AR056973 ( U.S. NIH Grant/Contract )
176-2010 ( Other Identifier: Univeristy of Florida )
OCR16243 ( Other Identifier: University of Florida )
First Posted: December 2, 2011    Key Record Dates
Last Update Posted: July 13, 2021
Last Verified: July 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Florida:
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Magnetic Resonance Spectroscopy
Magnetic Resonance Imaging
Muscle
Additional relevant MeSH terms:
Layout table for 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