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Trial record 1 of 1 for:    TUBB4A-Related Leukodystrophy
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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
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Takeda Pharmaceutical Co. Limited
PMD Foundation
Foundation to Fight H-ABC
Pennsylvania Department of Health
Homology Medicines, Inc
Biogen
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Adeline Vanderver, MD, 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.


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

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 12000 participants
Observational Model: Cohort
Time Perspective: Prospective
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





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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
Samples may be collected from affected subjects, as well as healthy controls. Samples may include blood, skin punch biopsy, CSF, urine, etc.) collected either for research or in the context of clinical procedures.


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.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Affected subjects will have either a confirmed or suspected diagnosis of leukodystrophy, or a related heritable disorder affecting the white matter of the brain. Healthy controls must be individuals in whom no leukodystrophy or related disorder has been suspected or confirmed.
Criteria

Inclusion Criteria (Affected Subjects):

  • Male or female of any age;
  • Suspected or confirmed diagnosis of leukodystrophy or other disorder affecting the white matter of the brain based primarily on the finding of central nervous system neuroimaging consistent with this diagnosis or on an existing diagnosis of a leukodystrophy or genetic leukoencephalopathy as defined in existing classification systems;
  • Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent;
  • Willingness to provide clinical data, participate in standardized assessments, and/or provide biologic samples.

Exclusion Criteria (Affected Subjects)

  • Established diagnosis at the time of referral that is not consistent with a genetic disorder of the white matter, such as an acquired demyelinating condition (e.g. multiple sclerosis), or an infectious etiology, with the exception of sequelae of congenital infections such as CMV;
  • Inability to provide consent.

Inclusion Criteria (Healthy Controls)

  • Male or female of any age;
  • Individuals with no confirmed or suspected diagnosis of leukodystrophy or other disorder affecting the white matter of the brain;
  • Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent.

Exclusion Criteria (Healthy Controls)

- Inability to provide consent.


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): NCT03047369


Contacts
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Contact: Omar S. Sherbini, MPH 215-590-3068 sherbinio@chop.edu

Locations
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United States, California
Stanford University (Lucile Packard Children's Hospital) Recruiting
Palo Alto, California, United States, 94304
Contact: Swata Patnaik, MA    650-721-1458    sweta@stanford.edu   
Contact: Jenny Winterbottom, BA    650-740-0186    jwinter2@stanford.edu   
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    nchau@childrensnational.org   
Contact: Julie Rhee, NP    202-476-2120    jurhee@childrensnational.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    meena.verma@choa.org   
Contact: Maria Cordero, BS    404-785-4597    maria.cordero@choa.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    goodmanj@kennedykrieger.org   
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    handonian@partners.org   
Contact: Claudia Brito Pires, BS    617-724-1330    cbritopires@partners.org   
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    sherbinio@chop.edu   
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    ivania.patry@bcm.edu   
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    kelsee.parry@hsc.utah.edu   
Contact: Tate Keough, AS    801-581-5522    tate.keough@hsc.utah.edu   
Principal Investigator: Josh Bonkowsky, MD, PhD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
National Institutes of Health (NIH)
Takeda Pharmaceutical Co. Limited
PMD Foundation
Foundation to Fight H-ABC
Pennsylvania Department of Health
Homology Medicines, Inc
Biogen
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Adeline Vanderver, MD Children's Hospital of Philadelphia
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Adeline Vanderver, MD, Program Director, Leukodystrophy Center, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT03047369    
Other Study ID Numbers: 14-011236
U54NS115052 ( U.S. NIH Grant/Contract )
U01NS106845 ( U.S. NIH Grant/Contract )
First Posted: February 9, 2017    Key Record Dates
Last Update Posted: December 22, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will be made available to researchers, sponsors, and other stakeholders. Data Use Agreement (DUA) must be put in place with any recipient of IPD. Only aggregate data will be shared publicly.
Time Frame: IPD may be shared at any time.
Access Criteria: Only aggregate data will be shared publicly. Please contact a member of the central study team for information regarding the release of IPD.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adeline Vanderver, MD, Children's Hospital of Philadelphia:
leukodystrophy
white matter disease
leukoencephalopathy
myelin
demyelinating
mdbp
Additional relevant MeSH terms:
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Leukodystrophy, Metachromatic
Leukodystrophy, Globoid Cell
Cockayne Syndrome
Adrenoleukodystrophy
Leukoencephalopathies
Gangliosidoses
Pelizaeus-Merzbacher Disease
Alexander Disease
Multiple Sulfatase Deficiency Disease
Peroxisomal Disorders
Syndrome
Disease
Pathologic Processes
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
Demyelinating Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Insufficiency