Nervous System Degeneration in Glycosphingolipid Storage Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00029965
First received: January 27, 2002
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

This study will evaluate children with glycosphingolipid (GSL) storage disorders to investigate brain changes that cause nervous system degeneration. No experimental treatments are offered in this study; participants will receive standard medical care for their disease. The information from this study may help researchers develop new therapies for these disorders and monitor the effects of treatment.

Patients of any age with Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis, or type 2 Gaucher disease may be eligible for this study.

Participants will be admitted to the NIH Clinical Center for 4 to 5 days every 6 months for a clinical evaluation involving the following tests and procedures:

  • Medical history
  • Physical, neurologic, and eye examinations
  • Developmental evaluations by a physical therapist, nutritionist and psychologist
  • Blood tests to check nutritional status, liver and kidney function, and, in patients treated for seizures, level of anti-seizure drugs. Some blood will also be used for research purposes.
  • Urinalysis to check urine sugar levels and kidney function
  • Skin biopsy to obtain cells to grow in culture. The biopsy area is numbed with an anesthetic cream and a 1/8-inch piece of skin is removed with a circular punch and scissors.
  • Genetic analysis of DNA to screen for mutations responsible for the patient s GSL storage disorder
  • Magnetic resonance imaging (MRI) brain scans. Children with type 2 Gaucher disease, Sandhoff disease and GM1 gangliosidosis will also have liver and spleen scans. Brain scans will be done every 6 months the first year. After that, they may be done less often, depending on the results. For the MRI, the child lies still in a narrow cylinder (the scanner). A magnetic field and radio waves are used to produce pictures of the organs under study. (Children will be sedated for MRI. Children who cannot be sedated will not have this test.)
  • Electroencephalogram (EEG) to measure electrical activity of the brain and detect possible seizures. For this test, electrodes (small metal discs attached to wires) are attached to the child s head with a paste and the brain waves (electrical activity) are recorded while the child rests quietly.
  • Brainstem auditory evoked response (BAER) to measure hearing. Electrodes are attached to the child s head (similar to the EEG procedure) and the brain waves are recorded when a sound stimulation is given.
  • Lumbar puncture (spinal tap) to study proteins in the cerebrospinal fluid, which bathes the brain and spinal cord. A needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle. This test is done under anesthetic at the same time the MRI is done. If the child cannot be sedated, a local anesthetic will be used.

Condition
Gangliosidoses
Gaucher Disease

Study Type: Observational
Official Title: Investigation of Neurodegeneration in the Glycosphingolipid Storage Disorders

Resource links provided by NLM:


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

Estimated Enrollment: 150
Study Start Date: January 2002
Detailed Description:

The GM1 and GM2 gangliosidoses are lysosomal storage disorders that primarily affect the brain and are uniformly fatal. No effective therapy for patients with these diseases has yet been demonstrated. Historically, since these disorders are fatal very little natural history information or disease characterization using modern medical techniques has been collected. This information is vital in order to establish the pattern of disease progression and to identify clinical, biochemical and biophysical markers that can be used as endpoints in future therapeutic trials.

This protocol aims to study the natural history of the GM1 and GM2 gangliosidoses in affected individuals of all ages, races and genders using medical technologies including MRI/MRS, hearing evaluation and auditory evoked response testing, and EEG, as well as subspecialty evaluations in rehabilitative medicine, ophthalmology, speech language pathology, neurology, and psychology. Biomarkers of disease progression will be explored in CSF and blood samples for correlation with disease staging. Fibroblast cultures will be established for testing potential therapeutic agents. We hypothesize that relevant biomarkers will correlate with disease progression and will shed light on the pathophysiology of disease progression in these devastating disorders.

As a means of acquiring additional information, subjects or their parents will also be asked to complete a questionnaire regarding their medical and developmental history, initial clinical presentation of the disease and steps toward diagnosis. At their request, the same questionnaire will be sent to families who do not wish to undergo clinical evaluation at the NIH, who are too unstable to travel, or whose children are already deceased.

  Eligibility

Ages Eligible for Study:   6 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Individuals greater than 6 months of age with GM1 or GM2 gangliosidosis documented by enzyme deficiency and/or mutation analysis in a CLIA-approved laboratory

EXCLUSION CRITERIA:

  • Individuals who in the opinion of the principal investigator are too medically fragile to travel safely to the NIH for evaluation
  • Individuals unable to comply with the protocol
  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: NCT00029965

Contacts
Contact: Cynthia J Tifft, M.D. (301) 451-8485 cynthiat@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Cynthia J Tifft, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00029965     History of Changes
Other Study ID Numbers: 020107, 02-HG-0107
Study First Received: January 27, 2002
Last Updated: July 16, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Tay-Sachs
Lysosomal Storage Disorders
Lysosomal Storage Disorder
Sandhoff
Gaucher

Additional relevant MeSH terms:
Gaucher Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Nervous System Diseases
Gangliosidoses
Lipid Metabolism, Inborn Errors
Lipidoses
Metabolism, Inborn Errors
Sphingolipidoses

ClinicalTrials.gov processed this record on October 20, 2014