A Natural History Study of the Gangliosidoses
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.
Tay Sachs Disease
Late Onset Tay Sachs Disease
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||A Natural History Study of Gangliosidosis and Other Hexosaminidase Deficiencies|
- 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 Wechsler 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.
- 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 and recorded.
|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)|
Hexosaminidase Diseases Study Population
15 Tay-Sachs or Sandhoff disease affected subjects; and 15 Late Onset Tay-Sachs disease affected subjects
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00668187
|Contact: Brenda Diethelm-Okita, MPAfirstname.lastname@example.org|
|United States, Massachusetts|
|Harvard University, Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Florian Eichler, MD 617-726-6093 email@example.com|
|Sub-Investigator: Florian Eichler, MD|
|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|
|Principal Investigator:||Jeanine R. Utz, PharmD||University of Minnesota - Fairview|