Longitudinal Studies of Brain Structure and Function in MPS Disorders
Neurobehavioral function and quality of life are compromised in many patients with mucopolysaccharidosis (MPS) disorders. The long-term goals of this research are to: 1) more accurately inform patients/parents regarding potential neurobehavioral outcomes; 2) develop sensitive measures of disease progression and central nervous system (CNS) treatment outcome; and 3) help clinical researchers develop direct treatments for specific brain structures/functions. The investigators hypothesize that specific and localized neuroimaging and neuropsychological findings and their relationship will be distinct for each MPS disorder. It is further hypothesized that without treatment, functions will decline and structure will change over time in a predictable fashion, and will be related to locus of abnormality and stage of disease.
Mucopolysaccharidosis Type I
Mucopolysaccharidosis Type II
Mucopolysaccharidosis Type VI
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Longitudinal Studies of Brain Structure and Function in MPS Disorders|
- Change in Cognitive Ability (IQ) [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ] [ Designated as safety issue: No ]Age-appropriate IQ tests will be administered at baseline and during subject's annual visit.
- Change in Quality of Life [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ] [ Designated as safety issue: No ]Age-appropriate Quality of Life measures will be administered at baseline and during subject's annual visit.
- Change in Neuropsychological Status [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ] [ Designated as safety issue: No ]Memory, Attention, Visual Spatial, and Visual Motor functions will be assessed with age-appropriate measures administered at baseline and during subject's annual visit.
- Change in Emotional and Behavioral Health [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ] [ Designated as safety issue: No ]Age-appropriate measures of emotional and behavioral health will be administered at baseline and during subject's annual visit.
- Change Shown in Magnetic Resonance Imaging of the Brain [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ] [ Designated as safety issue: No ]Magnetic resonance imaging of each subject's brain will be performed at baseline and during subject's annual visit to acquire volumetric and diffusion tensor imaging (DTI) data. These data will be analyzed to identify any changes occurring over time.
- Change in Adaptive Functions [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ] [ Designated as safety issue: No ]Vineland Adaptive Behavior Scales, a measure of communication, daily living skills, socialization and motor function, will be administered at baseline and during subject's annual visit.
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
MPS I H (Hurler syndrome)
MPS IH (Hurler syndrome) patients who are undergoing transplantation or have had transplant in the past.
MPS I Attenuated
Patients diagnosed with either Hurler Scheie or Scheie syndrome on Enzyme Replacement Therapy (ERT)
Patients with Hunter syndrome who are on Enzyme Replacement Therapy
Patients with Maroteaux-Lamy syndrome who have either had hematopoietic cell transplant or are on enzyme replacement therapy
The mucopolysaccharidoses (MPS diseases) are lysosomal disorders (inborn errors of metabolism) that progressively affect most organ systems in the body, usually beginning in childhood. Recent treatment advances have produced amelioration of some of these malfunctions, but notably brain and bone have been difficult to effectively treat. This research addresses the brain abnormalities in the MPS disorders, about which little is known.
The objectives of this research are:
- to identify abnormalities of central nervous system (CNS) structure and function as well as to measure quality-of-life (QOL) in both treated and untreated MPS patients over time. The investigators will accomplish this through longitudinal studies of enrolled patients in designated centers in North America.
- to develop quantitative measurements of change, including direct measurement of neuropsychological function; surrogate MRI markers; and biomarkers to measure stage of disease and treatment outcomes.
- to examine the degree to which independent variables have an impact on both functional and structural outcome. Independent variables may include, but are not limited to: age at first treatment, severity of disease, types of medical abnormalities, nature of genetic mutation, medical events, and sensory abnormalities.
- to examine how treatments such as Enzyme Replacement Therapy (ERT), Hematopoietic Cell Transplant (HCT), substrate reduction, and other palliative and rehabilitative therapies differentially affect CNS structure and function, as well as the subject's quality of life.
|United States, California|
|Oakland Children's Hospital||Recruiting|
|Oakland, California, United States, 94609|
|Contact: Jo Ann Johnson 510-428-3885 ext 5421 JAJohnson@mail.cho.org|
|Principal Investigator: Paul Harmatz, M.D.|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Jueleah Expose-Spencer, MBA, MHCM 415-353-1248 Jueleah.Expose-Spencer@ucsfmedctr.org|
|Principal Investigator: Morton J. Cowan, M.D.|
|United States, Georgia|
|Atlanta, Georgia, United States, 30033|
|Contact: Stephanie Cagle, MS 404-778-8421 email@example.com|
|Principal Investigator: Suma Shankar, M.D.|
|United States, Minnesota|
|University of Minnesota||Enrolling by invitation|
|Minneapolis, Minnesota, United States, 55455|
|United States, New York|
|New York University||Recruiting|
|New York, New York, United States, 10016|
|Contact: Marissa Ferraris 212-263-0139 Marissa.Ferraris@nyumc.org|
|Principal Investigator: Heather Lau, M.D.|
|Hospital for Sick Children||Recruiting|
|Toronto, Ontario, Canada, M5G1X8|
|Contact: Margaret Macrell, RN 416-813-8367 firstname.lastname@example.org|
|Principal Investigator: Julian Raiman, M.D.|
|Principal Investigator:||Elsa G. Shapiro, Ph.D.||University of Minnesota - Clinical and Translational Science Institute|
|Study Director:||Kathleen Delaney||University of Minnesota - Clinical and Translational Science Institute|
|Study Chair:||Paul Harmatz, M.D.||Oakland Children's Hospital|
|Study Chair:||Julian Raiman, M.D.||Hospital for Sick Children, Toronto, Ontario, CA|
|Study Chair:||Morton Cowan, M.D.||University of California, San Francisco|
|Study Chair:||Suma Shankar, M.D.||Emory University|
|Study Chair:||Heather Lau, M.D.||New York University|