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The Classification and Cause of Leukodystrophies of Unknown Cause

Primary Purpose

Lysosomal Storage Disease

Status
Completed
Phase
Locations
International
Study Type
Observational
Intervention
Sponsored by
National Institute of Neurological Disorders and Stroke (NINDS)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Lysosomal Storage Disease focused on measuring White Matter, Myelin, Degenerative Diseases, Genetic, Oligodendrocytes, Leukodystrophy

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: Candidates for participation in the protocol will be patients of all ages with clinical and radiographic signs of leukodystrophy who do not have a specific etiology despite a previous comprehensive workup. The preceding investigation would have excluded the following: adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease, Canavan disease, a well-defined amino acid organic acid disorder, or a systemic mitochondrial cytopathy. First -degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients) EXCLUSION CRITERIA: Refusal to sign the protocol consent form. Candidates who are unable to travel to the National Institutes of Health Clinical Center.

Sites / Locations

  • University of California, San Francisco
  • Childrens National Medical Center
  • Institut National de la Sante' et de la Recherche Medicale
  • Tel Aviv University
  • Academiseh Ziuekenhuis Vrije Universiteit

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
June 30, 2017
Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT00001671
Brief Title
The Classification and Cause of Leukodystrophies of Unknown Cause
Official Title
The Nosology and Etiology of Leukodystrophies of Unknown Cause
Study Type
Observational

2. Study Status

Record Verification Date
December 15, 2008
Overall Recruitment Status
Completed
Study Start Date
September 9, 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 15, 2008 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

5. Study Description

Brief Summary
Leukodystrophy is a disease of the white matter of the brain. White matter is the portion of the brain responsible for conducting electrical impulses from one area of the brain to the other. Insulating cells called myelin cover the brain and nerve cells in the white matter. If myelin becomes damaged electrical information cannot be transferred properly. Many patients suffering from leukodystrophies do not fit the description of any of the defined types of leukodystrophies and are therefore considered to have a leukodystrophy of unknown cause. The purpose of this study is to define groups of patients with leukodystrophies and to work toward finding the cause of the disorders. In order to do this, researchers will analyze patients with leukodystrophies of unknown causes. Patients will undergo clinical, neurophysiologic, biochemical, and genetic examinations and tests. Researchers believe that by studying these patients and their disorders they will be able to better understand the causes of myelin destruction, and eventually lead to effective treatments for these disorders.
Detailed Description
Patients with leukodystrophies (LDs) of unknown etiology are a heterogeneous group but constitute the second largest group of genetic white matter diseases. The purpose of this study is to: (a) define novel homogeneous groups of patients with LDs and (b) work toward finding the cause of these disorders. In order to achieve these goals, patients with LDs of unknown cause will be analyzed clinically, neurophysiologically, biochemically and genetically. Patients would have been diagnosed as having no known leukodystrophies 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. Patients will be followed for 3 years. Patients will be screened for mutations in genes coding for structural myelin proteins. In some patients in whom all tests yielded no information regarding the etiology of their disease, open brain biopsy will be considered. Brain biopsy tissue will be evaluated using a novel combination of approaches including detailed pathological, immunohistochemical, and biochemical analysis of myelin proteins and lipids. Oligodendroglial biology and expression of myelin genes in the brain will also be investigated in situ. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lysosomal Storage Disease
Keywords
White Matter, Myelin, Degenerative Diseases, Genetic, Oligodendrocytes, Leukodystrophy

7. Study Design

Enrollment
400 (false)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Candidates for participation in the protocol will be patients of all ages with clinical and radiographic signs of leukodystrophy who do not have a specific etiology despite a previous comprehensive workup. The preceding investigation would have excluded the following: adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease, Canavan disease, a well-defined amino acid organic acid disorder, or a systemic mitochondrial cytopathy. First -degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients) EXCLUSION CRITERIA: Refusal to sign the protocol consent form. Candidates who are unable to travel to the National Institutes of Health Clinical Center.
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Childrens National Medical Center
City
Washington, D.C.
State/Province
District of Columbia
Country
United States
Facility Name
Institut National de la Sante' et de la Recherche Medicale
City
Clermont-Ferrand
State/Province
Cedex
ZIP/Postal Code
63001
Country
France
Facility Name
Tel Aviv University
City
Tel Aviv
Country
Israel
Facility Name
Academiseh Ziuekenhuis Vrije Universiteit
City
Amsterdam
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
7692130
Citation
Aicardi J. The inherited leukodystrophies: a clinical overview. J Inherit Metab Dis. 1993;16(4):733-43. doi: 10.1007/BF00711905.
Results Reference
background
PubMed Identifier
8122885
Citation
Schiffmann R, Moller JR, Trapp BD, Shih HH, Farrer RG, Katz DA, Alger JR, Parker CC, Hauer PE, Kaneski CR, et al. Childhood ataxia with diffuse central nervous system hypomyelination. Ann Neurol. 1994 Mar;35(3):331-40. doi: 10.1002/ana.410350314.
Results Reference
background
PubMed Identifier
9153528
Citation
Schiffmann R, Tedeschi G, Kinkel RP, Trapp BD, Frank JA, Kaneski CR, Brady RO, Barton NW, Nelson L, Yanovski JA. Leukodystrophy in patients with ovarian dysgenesis. Ann Neurol. 1997 May;41(5):654-61. doi: 10.1002/ana.410410515.
Results Reference
background
PubMed Identifier
28748214
Citation
McNeill N, Nasca A, Reyes A, Lemoine B, Cantarel B, Vanderver A, Schiffmann R, Ghezzi D. Functionally pathogenic EARS2 variants in vitro may not manifest a phenotype in vivo. Neurol Genet. 2017 Jul 14;3(4):e162. doi: 10.1212/NXG.0000000000000162. eCollection 2017 Aug.
Results Reference
derived

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The Classification and Cause of Leukodystrophies of Unknown Cause

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