A Natural History Study of Hexosaminidase Deficiency
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, Sandhoff Disease, Late Onset Tay-Sachs Disease
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||A Natural History Study of Hexosaminidase Deficiency|
- 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.
- 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.
- MRI Brain Neuroimaging [ Time Frame: 5 years ] [ Designated as safety issue: No ]For Tay-Sachs and Sandhoff-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 of the head will be performed annually. The volumes of specific brain structures recorded from MRI (when available) will be measured.
- Clinical Assessments [ Time Frame: 5 Years ] [ Designated as safety issue: No ]Clinical assessments that measure initial symptomology along with the appearance and evolution of symptoms over time will be performed. For infants and juveniles, these may include: evaluation of motor control, gain and/or loss of developmental milestones, hyperacusis, seizures, macroencephaly, the appearance of cherry red spots on ocular exam, personal interaction, and reflexes. For adults, assessments may include: coordination, psychological disorder, verbal skills, muscle wasting with weakness, fasciculations, and posture abnormalities.
- 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.
|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)|
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 begin to manifest progressive weakness, loss of muscle strength such as sitting up or turning over, deafness, and decreased attentiveness at approximately 6-10 months. This is followed by rapid deterioration of motor 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, executive function, visual-spatial and emotional-behavioral dysfunction.
|Contact: Brenda Diethelm-Okita, MPAemail@example.com|
|United States, Minnesota|
|University of Minnesota - Pediatric Genetics and Metabolism||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator: Chester B. Whitley, PhD, MD|
|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|