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 : April 5, 2019
This is an observational designed 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.
These objectives will be achieved by collecting, and subsequently analyzing, data and samples in a longitudinal fashion across leukodystrophies.
|Condition or disease|
|Leukodystrophy White Matter Disease Leukoencephalopathies|
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 the 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. This remaining group of patients (unclassified leukodystrophy) offers the opportunity to describe novel disorders and provide improved diagnostic tools. 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: many are systemic abnormalities that manifest only testing white matter. Finally, little is known about the best symptomatic management of the many leukodystrophies without an etiologic cure 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; and (Aim 4) track current care and natural history of these patients to define the longitudinal course and determinants of outcomes in these disorders.
It is hoped that the present study will help clarify the nosology of the leukodystrophies and significantly advance our understanding of the pathogenesis of these diseases, the best diagnostic testing tools, and the best symptomatic management of these conditions. Due to the breadth of this approach, and the rarity of these conditions, these approaches will be carried out at multiple clinical centers with specialized expertise in the leukodystrophies.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||12000 participants|
|Target Follow-Up Duration:||10 Years|
|Official Title:||New Diagnostic Approaches in Leukodystrophy: The Myelin Disorders Biorepository and Natural History Project|
|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.
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 Sherbini, MPH||(215) firstname.lastname@example.org|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Omar Sherbini, MPH 215-590-3068 email@example.com|
|Principal Investigator: Adeline Vanderver, MD|
|Principal Investigator:||Adeline Vanderver, MD||Children's Hospital of Philadelphia|