Clinical trial NCT01870375: Longitudinal Studies of Brain Structure and Function in MPS Disorders
Official title: Longitudinal Studies of Brain Structure and Function in MPS Disorders
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mucopolysaccharidosis Type I
Mucopolysaccharidosis Type II
Mucopolysaccharidosis Type VI
Mucopolysaccharidosis Type IV
Mucopolysaccharidosis Type VII
Keywords: Mucopolysaccharidosis
Longitudinal
Brain
Cognition
Quality-of-Life
Hurler syndrome
Hunter syndrome
Hurler-Scheie syndrome
Scheie syndrome
Maroteaux-Lamy syndrome
MPS I
MPS II
MPS VI
Mucopolysaccharidosis type I
Mucopolysaccharidosis type II
Mucopolysaccharidosis type VI
MPS IV
MPS VII
Mucopolysaccharidosis type IV
Mucopolysaccharidosis type VII
Morquio syndrome
Sly syndrome
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: National Center for Advancing Translational Sciences (NCATS)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Lysosomal Disease Network
First posted: 2013-06-06
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Change in Cognitive Ability (IQ)
timeFrame: Baseline, Year 1, Year 2, Year 3
Secondary outcomes:
measure: Change in Quality of Life
timeFrame: Baseline, Year 1, Year 2, Year 3
measure: Change in Neuropsychological Status
timeFrame: Baseline, Year 1, Year 2, Year 3
measure: Change in Emotional and Behavioral Health
timeFrame: Baseline, Year 1, Year 2, Year 3
measure: Change Shown in Magnetic Resonance Imaging of the Brain
timeFrame: Baseline, Year 1, Year 2, Year 3
measure: Change in Adaptive Functions
timeFrame: Baseline, Year 1, Year 2, Year 3
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Oakland Children's Hospital
state: California
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: New York University
state: New York
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: University of Minnesota
name: Chester B. Whitley, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Ashley Schneider
role: STUDY_DIRECTOR
affiliation: Oakland Children's Hospital
name: Paul Harmatz, M.D.
role: STUDY_CHAIR
affiliation: Hospital for Sick Children, Toronto, Ontario, CA
name: Michal Inbar-Feigenberg, M.D.
role: STUDY_CHAIR
affiliation: New York University
name: Heather Lau, M.D.
role: STUDY_CHAIR
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