A Natural History Study of the Gangliosidoses

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00668187
First received: April 25, 2008
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

Hypothesis: To characterize and describe disease progression and heterogeneity in the hexosaminidase family of disorders.

This research study seeks to develop a quantitative method to delineate disease progression for the hexosaminidase disorders (Tay-Sachs, Sandhoff, and Late Onset Tay-Sachs diseases) in order to better understand the natural history and heterogeneity of disease. 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

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Natural History Study of Gangliosidosis and Other Hexosaminidase Deficiencies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Neuropsychological test results [ Time Frame: 5 years ] [ Designated as safety issue: No ]

    Neuropsychological testing data will be collected, that measure fine and gross motor skills, visual tracking and attention, verbal and non-verbal communication, and emotional and social behaviors. For Tay-Sachs and Sandhoff disease-affected subjects, age- and ability-appropriate neurobehavioral and neurodevelopmental testing will include instruments such as: Bayley Scales of Infant Development-Third Edition; The Infant and Toddler Health Questionnaire developed by Dr. Florian Eichler; and Quality of Life (CHQ or PROMIS parental assessment) questionnaire.

    For LOTS-affected subjects, neuropsychological testing data will be collected using instruments including Weschler Abbreviated Scale of Intelligence, Test of Variables of Attention, Neurotrax, Brief Symptom Inventory, Brief pain/quality of life inventory, and a LOTS questionnaire and quality-of-life assessment developed by Dr. Florian Eichler.



Secondary Outcome Measures:
  • BioMarker Measures [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    If any of the following measures are taken as a course of clinical care, the data will be collected: hexosaminidase enzyme levels; chitotriosidase levels; GM-2 ganglioside levels.

  • Medication Regime [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    If any medications are given during the course of clinical care, they will be identified, quantified and recorded.

  • Quality-of-Life Measurement Data [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    All subjects' quality-of-life measurement data will be repeatedly collected and collated over time.

  • Clinical Assessments [ Time Frame: 5 Years ] [ 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.

  • Assessment of Changes in Brain Structure, as ascertained by Magnetic Resonance Imaging (MRI) Examination [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    For Tay-Sachs and Sandhoff disease-affected subjects, if any MRI brain imaging is performed during clinical care of these patients, these clinical-care data will be captured for this study. For LOTS-affected subjects, an MRI examination of the head will be performed annually. The volumes of specific brain structures visible in the MRI results (when available) will be measured.


Estimated Enrollment: 30
Study Start Date: December 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Hexosaminidase Diseases Study Population
15 Tay-Sachs or Sandhoff disease affected subjects; and 15 Late Onset Tay-Sachs disease affected subjects

Detailed Description:

The infantile form of hexosaminidase deficiency disease (classic infantile) is the most common. Infants with Tay-Sachs or Sandhoff disease 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 or Sandhoff disease.

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 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 Tay-Sachs and Sandhoff disease. 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 create a disease stage and severity index. These indices will be used to evaluate untreated, and eventually treated, subjects.

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Any infant or juvenile with Tay-Sachs or Sandhoff disease; and Any adult with Late Onset Tay-Sachs disease

Criteria

Inclusion Criteria:

  1. Subjects must have a documented hexosaminidase disorder.
  2. Subjects must be able to complete appropriate neuropsychological and neurobehavioral tests.
  3. LOTS subjects must be able to tolerate an annual head MRI exam.

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: Brenda Diethelm-Okita, MPA 612-625-1594 dieth001@umn.edu

Locations
United States, Minnesota
University of Minnesota - Pediatric Genetics and Metabolism Recruiting
Minneapolis, Minnesota, United States, 55455
Principal Investigator: Chester B. Whitley, PhD, MD         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Chester B. Whitley, PhD, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Florian Eichler, MD Harvard University, Massachusetts General Hospital
  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: July 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
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

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

ClinicalTrials.gov processed this record on August 20, 2014