Longitudinal Studies of Brain Structure and Function in MPS Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 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: April 21, 2014
Last verified: April 2014
  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

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, Year 4 ] [ 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, Year 4 ] [ 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, Year 4 ] [ 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, Year 4 ] [ 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, Year 4 ] [ 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 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 ] [ 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: 125
Study Start Date: September 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
MPS I H (Hurler syndrome)
MPS IH (Hurler syndrome) patients who are undergoing transplantation or have had transplant in the past.
MPS I Attenuated
Patients diagnosed with either Hurler Scheie or Scheie syndrome on Enzyme Replacement Therapy (ERT)
MPS II
Patients with Hunter syndrome who are on Enzyme Replacement Therapy
MPS VI
Patients with Maroteaux-Lamy syndrome who have either had hematopoietic cell transplant or are on enzyme replacement therapy

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients who have verified diagnosis of MPS I, II, or VI. There are no age limitations.

Criteria

Inclusion Criteria:

  • Diagnosis of MPS I, II, or VI
  • Must be able to undergo neuropsychological testing and MRI

Exclusion Criteria:

  • Dental braces or other implanted metal that are not safe for MRI scan
  • pacemakers unless documented to be MRI safe
  • behavioral abnormalities precluding cooperation
  • pregnancy
  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

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@ucsfmedctr.org   
Contact: Jueleah         
Principal Investigator: Morton J. Cowan, M.D.         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30033
Contact: Stephanie Cagle, MS    404-778-8421    scagle@emory.edu   
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: Marissa Ferraris    212-263-0139    Marissa.Ferraris@nyumc.org   
Principal Investigator: Heather Lau, M.D.         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Margaret Macrell, RN    416-813-8367    margaret.mackrell@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: Elsa G. Shapiro, Ph.D. University of Minnesota - Clinical and Translational Science Institute
Study Director: Kathleen Delaney 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
  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: April 21, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis VI
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
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations

ClinicalTrials.gov processed this record on October 21, 2014