A Natural History Study of the Gangliosidoses

NCT ID: NCT00668187

Last Updated: 2025-02-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

52 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-12-31

Study Completion Date

2027-03-01

Brief Summary

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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.

Detailed Description

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The infantile form of GM2 and GM1 gangliosidosis diseases ("classic" infantile) is the most common. Infants with Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis appear normal at birth, but at approximately 6-10 months of age begin to manifest progressive weakness and loss of muscle strength, such as loss of the ability to sit up or turn over. They may evidence deafness, and display decreased attentiveness. This is followed by rapid deterioration of motor skills and slowed mental development (neurodegeneration), often with seizures. Retinal involvement leads to visual impairment and eventual blindness. Death typically occurs by the age of five. Currently there is no treatment for Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis.

Late Onset Tay-Sachs disease ("LOTS") occurs in patients beginning in their twenties or thirties, and is characterized by poor motor coordination and psychotic behaviors. Patients with LOTS also have decreased life expectancy, although to a lesser degree than those with infantile or juvenile Tay-Sachs or Sandhoff diseases. Currently there is no treatment for LOTS.

This study is comprised of two different 'arms.' The first arm, entitled Aim 1, will focus on the developmental course of infantile and juvenile Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis. Longitudinal data from individuals with these diseases will be collected in order to delineate the natural history of these diseases. This data will help to objectify disease progression, and can be used to create a disease stage and severity index.

The second arm, entitled Aim 2, will focus on LOTS and will seek to understand the progression of central nervous system disease, with special focus upon cerebellar and frontal systems. This will be accomplished by using quantitative methods including neuroimaging and neuropsychological measures that explore motor and executive functions, visual-spatial and emotional-behavioral dysfunction.

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

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

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rare Diseases Clinical Research Network

NETWORK

Sponsor Role collaborator

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Lysosomal Disease Network

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeanine R. Jarnes, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota - Fairview

Locations

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University of Minnesota - Pediatric Genetics and Metabolism

Minneapolis, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jeanine R. Jarnes, PharmD

Role: CONTACT

612-626-5131

Facility Contacts

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Jeanine R. Jarnes, PharmD

Role: primary

612-626-5131

References

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Toro C, Shirvan L, Tifft C. HEXA Disorders. 1999 Mar 11 [updated 2020 Oct 1]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1218/

Reference Type BACKGROUND
PMID: 20301397 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8230592 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15714079 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9547461 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15956171 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2939718 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15210895 (View on PubMed)

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.

Reference Type RESULT
PMID: 25557439 (View on PubMed)

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.

Reference Type RESULT
PMID: 28476546 (View on PubMed)

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.

Reference Type RESULT
PMID: 29352662 (View on PubMed)

Related Links

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http://www.rarediseasesnetwork.org/index.htm

Homepage of the Rare Diseases Clinical Research Network

https://www.genome.gov/glossary/

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.

https://www.rarediseasesnetwork.org/LDN/

The Lysosomal Disease Network's page on the Rare Diseases Clinical Research Network's web site

Other Identifiers

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U54NS065768

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0801M24964

Identifier Type: -

Identifier Source: org_study_id

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