LeukodystrophyMDBPNCT03047369
The Myelin Disorders Biorepository Project
An observational study of Leukodystrophy and White Matter Disease, run by Children's Hospital of Philadelphia at 23 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukodystrophy, White Matter Disease, Leukoencephalopathies
- How many people
- 12,000 participants
- Where
- 23 sitesUnited States
- Study dates
- 8 Dec 2016to 8 Dec 2030
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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, or in the presence of variant(s) of uncertain significance or genotype consistent with leukodytrophy;
- 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.
- 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 (including affected patients' caregivers);
- Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent.
Who cannot join
- 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.
- Inability to provide consent.
Trial locations and contacts
23 sites in 1 country. Contact the study team or a site near you to ask about taking part.
23 sites in 1 country
United States23 sites, 23 recruiting
- Recruiting
Akron Children's Hospital
Akron, Ohio, 44308
Matthew Ginsberg, MD
- Recruiting
Emory University (Children's Healthcare of Atlanta)
Atlanta, Georgia, 30342
Stephanie Keller, MD
- Recruiting
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Ali Fatemi, MD, MBA
- Recruiting
Massachusetts General Hospital (MGH)
Boston, Massachusetts, 02114
Florian Eichler, MD
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Jennifer P Rubin, MD
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Margie Ream, MD, PhD
- Recruiting
Baylor College of Medicine (Texas Children's Hospital)
Houston, Texas, 77030
Lisa Emrick, MD
- Recruiting
UT Health Houston
Houston, Texas
Mary Kay Koenig, MD
- Recruiting
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Jonathan Santoro, MD
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55454
Paul Orchard, MD
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
Changrui Xiao, MD
- Recruiting
Stanford University (Lucile Packard Children's Hospital)
Palo Alto, California, 94304
Keith Van Haren, MD
- Recruiting
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Omar Sherbini, MPH, 215-590-3068, sherbinio@chop.edu
Adeline Vanderver, MD
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Jennifer Orthmann-Murphy, MD, PhD
- Recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15219
Deepa Rajan, MD
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Radhika Dhamija, MBBS
- Recruiting
University of California, Davis (UC Davis Health)
Sacramento, California, 95817
William Benko, MD
- Recruiting
University of Utah (Primary Children's Hospital)
Salt Lake City, Utah, 84112
Joshua Bonkowsky, MD, PhD
- Recruiting
University of California, San Diego (Rady Children's Hospital)
San Diego, California, 92123
Jennifer Yang, MD
- Recruiting
UCSF Benioff Children's Hospital
San Francisco, California, 94158
Alexander Fay, MD, PhD
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Emily Shelkowitz, MD
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Jamie Fraser, MD, PhD
- Recruiting
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
Jennifer Harmon, MD, PhD
About this study
Official title: The Myelin Disorders Biorepository Project and Global Leukodystrophy Initiative Clinical Trials Network
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.
Read the 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.
- Conditions
- Leukodystrophy, White Matter Disease, Leukoencephalopathies, 4H Syndrome, Adrenoleukodystrophy, AMN
- Keywords
- leukodystrophy, white matter disease, leukoencephalopathy, myelin, demyelinating, mdbp
- Medical subject headings
- Leukoencephalopathies, Attention Deficit Disorder with Hyperactivity, Adrenoleukodystrophy, Aicardi-Goutieres syndrome, Alexander Disease, Alexanders leukodystrophy, Canavan Disease, Xanthomatosis, Cerebrotendinous
What is being measured
The primary outcome is the main question the study is designed to answer.
Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy
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.
Measured: 10 years from enrollment
Secondary outcomes (6)
Assess Validity of Next-Generation Sequencing in the Diagnosis of Leukodystrophies
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.
Measured: 10 years from enrollment
Assess Utility of Next-Generation Sequencing in the Diagnosis of Leukodystrophies
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.
Measured: 10 years from enrollment
Track Current Care of Leukodystrophy Patients
Includes a longitudinal collection of clinical data on diagnostic and therapeutic interventions in leukodystrophy patients and related controls.
Measured: 10 years from enrollment
Track Natural History of Leukodystrophy Patients
Includes longitudinal collection of clinical data on disease presentation, progression and morbidities.
Measured: 10 years from enrollment
Establish Disease Mechanisms in Leukodystrophies
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.
Measured: 10 years from enrollment
Contact for Future Research Studies and/or Clinical Programs
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.
Measured: 10 years from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start8 Dec 2016
- Primary completion8 Dec 2030 (estimated)
- Study completion8 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukodystrophyStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12,000 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), National Center for Advancing Translational Sciences (NCATS), Biogen, Eli Lilly and Company, Myrtelle Inc., Orchard Therapeutics Ltd., Passage Bio, Inc., Synaptix Biotherapeutics Ltd., Takeda, Boehringer Ingelheim, Ionis Pharmaceuticals, Inc., Sanofi Winthrop Industrie, Sana Biotechnology, Yaya Foundation for 4H Leukodystrophy, University of Pennsylvania, United MSD Foundation, Foundation to Fight H-ABC, Calliope Joy Foundation, Don't Forget Me Foundation
- Responsible party
- Principal investigator, Adeline Vanderver, MD, Children's Hospital of Philadelphia
- Investigators
- Adeline Vanderver, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03047369
- Sponsor's protocol ID
- 14-011236
- Other IDs
- U54NS115052, U01NS106845
- Acronym
- MDBP
- Status last verified
- Oct 2025
- First submitted
- 1 Feb 2017
- Last updated
- 23 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Adang LA, Schlotawa L, Groeschel S, Kehrer C, Harzer K, Staretz-Chacham O, Silva TO, Schwartz IVD, Gartner J, De Castro M, Costin C, Montgomery EF, Dierks T, Radhakrishnan K, Ahrens-Nicklas RC. Natural history of multiple sulfatase deficiency: Retrospective phenotyping and functional variant analysis to characterize an ultra-rare disease. J Inherit Metab Dis. 2020 Nov;43(6):1298-1309. doi: 10.1002/jimd.12298. Epub 2020 Aug 20.
PubMed 32749716
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Myelin Disorders Biorepository Project and Global Leukodystrophy Initiative Clinical Trials Network
- ClinicalTrials.gov ID
- NCT03047369
- Acronym / sponsor ID
- MDBP / 14-011236
- Conditions
- Leukodystrophy, White Matter Disease, Leukoencephalopathies, 4H Syndrome, Adrenoleukodystrophy, AMN
- Keywords
- leukodystrophy, white matter disease, leukoencephalopathy, myelin, demyelinating, mdbp
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 12,000 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS), National Center for Advancing Translational Sciences (NCATS), Biogen, Eli Lilly and Company, Myrtelle Inc., Orchard Therapeutics Ltd., Passage Bio, Inc., Synaptix Biotherapeutics Ltd., Takeda, Boehringer Ingelheim, Ionis Pharmaceuticals, Inc., Sanofi Winthrop Industrie, Sana Biotechnology, Yaya Foundation for 4H Leukodystrophy, University of Pennsylvania, United MSD Foundation, Foundation to Fight H-ABC, Calliope Joy Foundation, Don't Forget Me Foundation
- Study start
- 8 Dec 2016 (actual)
- Primary completion
- 8 Dec 2030 (estimated)
- Study completion
- 8 Dec 2030 (estimated)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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, or in the presence of variant(s) of uncertain significance or genotype consistent with leukodytrophy;
- 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.
- Male or female of any age;
Key exclusion criteria (3 listed)
- 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.
- Inability to provide consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy
Time frame: 10 years from enrollment
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.
6 secondary outcomes
Assess Validity of Next-Generation Sequencing in the Diagnosis of Leukodystrophies
Time frame: 10 years from enrollment
Assess Utility of Next-Generation Sequencing in the Diagnosis of Leukodystrophies
Time frame: 10 years from enrollment
Track Current Care of Leukodystrophy Patients
Time frame: 10 years from enrollment
Track Natural History of Leukodystrophy Patients
Time frame: 10 years from enrollment
Establish Disease Mechanisms in Leukodystrophies
Time frame: 10 years from enrollment
Contact for Future Research Studies and/or Clinical Programs
Time frame: 10 years from enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2025.
- Derived from this study: PubMed 32749716Adang LA, Schlotawa L, Groeschel S, Kehrer C, Harzer K, Staretz-Chacham O, Silva TO, Schwartz IVD, Gartner J, De Castro M, Costin C, Montgomery EF, Dierks T, Radhakrishnan K, Ahrens-Nicklas RC. Natural history of multiple sulfatase deficiency: Retrospective phenotyping and functional variant analysis to characterize an ultra-rare disease. J Inherit Metab Dis. 2020 Nov;43(6):1298-1309. doi: 10.1002/jimd.12298. Epub 2020 Aug 20.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Adeline Vanderver, MD principal investigator
Children's Hospital of Philadelphia
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leukodystrophy and White Matter Disease, run by Children's Hospital of Philadelphia at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Omar S. Sherbini, MPH (215-590-3068, sherbinio@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy (time frame: 10 years from enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03047369, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2025.