Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

Myoclonus Clinical Trial

Official title:

Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00029965
• Other study ID #: 020107
• Secondary ID: 02-HG-0107
• Status: Recruiting
• Start date: February 6, 2002

Study information

• Verified date: June 12, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Jean M Johnston
• Phone: (240) 515-1448
• Email: johnstonjm[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Study description: This is a natural history study that will evaluate any patient with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Patients may be evaluated every 6 months for infantile onset disease, yearly for juvenile onset and approximately every two years for adult-onset disease as long as they are clinically stable to travel. Data will be evaluated serially for each patient, and cross-sectionally for patients of similar ages and genotypes. Genotype-phenotype correlations will be made where possible although these are rare disorders and the majority of the patients are compound heterozygotes. Objectives: To study the natural history and progression of neurodegeneration in individuals with glycosphingolipid storage disorders (GSL), GM1 and GM2 gangliosidosis, and glycoprotein (GP) disorders including sialidosis and galactosialidosis using clinical evaluation of patients and patient/parent surveys. To develop sensitive tools for monitoring disease progression. To identify biological markers in blood, cerebrospinal fluid, and urine that correlate with disease severity and progression and can be used as outcome measures for future clinical trials. To further understand and characterize the mechanisms of neurodegeneration in GSL and GP storage disorders across the spectrum of disease beginning with ganglioside storage in fetal life. Endpoints: Exploring the natural history of Lysosomal Storage Diseases and Glycoprotein Disorders Study Population: Patients with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Accrual ceiling is 200 participants. No exclusions based on age, gender, demographic group, or demographic location. Patients included in our study are those that are seen at the NIH Clinical Center, subjects that have only sent in blood samples, as well as those who complete the questionnaire or provided head circumference measures.

Description:

Study description: This is a natural history study that will evaluate any patient with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Patients may be evaluated every 6 months for infantile onset disease, yearly for juvenile onset and approximately every two years for adult-onset disease as long as they are clinically stable to travel. Data will be evaluated serially for each patient, and cross-sectionally for patients of similar ages and genotypes. Genotype-phenotype correlations will be made where possible although these are rare disorders and the majority of the patients are compound heterozygotes. Objectives: To study the natural history and progression of neurodegeneration in individuals with glycosphingolipid storage disorders (GSL), GM1 and GM2 gangliosidosis, and glycoprotein (GP) disorders including sialidosis and galactosialidosis using clinical evaluation of patients and patient/parent surveys. To develop sensitive tools for monitoring disease progression. To identify biological markers in blood, cerebrospinal fluid, and urine that correlate with disease severity and progression and can be used as outcome measures for future clinical trials. To further understand and characterize the mechanisms of neurodegeneration in GSL and GP storage disorders across the spectrum of disease beginning with ganglioside storage in fetal life. Endpoints: Exploring the natural history of Lysosomal Storage Diseases and Glycoprotein Disorders Study Population: Patients with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Accrual ceiling is 200 participants. No exclusions based on age, gender, demographic group, or demographic location. Patients included in our study are those that are seen at the NIH Clinical Center, subjects that have only sent in blood samples, as well as those who complete the questionnaire or provided head circumference measures.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

• 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

Related Conditions & MeSH terms

• Brain Atrophy
• Cherry Red Spot
• Myoclonus
• Neurological Regression

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Cantor RM, Roy C, Lim JS, Kaback MM. Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. II. Sandhoff disease gene frequencies in American Jewish and non-Jewish populations. Am J Hum Genet. 1987 Jul;41(1):16-26. — View Citation

Myerowitz R, Hogikyan ND. Different mutations in Ashkenazi Jewish and non-Jewish French Canadians with Tay-Sachs disease. Science. 1986 Jun 27;232(4758):1646-8. doi: 10.1126/science.3754980. — View Citation

Wada R, Tifft CJ, Proia RL. Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10954-9. doi: 10.1073/pnas.97.20.10954. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exploring the natural history of Glycoprotein Disorders	Exploring the natural history of Glycoprotein Disorders	Assessed one to every two years
Primary	Natural history of Lysosomal Storage Diseases	Exploring the natural history of Lysosomal Storage Diseases	Assessed one to every two years

External Links

•   NIH Clinical Center Detailed Web Page