Longitudinal Studies of Brain Structure and Function in MPS Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 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:
NCT01870375
First received: August 2, 2011
Last updated: July 24, 2015
Last verified: July 2015
  Purpose

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.


Condition
Mucopolysaccharidosis Type I
Mucopolysaccharidosis Type II
Mucopolysaccharidosis Type VI
Mucopolysaccharidosis Type IV
Mucopolysaccharidosis Type VII

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Longitudinal Studies of Brain Structure and Function in MPS Disorders

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Cognitive Ability (IQ) [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ Designated as safety issue: No ]
    Age-appropriate IQ tests will be administered at baseline and during subject's annual visit.


Secondary Outcome Measures:
  • Change in Quality of Life [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ 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 ] [ 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 ] [ 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 ] [ 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, diffusion tensor imaging (DTI), and resting state 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 ] [ 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.


Estimated Enrollment: 100
Study Start Date: September 2009
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
MPS IH, MPS IHS, MPS IS
MPS IH (Hurler syndrome) patients who are undergoing hematopoietic cell transplantation, or have had transplant in the past; MPS IHS (Hurler-Scheie syndrome) patients who are undergoing enzyme replacement therapy; MPS IS (Scheie syndrome) patients who are undergoing enzyme replacement therapy
MPS II
MPS II (Hunter syndrome) patients who are undergoing enzyme replacement therapy
MPS IV
MPS IV (Morquio syndrome) patients who will be considered for enrollment in the study on an individual basis
MPS VI
MPS VI (Maroteaux-Lamy syndrome) patients who have either had hematopoietic cell transplant, or are undergoing enzyme replacement therapy
MPS VII
MPS VII (Sly syndrome) patients who will be considered for enrollment in the study on an individual basis

Detailed Description:

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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  Eligibility

Ages Eligible for Study:   6 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients who have a verified diagnosis of MPS I, II, IV, VI or VII, aged 6-25 years.

Criteria

Inclusion Criteria:

  • Any MPS I, II, IV, VI or VII child or adult aged 6-25 years
  • Must be able to undergo neuropsychological testing and MRI examination

Exclusion Criteria:

  • Exclusion Criteria for Neuroimaging:

    • Participants with:

      • Pacemakers
      • Any indwelling electronic device including programmable shunts
      • Orthodontic braces unless they are not made of metal
      • Other implanted metal in the body other than titanium
      • Unable to stay still during MRI because of low cognitive function, behavioral dysregulation, or young age, if the patient is not a clinical patient having sedation/anesthesia
      • Pregnancy
  • Exclusion Criteria for Neuropsychological and Neurobehavioral Testing

    • Participants who:

      • Are too functionally impaired for testing
  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: NCT01870375

Contacts
Contact: Ashley Wiesenburger 612-301-1371 amwiesen@umn.edu

Locations
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@ucsf.edu   
Principal Investigator: Morton J. Cowan, M.D.         
L.A. BioMed at Harbor-UCLA Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Lynda E. Polgreen, M.D., M.S.    310-222-1972    lpolgreen@labiomed.org   
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30033
Contact: Stephanie Cagle, M.S.    404-778-8421    stephanie.cagle@emoryhealthycare.org   
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: Swapnil Parmar    212-263-6628    swapnil.parmar@nyumc.org   
Principal Investigator: Heather Lau, M.D.         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Mohammed Hussain    416-813-7654 ext 2646    mohammed.hussain@sickkids.ca   
Principal Investigator: Julian Raiman, M.D.         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Chester B. Whitley, M.D., Ph.D. University of Minnesota - Clinical and Translational Science Institute
Study Director: Ashley Wiesenburger 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
Study Chair: Lynda E. Polgreen, M.D., M.S. L.A. BioMed at Harbor-UCLA Medical Center
  More Information

Additional Information:
Publications:

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01870375     History of Changes
Other Study ID Numbers: 0905M65804, U54NS065768
Study First Received: August 2, 2011
Last Updated: July 24, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Mucopolysaccharidosis
Mucopolysaccharidosis type I
Mucopolysaccharidosis type II
Mucopolysaccharidosis type VI
Mucopolysaccharidosis type IV
Mucopolysaccharidosis type VII
Longitudinal
Brain
Cognition
Quality-of-Life
Hurler syndrome
Hunter syndrome
Hurler-Scheie syndrome
Scheie syndrome
Maroteaux-Lamy syndrome
MPS I
MPS II
MPS VI
MPS IV
MPS VII
Morquio syndrome
Sly syndrome

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI
Mucopolysaccharidosis VII
Osteochondrodysplasias
Bone Diseases
Bone Diseases, Developmental
Carbohydrate Metabolism, Inborn Errors
Connective Tissue Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Lysosomal Storage Diseases
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Mucinoses
Musculoskeletal Diseases
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations

ClinicalTrials.gov processed this record on July 28, 2015