Clinical trial NCT00668187: A Natural History Study of the Gangliosidoses
Official title: A Natural History Study of the Gangliosidoses
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tay-Sachs Disease
Sandhoff Disease
Late Onset Tay-Sachs Disease
GM1 Gangliosidosis
GM2 Gangliosidosis
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
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: National Center for Advancing Translational Sciences (NCATS)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Lysosomal Disease Network
First posted: 2008-04-29
Enrollment: 52
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

Detailed description: 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.

Eligibility criteria: 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.

Exclusion Criteria:

1. There are no exclusion criteria, beyond a desire not to participate.

Primary outcomes:
measure: Change in Child Developmental Status as Assessed by Neuropsychological Tests
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
Secondary outcomes:
measure: Ascertainment of Enzyme Activity Levels
timeFrame: Upon enrollment
measure: Medication Regime
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
measure: Clinical Assessments
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
measure: Changes in Child Brain Structure Development and Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
measure: Identification of Genetic Mutation(s)
timeFrame: Upon Enrollment
measure: Changes in Chitotriosidase Enzyme Activity Levels
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
measure: Ascertainment of Ganglioside Levels
timeFrame: Upon enrollment
measure: Change in Adult Neurocognitive Status as Assessed by Neuropsychological Tests
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
measure: Changes in Adult Brain Structure Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination
timeFrame: Upon enrollment; then at 12, 24, 36, 48 and 60 months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota - Pediatric Genetics and Metabolism
state: Minnesota
Study officials:
affiliation: University of Minnesota - Fairview
name: Jeanine R. Jarnes, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.