A Natural History Study of the Gangliosidoses

NCT00668187 | Recruiting DMC

• 2 other identifiers: 0801M24964U54NS065768
• Study Type: observational
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: To characterize and describe disease progression and heterogeneity of the gangliosidosis diseases. This research study seeks to develop a quantitative method to delineate disease progression for the gangliosidosis diseases (Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis) in order to better understand the natural history and heterogeneity of these diseases. Such a quantitative method will also be essential for evaluating any treatments that may become available in the future, such as gene therapy. The data from this study will be necessary to provide end-points for future therapies, guide medical decisions about treatment, provide objective measurement of treatment outcomes, and accurately inform parents regarding potential outcomes.

Conditions

Sandhoff Disease; GM1 Gangliosidosis; GM2 Gangliosidosis; Tay-Sachs Disease; Late Onset Tay-Sachs Disease

Keywords

Tay-Sachs disease; Sandhoff disease; Late Onset Tay-Sachs disease; LOTS; hexosaminidase A deficiency; hexosaminidase A and B deficiency; infantile Tay-Sachs disease; adult-onset Tay-Sachs disease; prospective; natural history; GM1 gangliosidosis; gangliosidoses; β-galactosidase; β-galactosidase deficiency; hexosaminidase; hexosaminidase deficiency; Tay-Sachs; Sandhoff; juvenile Tay-Sachs; juvenile Tay-Sachs disease; late onset Tay-Sachs; juvenile Sandhoff; juvenile Sandhoff disease; GM2 gangliosidosis

Outcome Measures

Primary Outcomes (1)

• Change in Child Developmental Status as Assessed by Neuropsychological Tests

  Neuropsychological testing data will be collected at baseline and annually, that measure fine and gross motor skills, visual tracking and attention, verbal and non-verbal communication, and emotional and social behaviors. For infantile and juvenile Tay-Sachs disease, Sandhoff disease and GM1 gangliosidosis-affected subjects, age- and ability-appropriate neurobehavioral and neurodevelopmental testing will include instruments such as the Bayley Scales of Infant Development (Third Edition), and the Vineland Adaptive Behavior Scales.

  Upon enrollment; then at 12, 24, 36, 48 and 60 months

Secondary Outcomes (9)

• Ascertainment of Enzyme Activity Levels

  Upon enrollment

• Medication Regime

  Upon enrollment; then at 12, 24, 36, 48 and 60 months

• Clinical Assessments

  Upon enrollment; then at 12, 24, 36, 48 and 60 months

• Changes in Child Brain Structure Development and Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination

  Upon enrollment; then at 12, 24, 36, 48 and 60 months

• Identification of Genetic Mutation(s)

  Upon Enrollment

Study Arms (1)

Gangliosidosis Diseases Study Population

This study observes one cohort: 42 infantile or juvenile Tay-Sachs disease, Sandhoff disease, or GM1 gangliosidosis affected subjects; and 10 late-onset gangliosidosis disease affected subjects.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any infant or juvenile with Tay-Sachs disease, Sandhoff disease, or GM1 gangliosidosis; and any adult with a late-onset gangliosidosis disease

You may qualify if:

• Subjects must have a documented gangliosidosis disease.
• Subjects must be able to complete appropriate neuropsychological and neurobehavioral assessments.
• Late-onset gangliosidosis subjects must be able to tolerate a head MRI.

Sponsors & Collaborators

• University of Minnesota: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Lysosomal Disease Network: collaborator

Study Sites (1)

University of Minnesota - Pediatric Genetics and Metabolism

Minneapolis, Minnesota, 55455, United States

RECRUITING

Related Publications (10)

• Toro C, Shirvan L, Tifft C. HEXA Disorders. 1999 Mar 11 [updated 2020 Oct 1]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1218/

  PMID: 20301397 BACKGROUND

• Kaback M, Lim-Steele J, Dabholkar D, Brown D, Levy N, Zeiger K. Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network. JAMA. 1993 Nov 17;270(19):2307-15.

  PMID: 8230592 BACKGROUND

• Neudorfer O, Pastores GM, Zeng BJ, Gianutsos J, Zaroff CM, Kolodny EH. Late-onset Tay-Sachs disease: phenotypic characterization and genotypic correlations in 21 affected patients. Genet Med. 2005 Feb;7(2):119-23. doi: 10.1097/01.gim.0000154300.84107.75.

  PMID: 15714079 BACKGROUND

• MacQueen GM, Rosebush PI, Mazurek MF. Neuropsychiatric aspects of the adult variant of Tay-Sachs disease. J Neuropsychiatry Clin Neurosci. 1998 Winter;10(1):10-9. doi: 10.1176/jnp.10.1.10.

  PMID: 9547461 BACKGROUND

• Frey LC, Ringel SP, Filley CM. The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis. Arch Neurol. 2005 Jun;62(6):989-94. doi: 10.1001/archneur.62.6.989.

  PMID: 15956171 BACKGROUND

• Navon R, Argov Z, Frisch A. Hexosaminidase A deficiency in adults. Am J Med Genet. 1986 May;24(1):179-96. doi: 10.1002/ajmg.1320240123.

  PMID: 2939718 BACKGROUND

• Zaroff CM, Neudorfer O, Morrison C, Pastores GM, Rubin H, Kolodny EH. Neuropsychological assessment of patients with late onset GM2 gangliosidosis. Neurology. 2004 Jun 22;62(12):2283-6. doi: 10.1212/01.wnl.0000130498.19019.02.

  PMID: 15210895 BACKGROUND

• Utz JR, Crutcher T, Schneider J, Sorgen P, Whitley CB. Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses. Mol Genet Metab. 2015 Feb;114(2):274-80. doi: 10.1016/j.ymgme.2014.11.015. Epub 2014 Dec 6.

  PMID: 25557439 RESULT

• Jarnes Utz JR, Kim S, King K, Ziegler R, Schema L, Redtree ES, Whitley CB. Infantile gangliosidoses: Mapping a timeline of clinical changes. Mol Genet Metab. 2017 Jun;121(2):170-179. doi: 10.1016/j.ymgme.2017.04.011. Epub 2017 Apr 29.

  PMID: 28476546 RESULT

• Nestrasil I, Ahmed A, Utz JM, Rudser K, Whitley CB, Jarnes-Utz JR. Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Mol Genet Metab. 2018 Feb;123(2):97-104. doi: 10.1016/j.ymgme.2017.12.432. Epub 2017 Dec 20.

  PMID: 29352662 RESULT

Related Links

• Homepage of the Rare Diseases Clinical Research Network
• Talking Glossary of Genetic Terms from the National Human Genome Research Institute. (Uses Adobe Flash plugin.) This Talking Glossary is available as an app for mobile devices, from a link on this page.
• The Lysosomal Disease Network's page on the Rare Diseases Clinical Research Network's web site

MeSH Terms

Conditions

Tay-Sachs Disease; Sandhoff Disease; Gangliosidosis, GM1; Gangliosidoses, GM2; Gangliosidoses; Tay-Sachs Disease, Juvenile

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Jeanine R. Jarnes, PharmD

  University of Minnesota - Fairview

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeanine R. Jarnes, PharmD

CONTACT

612-626-5131; utzx0002@umn.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 29, 2008
• Study Start: December 1, 2010
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)