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A Natural History Study of the Gangliosidoses

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
National Center for Advancing Translational Science (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00668187
First received: April 25, 2008
Last updated: August 10, 2016
Last verified: August 2016
  Purpose

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

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Natural History Study of the Gangliosidoses

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Change in Child Developmental Status as Assessed by Neuropsychological Tests [ Time Frame: Upon enrollment; then at 12, 24, 36, 48 and 60 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Ascertainment of Enzyme Activity Levels [ Time Frame: Upon enrollment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 52
Study Start Date: December 2010
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668187

Contacts
Contact: Evelyn S. Redtree, M.S. 612-625-0974 eredtree@umn.edu

Locations
United States, Minnesota
University of Minnesota - Pediatric Genetics and Metabolism Recruiting
Minneapolis, Minnesota, United States, 55455
Principal Investigator: Jeanine R. Utz, PharmD         
Sub-Investigator: Chester B. Whitley, MD, PhD         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Rare Diseases Clinical Research Network
National Center for Advancing Translational Science (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Jeanine R. Utz, PharmD University of Minnesota - Fairview
  More Information

Additional Information:
Publications:

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00668187     History of Changes
Other Study ID Numbers: 0801M24964  U54NS065768 
Study First Received: April 25, 2008
Last Updated: August 10, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
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.

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Tay-Sachs disease
Late Onset Tay-Sachs disease
hexosaminidase A deficiency
hexosaminidase A and B deficiency
infantile Tay-Sachs disease
adult-onset Tay-Sachs disease
juvenile Tay-Sachs disease
GM2 gangliosidosis
Sandhoff disease
LOTS
prospective
natural history
GM1 gangliosidosis
gangliosidoses
β-galactosidase
β-galactosidase deficiency
hexosaminidase
hexosaminidase deficiency
Tay-Sachs
Sandhoff
juvenile Tay-Sachs
late onset Tay-Sachs
juvenile Sandhoff
juvenile Sandhoff disease

Additional relevant MeSH terms:
Tay-Sachs Disease
Gangliosidosis, GM1
Sandhoff Disease
Gangliosidoses
Gangliosidoses, GM2
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

ClinicalTrials.gov processed this record on September 29, 2016