Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Florida
Sponsor:
Collaborators:
University of Pennsylvania
Oregon Health and Science University
Children's Hospital of Philadelphia
Shriners Hospitals for Children
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01484678
First received: October 10, 2011
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

The purpose of this research study is to determine the potential of magnetic resonance imaging to monitor disease progression and to serve as an objective outcome measure for clinical trials in Duchenne Muscular Dystrophy (DMD). The investigators also hope to learn more about the changes that occur in muscles of the lower leg in boys with DMD.

The investigators will compare the muscles of ambulatory boys with DMD with muscles of healthy children of the same age and monitor disease progression in boys with DMD over a 5 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.


Condition
Duchenne Muscular Dystrophy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Change from baseline in intramuscular lipid at 1 year [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    MR measures of intramuscular lipid will be measured in yearly intervals for a period up to 5 years.

  • Change from baseline in muscle T2 at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change from baseline in muscle T2 at 1 year [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

    Muscle T2 will be measured in the lower extremity muscles using MR at yearly intervals up to 5 years.

    We will report the change for each year interval.


  • Change from baseline in muscle contractile area at 1 year [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    Muscle contractile area will be measured in the lower extremity muscles using MR at yearly intervals up to 5 years. We will report the change for each year interval.

  • Change from baseline in muscle T2 at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 and Skin Samples Collected


Estimated Enrollment: 150
Study Start Date: May 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Age Matched Controls
Age matched non-affected (non-DMD) boys
Boys with DMD
This group will include ambulatory boys with Duchenne Muscular Dystrophy ranging form 5-14 years old.

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 Duchenne muscular dystrophy (DMD). 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 for patients with muscular dystrophy, therapeutic interventions have been lacking, and outcome measures for clinical trials have been limited to measures of muscle function, serum biomarkers of muscle breakdown and invasive muscle biopsies. 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. As such, this proposal 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 examine the intramuscular lipid content, muscle damage/inflammation and contractile area in the lower extremity muscles of 100 ambulatory boys with DMD and 50 healthy age matched boys using a combination of MRI and MRS technologies. In order to assess the sensitivity of each MR measure to disease progression, all boys with DMD will be reevaluated in yearly or 6 month intervals. In addition, the investigators will correlate changes in MR measures with standard measures of disease progression, such as loss in muscle strength and functional ability. Using MRI/MRS the investigators will also examine the effect of initiating corticosteroid treatment on skeletal muscle characteristics and composition. Finally, the investigators will deposit immortalized fibroblasts from carefully characterized DMD boys participating in this study in established tissue repositories.

The investigators anticipate that the MR techniques developed and validated in this proposal 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.

  Eligibility

Ages Eligible for Study:   5 Years to 14 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects will be recruited from across the country as well as locally. The investigators have established a website (www.imagingDMD.org) and advertise the study nationally through list serves.The study will also be advertised at the website of non-profit DMD 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, schools, and local pediatric clinics, and in strategic locations in associated hospitals. Age-matched healthy boys will be recruited from the families of the local DMD population as well as the university community. Parents of eligible subjects will be 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 males (ages 5-14) 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.
  2. Ability to ambulate independently for at least 100 meters without an external assistive device
  3. Ability to climb 4 stairs
  4. Subjects will not be excluded based on corticosteroid treatment

Inclusion Criteria for age matched controls:

1. Ambulatory males (ages 5-14) without disease or injury to the lower extremities

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. Healthy boys who participate in competitive sports specific training in excess of 8 hours per week. Participation in multiple recreational sports activities is not an exclusion.
  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: NCT01484678

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

Locations
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 Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Gihan Tennekoon, MD    215-590-1710    tennekoon@email.chop.edu   
Contact: Michele Toms    215-590-7727    toms@email.chop.edu   
Principal Investigator: Gihan Tennekoon, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lee Sweeney, PhD    215-898-8727    lsweeney@mail.med.upenn.edu   
Contact: Barbara Price    215-898-8725    priceb@mail.med.upenn.edu   
Principal Investigator: Lee Sweeney, PhD         
Sponsors and Collaborators
University of Florida
University of Pennsylvania
Oregon Health and Science University
Children's Hospital of Philadelphia
Shriners Hospitals for Children
Investigators
Principal Investigator: Gihan Tennekoon, MD Children's Hospital of Philadelphia
Principal Investigator: William Rooney, PhD Oregan Health and Science University
Principal Investigator: H. Lee Sweeney, PhD University of Pennsylvania
Principal Investigator: Krista Vandenborne, PhD University of Florida
  More Information

Additional Information:
Publications:
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01484678     History of Changes
Other Study ID Numbers: ImagingDMD, R01AR056973
Study First Received: October 10, 2011
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Duchenne Muscular Dystrophy
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Muscle

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on October 23, 2014