LeukodystrophyNCT00889174
The Nosology and Etiology of Leukodystrophies of Unknown Causes
An observational study of Leukodystrophy and Leukoencephalopathy, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Background: A leukodystrophy is a disease affecting the white matter of the brain. The white matter conducts electricity from one part of the brain to the other. If the insulation, or myelin, is damaged, the brain s electrical pathways will not work properly. Read more about this study
- Who is it for?
- Ages 1 month to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Leukodystrophy, Leukoencephalopathy
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2009to 1 Aug 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 1 month to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients with white matter disease that is unclassified or of unknown cause, including, but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination and leukoencephalopathies with brainstem involvement.
- Parents or siblings of these subjects
Who cannot join
- Patients meeting above criteria but too ill to travel to the clinical center. In that case, consideration will be given to enrolling them for the collection of medical records and samples only.
- Patients meeting above criteria, but where the leukoencephalopathy is felt to be secondary to an acquired cause, for example traumatic or infectious.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Leukodystrophies of Unknown Cause
Background:
- A leukodystrophy is a disease affecting the white matter of the brain. The white matter conducts electricity from one part of the brain to the other. If the insulation, or myelin, is damaged, the brain s electrical pathways will not work properly. Researchers are trying to identify what causes leukodystrophy.
Read more
Objectives:
- To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genetic studies, and neurophysiologic and neuroimaging studies in patients with unclassified leukodystrophies to comprehensively characterize such patients and obtain comparative clinical profiles.
- To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genomic and proteomic tissue, and neurophysiologic and neuroimaging studies in patients with known leukodystrophies to investigate the underlying pathogenesis of these disorders.
- To better understand leukodystrophies of unknown cause and to identify the part of the DNA of the patient with leukodystrophy that is causing the problem.
Eligibility:
- Any individual with a known or suspected leukodystrophy is eligible to participate in this protocol, including
- Patients with white matter disease that is unclassified or of unknown cause, including but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination, and leukoencephalopathies with brainstem involvement.
- Parents or siblings of these subjects.
- Exclusion criteria include patients too ill to travel to the Clinical Center and patients for whom the leukoencephalopathy is felt to be secondary to an acquired cause (for example, traumatic or infectious).
Design:
- Patients will be seen either as an inpatient or outpatient depending on the tests that are planned. Patients may need to stay at the Clinical Center for 3 to 5 days.
- The following tests will be conducted as part of standard clinical care:
- Physical and neurological examinations, including blood and urine tests.
- Magnetic resonance based studies to produce a picture of the patient s brain (under general anesthesia).
- Spinal tap to measure chemicals in the spinal fluid (under general anesthesia in young children).
- Nerve biopsy, if the peripheral nerves are affected, or muscle biopsy, if the cells called the mitochondria or the muscles are involved (both under general anesthesia).
- The following studies may be performed as part of participation in the research:
- Blood, urine, spinal fluid, or muscle to understand the proteins, DNA, and molecules in these tissues.
- Skin biopsy to grow (in culture) skin cells and to analyze the skin microscopically.
- DNA studies to find new genes responsible for leukodystrophies and to better understand these diseases.
- Participation should be based on an interest to help further the research on leukodystrophies. Specific information about a patient s present or future health risks may not be gained.
Read the detailed description
Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of 1:5000 live births. As many as 50% of patients with white matter disease remain undiagnosed after conventional neuroimaging, biochemical and genetic testing, and therefore have unclassified leukodystrophies. Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood: many are systemic abnormalities that manifest only in white matter. The purpose of this study is to: (a) define novel homogeneous groups of patients with leukodystrophy and work toward finding the cause of these disorders and (b) establish disease mechanisms in selected classified leukodystrophies. In order to achieve these goals, patients with leukodystrophy will be analyzed by clinical, neurophysiological, biochemical and genetic means. For goal (a), patients would have been diagnosed as having an unclassified leukodystrophy or no known cause of their leukodystrophy at outside centers. At the Clinical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. For goal (b), selected leukodystrophies with a defined genetic cause will be selected for further mechanistic study, using clinical and laboratory tools to establish increased understanding of the underlying pathophysiology. 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.
- Conditions
- Leukodystrophy, Leukoencephalopathy
- Keywords
- Genetic Disorders of the White Matter, Leukodystrophies, Myelin, White Matter Disorder, Genetic Disorder
- Medical subject headings
- Leukoencephalopathies, Genetic Diseases, Inborn
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2009 (estimated)
- Study start24 Apr 2009
- Study completion1 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LeukodystrophyStudies of the same condition, open and under way.
- 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
- Other
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William A Gahl, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00889174
- Sponsor's protocol ID
- 090128
- Other IDs
- 09-HG-0128
- Status last verified
- 1 Aug 2018
- First submitted
- 25 Apr 2009
- Last updated
- 3 Aug 2018
- Results posted
- No
Publications
Linnankivi TT, Autti TH, Pihko SH, Somer MS, Tienari PJ, Wirtavuori KO, Valanne LK. 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images. J Magn Reson Imaging. 2003 Oct;18(4):414-9. doi: 10.1002/jmri.10383.
PubMed 14508777Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ, Fox PT. Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency. Am J Med Genet. 1997 Jul 25;74(4):422-31. doi: 10.1002/(sici)1096-8628(19970725)74:43.0.co;2-k.
PubMed 9259379Ugur SA, Tolun A. A deletion in DRCTNNB1A associated with hypomyelination and juvenile onset cataract. Eur J Hum Genet. 2008 Feb;16(2):261-4. doi: 10.1038/sj.ejhg.5201935. Epub 2007 Oct 10.
PubMed 17928815
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Leukodystrophies of Unknown Cause
- ClinicalTrials.gov ID
- NCT00889174
- Acronym / sponsor ID
- 090128
- Conditions
- Leukodystrophy, Leukoencephalopathy
- Keywords
- Genetic Disorders of the White Matter, Leukodystrophies, Myelin, White Matter Disorder, Genetic Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 24 Apr 2009
- Study completion
- 1 Aug 2018
- First posted
- 28 Apr 2009 (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.
Background:
- A leukodystrophy is a disease affecting the white matter of the brain. The white matter conducts electricity from one part of the brain to the other. If the insulation, or myelin, is damaged, the brain s electrical pathways will not work properly. Researchers are trying to identify what causes leukodystrophy.
Objectives:
- To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genetic studies, and neurophysiologic and neuroimaging studies in patients with unclassified leukodystrophies to comprehensively characterize such patients and obtain comparative clinical profiles.
- To collect detailed clinical characterizations, including histories, physical examinations, biochemical tests, genomic and proteomic tissue, and neurophysiologic and neuroimaging studies in patients with known leukodystrophies to investigate the underlying pathogenesis of these disorders.
- To better understand leukodystrophies of unknown cause and to identify the part of the DNA of the patient with leukodystrophy that is causing the problem.
Eligibility:
- Any individual with a known or suspected leukodystrophy is eligible to participate in this protocol, including
- Patients with white matter disease that is unclassified or of unknown cause, including but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination, and leukoencephalopathies with brainstem involvement.
- Parents or siblings of these subjects.
- Exclusion criteria include patients too ill to travel to the Clinical Center and patients for whom the leukoencephalopathy is felt to be secondary to an acquired cause (for example, traumatic or infectious).
Design:
- Patients will be seen either as an inpatient or outpatient depending on the tests that are planned. Patients may need to stay at the Clinical Center for 3 to 5 days.
- The following tests will be conducted as part of standard clinical care:
- Physical and neurological examinations, including blood and urine tests.
- Magnetic resonance based studies to produce a picture of the patient s brain (under general anesthesia).
- Spinal tap to measure chemicals in the spinal fluid (under general anesthesia in young children).
- Nerve biopsy, if the peripheral nerves are affected, or muscle biopsy, if the cells called the mitochondria or the muscles are involved (both under general anesthesia).
- The following studies may be performed as part of participation in the research:
- Blood, urine, spinal fluid, or muscle to understand the proteins, DNA, and molecules in these tissues.
- Skin biopsy to grow (in culture) skin cells and to analyze the skin microscopically.
- DNA studies to find new genes responsible for leukodystrophies and to better understand these diseases.
- Participation should be based on an interest to help further the research on leukodystrophies. Specific information about a patient s present or future health risks may not be gained.
Detailed description
Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of 1:5000 live births. As many as 50% of patients with white matter disease remain undiagnosed after conventional neuroimaging, biochemical and genetic testing, and therefore have unclassified leukodystrophies. Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood: many are systemic abnormalities that manifest only in white matter. The purpose of this study is to: (a) define novel homogeneous groups of patients with leukodystrophy and work toward finding the cause of these disorders and (b) establish disease mechanisms in selected classified leukodystrophies. In order to achieve these goals, patients with leukodystrophy will be analyzed by clinical, neurophysiological, biochemical and genetic means. For goal (a), patients would have been diagnosed as having an unclassified leukodystrophy or no known cause of their leukodystrophy at outside centers. At the Clinical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. For goal (b), selected leukodystrophies with a defined genetic cause will be selected for further mechanistic study, using clinical and laboratory tools to establish increased understanding of the underlying pathophysiology. 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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 1 month to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with white matter disease that is unclassified or of unknown cause, including, but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination and leukoencephalopathies with brainstem involvement.
- Parents or siblings of these subjects
Key exclusion criteria (2 listed)
- Patients meeting above criteria but too ill to travel to the clinical center. In that case, consideration will be given to enrolling them for the collection of medical records and samples only.
- Patients meeting above criteria, but where the leukoencephalopathy is felt to be secondary to an acquired cause, for example traumatic or infectious.
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
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
- Background: PubMed 14508777Linnankivi TT, Autti TH, Pihko SH, Somer MS, Tienari PJ, Wirtavuori KO, Valanne LK. 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images. J Magn Reson Imaging. 2003 Oct;18(4):414-9. doi: 10.1002/jmri.10383.
- Background: PubMed 9259379Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ, Fox PT. Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency. Am J Med Genet. 1997 Jul 25;74(4):422-31. doi: 10.1002/(sici)1096-8628(19970725)74:43.0.co;2-k.
- Background: PubMed 17928815Ugur SA, Tolun A. A deletion in DRCTNNB1A associated with hypomyelination and juvenile onset cataract. Eur J Hum Genet. 2008 Feb;16(2):261-4. doi: 10.1038/sj.ejhg.5201935. Epub 2007 Oct 10.
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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. This study is not recruiting at the moment.
William A Gahl, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site 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 Leukoencephalopathy, run by National Human Genome Research Institute (NHGRI) at 1 site 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 2 inclusion and 2 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: finished, as of the sponsor's last update on 3 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00889174, which also lists 3 linked publications.
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 3 Aug 2018.