Clinical trial NCT00029965: Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
Official title: Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neurological Regression
Myoclonus
Cherry Red Spot
Brain Atrophy
Keywords: Sialidosis
Lysosomal Storage
GM1 Gangliosidosis
GM2 Gangliosidosis
Natural History
Glycoprotein Disorders
Lysosomal Storage Disorder
Tay-Sachs
Sandhoff
Gaucher
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2002-01-28
Enrollment: 200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Lysosomal Storage Diseases and Glycoprotein Disorders.

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Exploring the natural history of Glycoprotein Disorders
timeFrame: Assessed one to every two years
measure: Natural history of Lysosomal Storage Diseases
timeFrame: Assessed one to every two years
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Human Genome Research Institute (NHGRI)
name: Cynthia J Tifft, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
citation: Daich Varela M, Zein WM, Toro C, Groden C, Johnston J, Huryn LA, d'Azzo A, Tifft CJ, FitzGibbon EJ. A sialidosis type I cohort and a quantitative approach to multimodal ophthalmic imaging of the macular cherry-red spot. Br J Ophthalmol. 2021 Jun;105(6):838-843. doi: 10.1136/bjophthalmol-2020-316826. Epub 2020 Aug 4.