Longitudinal Studies of Brain Structure and Function in MPS Disorders

September 4, 2019 updated by: University of Minnesota
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.

Study Overview

Status

Completed

Conditions

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

Enrollment (Actual)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1X8
        • Hospital for Sick Children
  • United States
    • California
      • Oakland, California, United States, 94609
        • Oakland Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • New York
      • New York, New York, United States, 10016
        • New York University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Year 1, Year 2, Year 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Year 1, Year 2, Year 3
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.
Baseline, Year 1, Year 2, Year 3
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.
Baseline, Year 1, Year 2, Year 3
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.
Baseline, Year 1, Year 2, Year 3
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.
Baseline, Year 1, Year 2, Year 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Neurological Disorders and Stroke (NINDS)
Rare Diseases Clinical Research Network
National Center for Advancing Translational Sciences (NCATS)
Lysosomal Disease Network

Investigators

  • Principal Investigator: Chester B. Whitley, M.D., Ph.D., University of Minnesota
  • Study Director: Ashley Schneider, University of Minnesota
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2009

Primary Completion (ACTUAL)

August 31, 2019

Study Completion (ACTUAL)

August 31, 2019

Study Registration Dates

First Submitted

August 2, 2011

First Submitted That Met QC Criteria

June 3, 2013

First Posted (ESTIMATE)

June 6, 2013

Study Record Updates

Last Update Posted (ACTUAL)

September 6, 2019

Last Update Submitted That Met QC Criteria

September 4, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0905M65804 (OTHER: Univ. of Minnesota IRB Identifier Number)
  • U54NS065768 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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