Longitudinal Studies of Brain Structure and Function in MPS Disorders

Completed

• Conditions: Mucopolysaccharidosis Type I; Mucopolysaccharidosis Type VI; Mucopolysaccharidosis Type IV; Mucopolysaccharidosis Type VII; Mucopolysaccharidosis Type II

• Registration Number: NCT01870375
• Lead Sponsor: University of Minnesota

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2011-08-02
• Study First Submitted QC: 2013-06-03
• Study First Posted: 2013-06-06
• Primary Completion: 2019-08-31
• Study Completion: 2019-08-31
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-04
• Last Update Posted: 2019-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Cognitive Ability (IQ)	Baseline, Year 1, Year 2, Year 3	Age-appropriate IQ tests will be administered at baseline and during subject's annual visit.

Secondary Outcome Measures

Name	Time	Method
Change in Quality of Life	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 Emotional and Behavioral Health	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	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 Neuropsychological Status	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 Adaptive Functions	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.

Trial Locations

Locations (4)

Oakland Children's Hospital; 🇺🇸 Oakland, California, United States

Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

New York University; 🇺🇸 New York, New York, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States