The Myelin Disorders Biorepository Project (MDBP)
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|ClinicalTrials.gov Identifier: NCT03047369|
Recruitment Status : Recruiting
First Posted : February 9, 2017
Last Update Posted : December 22, 2021
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.
|Condition or disease|
|Leukodystrophy White Matter Disease Leukoencephalopathies Aicardi Goutieres Syndrome Metachromatic Leukodystrophy TUBB4A-Related Leukodystrophy 4H Syndrome Krabbe Disease Alexander Disease Pelizaeus-Merzbacher Disease Adrenoleukodystrophy Adrenomyeloneuropathy Multiple Sulfatase Deficiency Megalencephalic Leukoencephalopathy With Subcortical Cysts Vanishing White Matter Disease Cockayne Syndrome Labrune Syndrome ADLD Gangliosidoses Peroxisomal Biogenesis Disorder Adult-Onset Leukodystrophy With Neuroaxonal Spheroids Hereditary Diffuse Leukoencephalopathy With Spheroids|
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.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||12000 participants|
|Target Follow-Up Duration:||10 Years|
|Official Title:||The Myelin Disorders Biorepository Project and Global Leukodystrophy Initiative Clinical Trials Network|
|Actual Study Start Date :||December 8, 2016|
|Estimated Primary Completion Date :||December 8, 2026|
|Estimated Study Completion Date :||December 8, 2026|
- Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy [ Time Frame: 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.
- Assess Validity of Next-Generation Sequencing in the Diagnosis of Leukodystrophies [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 01/08/2016 - 01/08/2026 ]Includes a longitudinal collection of clinical data on diagnostic and therapeutic interventions in leukodystrophy patients and related controls.
- Track Natural History of Leukodystrophy Patients [ Time Frame: 01/08/2016 - 01/08/2026 ]Includes longitudinal collection of clinical data on disease presentation, progression and morbidities.
- Establish Disease Mechanisms in Leukodystrophies [ Time Frame: 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 [ Time Frame: 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.
Biospecimen Retention: Samples With DNA
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): NCT03047369
|Contact: Omar S. Sherbini, MPHfirstname.lastname@example.org|
|United States, California|
|Stanford University (Lucile Packard Children's Hospital)||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Swata Patnaik, MA 650-721-1458 email@example.com|
|Contact: Jenny Winterbottom, BA 650-740-0186 firstname.lastname@example.org|
|Principal Investigator: Keith Van Haren, MD|
|Sub-Investigator: Maura Ruzhnikov, MD|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Nhu Chau, BS 202-476-6394 email@example.com|
|Contact: Julie Rhee, NP 202-476-2120 firstname.lastname@example.org|
|Principal Investigator: Jamie Fraser, MD, PhD|
|United States, Georgia|
|Emory University (Children's Healthcare of Atlanta)||Recruiting|
|Atlanta, Georgia, United States, 30342|
|Contact: Meena Verma, MBBS, DCH 404-785-2994 email@example.com|
|Contact: Maria Cordero, BS 404-785-4597 firstname.lastname@example.org|
|Principal Investigator: Stephanie Keller, MD|
|United States, Maryland|
|Kennedy Krieger Institute||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Jordan Goodman, MS 443-923-2769 email@example.com|
|Principal Investigator: Ali Fatemi, MD, MBA|
|Sub-Investigator: Amena Smith Fine, MD, PhD|
|United States, Massachusetts|
|Massachusetts General Hospital (MGH)||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Haley Andonian, BS 617-724-1379 firstname.lastname@example.org|
|Contact: Claudia Brito Pires, BS 617-724-1330 email@example.com|
|Principal Investigator: Florian Eichler, MD|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Omar Sherbini, MPH 215-590-3068 firstname.lastname@example.org|
|Principal Investigator: Adeline Vanderver, MD|
|Sub-Investigator: Laura Adang, MD, PhD, MSTR|
|Sub-Investigator: Amy Waldman, MD, MSCE|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Chistine Mialki 215-898-8282 Christine.Mialki@pennmedicine.upenn.edu|
|Principal Investigator: Jennifer Orthmann-Murphy, MD, PhD|
|United States, Texas|
|Baylor College of Medicine (Texas Children's Hospital)||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Ivania Patry, MD 832-826-5961 email@example.com|
|Principal Investigator: Lisa Emrick, MD|
|United States, Utah|
|University of Utah (Primary Children's Hospital)||Recruiting|
|Salt Lake City, Utah, United States, 84112|
|Contact: Kelsee Parry, BS 801-690-2317 firstname.lastname@example.org|
|Contact: Tate Keough, AS 801-581-5522 email@example.com|
|Principal Investigator: Josh Bonkowsky, MD, PhD|
|Principal Investigator:||Adeline Vanderver, MD||Children's Hospital of Philadelphia|