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Longitudinal Studies of Brain Structure and Function in MPS Disorders

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ClinicalTrials.gov Identifier: NCT01870375
Recruitment Status : Recruiting
First Posted : June 6, 2013
Last Update Posted : December 13, 2018
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
National Center for Advancing Translational Science (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Lysosomal Disease Network
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Tracking Information
First Submitted Date August 2, 2011
First Posted Date June 6, 2013
Last Update Posted Date December 13, 2018
Actual Study Start Date September 2009
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 24, 2015)
Change in Cognitive Ability (IQ) [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
Age-appropriate IQ tests will be administered at baseline and during subject's annual visit.
Original Primary Outcome Measures
 (submitted: June 3, 2013)
Change in Cognitive Ability (IQ) [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ]
Age-appropriate IQ tests will be administered at baseline and during subject's annual visit.
Change History Complete list of historical versions of study NCT01870375 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 24, 2015)
  • Change in Quality of Life [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures
 (submitted: June 3, 2013)
  • Change in Quality of Life [ Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Longitudinal Studies of Brain Structure and Function in MPS Disorders
Official Title Longitudinal Studies of Brain Structure and Function in MPS Disorders
Brief Summary 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.
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population The study population is comprised of patients who have a verified diagnosis of MPS I, II, IV, VI or VII, aged 6 years of age or older.
Condition
  • Mucopolysaccharidosis Type I
  • Mucopolysaccharidosis Type II
  • Mucopolysaccharidosis Type VI
  • Mucopolysaccharidosis Type IV
  • Mucopolysaccharidosis Type VII
Intervention Not Provided
Study Groups/Cohorts
  • MPS IH, MPS IHS, MPS IS
    MPS IH (Hurler syndrome) patients; MPS IHS (Hurler-Scheie syndrome) patients; and MPS IS (Scheie syndrome) patients
  • MPS II
    Hunter syndrome patients
  • MPS IV
    Morquio syndrome patients who will be considered for enrollment in the study on an individual basis
  • MPS VI
    Maroteaux-Lamy syndrome patients
  • MPS VII
    Sly syndrome patients who will be considered for enrollment in the study on an individual basis
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 24, 2015)
100
Original Estimated Enrollment
 (submitted: June 3, 2013)
125
Estimated Study Completion Date August 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Any MPS I, II, IV, VI or VII child or adult aged 6 years of age or older

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
Sex/Gender
Sexes Eligible for Study: All
Ages 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Ashley Schneider 612-301-1371 amwiesen@umn.edu
Listed Location Countries Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01870375
Other Study ID Numbers 0905M65804
U54NS065768 ( U.S. NIH Grant/Contract )
0905M65804 ( Other Identifier: Univ. of Minnesota IRB Identifier Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: The study's data will be input to the Data Management and Coordinating Center ("DMCC"), which is a part of the NIH-funded Rare Diseases Clinical Research Network. Eventually the data will be available to researchers on the database of Genotypes and Phenotypes ("dbGaP"), a part of National Center for Biotechnology Information, U.S. National Library of Medicine.
Responsible Party University of Minnesota - Clinical and Translational Science Institute
Study Sponsor University of Minnesota - Clinical and Translational Science Institute
Collaborators
  • Rare Diseases Clinical Research Network
  • National Center for Advancing Translational Science (NCATS)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Lysosomal Disease Network
Investigators
Principal Investigator: Chester B. Whitley, M.D., Ph.D. University of Minnesota - Clinical and Translational Science Institute
Study Director: Ashley Schneider University of Minnesota - Clinical and Translational Science Institute
Study Chair: Paul Harmatz, M.D. Oakland Children's Hospital
Study Chair: Michal Inbar-Feigenberg, M.D. Hospital for Sick Children, Toronto, Ontario, CA
Study Chair: Heather Lau, M.D. New York University
PRS Account University of Minnesota - Clinical and Translational Science Institute
Verification Date December 2018