A Natural History Study of the Gangliosidoses
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| ClinicalTrials.gov Identifier: NCT00668187 |
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Recruitment Status :
Recruiting
First Posted : April 29, 2008
Last Update Posted : March 7, 2023
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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.
| Condition or disease |
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| Tay-Sachs Disease Sandhoff Disease Late Onset Tay-Sachs Disease GM1 Gangliosidosis GM2 Gangliosidosis |
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.
| Study Type : | Observational |
| Estimated Enrollment : | 52 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | A Natural History Study of the Gangliosidoses |
| Actual Study Start Date : | December 2010 |
| Estimated Primary Completion Date : | March 1, 2027 |
| Estimated Study Completion Date : | March 1, 2027 |
| Group/Cohort |
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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.
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- Change in Child Developmental Status as Assessed by Neuropsychological Tests [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]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.
- Ascertainment of Enzyme Activity Levels [ Time Frame: Upon enrollment ]If either of the following diagnostic measures have been performed in the course of subjects' clinical care not connected with this study, the resulting data will be collected: for Tay-Sachs and Sandhoff disease-affected patients, levels of hexosaminidase enzyme activity; or for GM1 gangliosidosis-affected patients, levels of β-galactosidase enzyme activity. Determinations of these enzyme activity levels are a requisite part of the diagnostic process in all of the gangliosidosis diseases.
- Medication Regime [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]If any medications are given to subjects during the course of subjects' clinical care not connected with this study, the medications will be identified, quantified and recorded.
- Clinical Assessments [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]
Clinical assessments will be performed that measure initial symptomology, along with the appearance and evolution of symptoms over time. For infants and juveniles, these may include: evaluation of motor control, gain and/or loss of developmental milestones, hyperacusis, seizures, macrocephaly, the appearance of retinal "cherry-red spots" ascertained by ocular exam, personal interaction, and reflexes.
For adults, assessments may include: coordination, psychological disorder, verbal skills, muscle wasting with weakness, fasciculations, and posture abnormalities.
- Changes in Child Brain Structure Development and Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]For infantile and juvenile Tay-Sachs disease, Sandhoff disease and GM1 gangliosidosis-affected subjects, if any MRI brain imaging is performed during the course of subjects' clinical care not connected with this study, these MRI brain imaging data will be captured for this study. Any developmental abnormality, and the volumes of specific brain structures imaged, will be measured and the resulting data recorded. If data from multiple MRI examinations performed at different times in any given patient's life become available, the resulting brain structure measurements will be compared across time, and analyzed in order to reveal progressive changes in brain structure, if any have occurred.
- Identification of Genetic Mutation(s) [ Time Frame: Upon Enrollment ]If any subject's genetic mutation(s) that are responsible for their gangliosidosis disease are identified during the course of subject's clinical care not connected with this study, that genetic mutation information will be collected for this study.
- Changes in Chitotriosidase Enzyme Activity Levels [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]If the following biomarker measures are performed in the course of subjects' clinical care not connected with this study, the resulting data will be collected: plasma and/or cerebrospinal fluid chitotriosidase enzyme activity levels. If these measures are performed repeatedly at different times in the course of subjects' clinical care not connected with this study, the resulting data will be collected each time.
- Ascertainment of Ganglioside Levels [ Time Frame: Upon enrollment ]If either of the following diagnostic measures have been performed in the course of subjects' clinical care not connected with this study, the resulting data will be collected: for Tay-Sachs and Sandhoff disease-affected patients, levels of GM2 ganglioside; or for GM1 gangliosidosis-affected patients, levels of GM1 ganglioside.
- Change in Adult Neurocognitive Status as Assessed by Neuropsychological Tests [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]For adult-onset gangliosidosis-affected subjects, neuropsychological testing will be performed at baseline and annually as part of this study. Neuropsychological testing data will be collected using instruments including, but not limited to, the Wechsler Abbreviated Scale of Intelligence and the Test of Variables of Attention ("TOVA"). The resulting data will be recorded and compared across time, and analyzed in order to reveal progressive changes in subjects' neurocognitive status, if any have occurred.
- Changes in Adult Brain Structure Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ]For adult-onset gangliosidosis-affected subjects, an MRI examination of the head will be performed at baseline and annually as part of this study. The volumes of specific brain structures imaged will be measured and recorded. These brain structure measurements will be compared across time, and analyzed in order to reveal progressive changes in brain structure, if any have occurred.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- 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.
Exclusion Criteria:
1. There are no exclusion criteria, beyond a desire not to participate.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00668187
| Contact: Jeanine R. Jarnes, PharmD | 612-626-5131 | utzx0002@umn.edu |
| United States, Minnesota | |
| University of Minnesota - Pediatric Genetics and Metabolism | Recruiting |
| Minneapolis, Minnesota, United States, 55455 | |
| Contact: Jeanine R. Jarnes, PharmD 612-626-5131 utzx0002@umn.edu | |
| Principal Investigator: Jeanine R. Jarnes, PharmD | |
| Sub-Investigator: Chester B. Whitley, MD, PhD | |
| Principal Investigator: | Jeanine R. Jarnes, PharmD | University of Minnesota - Fairview |
Publications of Results:
Other Publications:
| Responsible Party: | University of Minnesota |
| ClinicalTrials.gov Identifier: | NCT00668187 |
| Other Study ID Numbers: |
0801M24964 U54NS065768 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 29, 2008 Key Record Dates |
| Last Update Posted: | March 7, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management & Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |
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Gangliosidoses Tay-Sachs Disease Gangliosidosis, GM1 Gangliosidoses, GM2 Sandhoff Disease 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 Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders |