The Myelin Disorders Biorepository Project
- Conditions
- LeukodystrophyALDAicardi Goutieres SyndromeHBSLHBSL - Hypomyelination, Brain Stem, Spinal Cord, Leg SpasticityPLP1 Gene Duplication | Blood or Tissue | MutationsZellweger SyndromeRefsum DiseaseSjögrenGangliosidoses
- Registration Number
- NCT03047369
- Lead Sponsor
- Children's Hospital of Philadelphia
- Brief Summary
The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago.
Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.
- Detailed Description
Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of approximately 1:7000 live births. In the past, patients with white matter disease of unknown cause evaluated by the investigator achieved a diagnosis in fewer than 46% of cases after extensive conventional clinical testing. Even when a diagnosis is achieved, the diagnosis takes an average of eight years and this "odyssey" results in testing charges to patients and insurers in excess of $8,000 on average per patient, including patients who never achieve a diagnosis at all. With next generation approaches such as whole exome sequencing, the diagnostic efficacy is closer to 70%, but approximately a third of individuals do not achieve a specific etiologic diagnosis. These diagnostic challenges represent an urgent and unresolved gap in knowledge and disease characterization, as obtaining a definitive diagnosis is of paramount importance for leukodystrophy patients.
Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood, with little known about the best symptomatic management and, thus, limited standards of care are available for the management of these patients.
The purpose of this study is to: (Aim 1) Define novel homogeneous groups of patients with unclassified leukodystrophy and work toward finding the cause of these disorders; (Aim 2) assess the validity and utility of next-generation sequencing in the diagnosis of leukodystrophies; (Aim 3) establish disease mechanisms in selected known leukodystrophies; (Aim 4) track current care and natural history of these patients to define the longitudinal course and determinants of outcomes in these disorders; (Aim 5) contact subjects for future research studies and/or clinical programs.
This biorepository will use available basic science and clinical research approaches to establish novel diagnoses, biomarkers, and outcome measures for future clinical diagnostic and therapeutic approaches.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 12000
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy 01/08/2016 - 01/08/2026 In patients with an unclassified leukodystrophy, the study team will collect as much information as available from existing medical records including existing clinical evaluations, neuropsychological/rehabilitation evaluations, and results from blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. This data will be evaluated to create nosologic groups amongst patients with unclassified leukodystrophy. Additionally, this aim includes the collection and long-term banking of biological samples in subjects with classified and unclassified leukodystrophies to develop a biorepository. These samples will be compared to samples collected from control subjects, either collected directly from enrolled subjects or through existing banked biological samples.
- Secondary Outcome Measures
Name Time Method Track Natural History of Leukodystrophy Patients 01/08/2016 - 01/08/2026 Includes longitudinal collection of clinical data on disease presentation, progression and morbidities.
Assess Validity of Next-Generation Sequencing in the Diagnosis of Leukodystrophies 01/08/2016 - 01/08/2026 Unclassified leukodystrophy patients enrolled in this study may undergo next generation sequencing approaches, including research whole exome sequencing (WES), whole genome sequencing (WGS), RNA sequencing and high throughput genomics analysis in parallel to standard clinical testing to achieve novel molecular classifications.
Assess Utility of Next-Generation Sequencing in the Diagnosis of Leukodystrophies 01/08/2016 - 01/08/2026 Clinical utility defined as changes in care and clinical state, included changes in medical morbidities, surgeries, pharmacologic management of complications and implementation of disease specific therapies.
Track Current Care of Leukodystrophy Patients 01/08/2016 - 01/08/2026 Includes a longitudinal collection of clinical data on diagnostic and therapeutic interventions in leukodystrophy patients and related controls.
Establish Disease Mechanisms in Leukodystrophies 01/08/2016 - 01/08/2026 Specific leukodystrophies will be selected for further mechanistic study, using clinical and laboratory tools to establish increased understanding of the underlying pathophysiology. The over-riding hypothesis of this aim is that integrated biochemical, genomic, metabolic, histologic and immunologic profiles of patients with leukodystrophy will define downstream pathway changes consistent with primary defects causing white matter disease. Appropriate controls will be used for comparison to disease related samples.
Contact for Future Research Studies and/or Clinical Programs 01/08/2016 - 01/08/2026 Individuals enrolled in the study may be informed of other research studies, either at the Children's Hospital of Philadelphia or another site affiliated or not affiliated with this study, that may be of interest to them and/or their their families based on a specific diagnosis or lack thereof.
Trial Locations
- Locations (23)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
University of California, Davis (UC Davis Health)
🇺🇸Sacramento, California, United States
University of California, San Diego (Rady Children's Hospital)
🇺🇸San Diego, California, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Atrium Health Wake Forest Baptist
🇺🇸Winston-Salem, North Carolina, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
UT Health Houston
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Stanford University (Lucile Packard Children's Hospital)
🇺🇸Palo Alto, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Emory University (Children's Healthcare of Atlanta)
🇺🇸Atlanta, Georgia, United States
Kennedy Krieger Institute
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital (MGH)
🇺🇸Boston, Massachusetts, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Baylor College of Medicine (Texas Children's Hospital)
🇺🇸Houston, Texas, United States
University of Utah (Primary Children's Hospital)
🇺🇸Salt Lake City, Utah, United States