The Classification and Cause of Leukodystrophies of Unknown Cause

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001671
First received: November 3, 1999
Last updated: December 16, 2008
Last verified: December 2008
  Purpose

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.


Condition
Lysosomal Storage Disease

Study Type: Observational
Official Title: The Nosology and Etiology of Leukodystrophies of Unknown Cause

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 400
Study Start Date: September 1997
Estimated Study Completion Date: December 2008
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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. 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.
    2. First -degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients)

EXCLUSION CRITERIA:

  1. Refusal to sign the protocol consent form.
  2. Candidates who are unable to travel to the National Institutes of Health Clinical Center.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001671

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
Childrens National Medical Center
Washington, District of Columbia, United States
France
Institut National de la Sante' et de la Recherche Medicale
Clermont-Ferrand, Cedex, France, 63001
Israel
Tel Aviv University
Tel Aviv, Israel
Netherlands
Academiseh Ziuekenhuis Vrije Universiteit
Amsterdam, Netherlands
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001671     History of Changes
Other Study ID Numbers: 970170, 97-N-0170
Study First Received: November 3, 1999
Last Updated: December 16, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
White Matter
Myelin
Degenerative Diseases
Genetic
Oligodendrocytes
Leukodystrophy

Additional relevant MeSH terms:
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 22, 2014