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Natural History Studies of Mucopolysaccharidosis III

Completed
Conditions
Mucopolysaccharidosis Type IIIA
Mucopolysaccharidosis Type IIIB
Interventions
Procedure: Lumbar puncture
Device: Magnetic Resonance Imaging (MRI) of the brain
Registration Number
NCT02037880
Lead Sponsor
Nationwide Children's Hospital
Brief Summary

The purpose of this study is to assess rates of decline in motor and cognitive functional measures, and to assess potential biomarkers, in order to identify potential outcome measure appropriate for use in therapeutic clinical trials.

Detailed Description

Mucopolysaccharidosis (MPS) type III (Sanfilippo syndrome) is a group of four devastating genetic diseases that result in the abnormal accumulation of glycosaminoglycans in body tissues. In MPSIII the predominant symptoms occur due to accumulation within the central nervous system (CNS), including the brain and spinal cord, resulting in cognitive decline, motor dysfunction, and eventual death.

In anticipation for future therapeutic studies for MPSIIIA and MPSIIIB, we are performing a natural history study to identify the following:

1. Individual rates of decline in motor and cognitive function in a cohort of potential clinical trial patients

2. The natural history of outcome measures in order to assess their appropriateness as outcomes in an eventual trial

3. Baseline functional data in patients who will be potential candidates for an eventual trial

4. Biomarkers of disease progression over a 12-month interval, including changes in brain MRI and in cerebrospinal fluid

Patients in this study will need to come to Nationwide Children's Hospital in Columbus, Ohio, three times. At each of these three time points, cognitive outcome measures will be assessed: at baseline (visit 1), 6 months (visit 2), and at 12 months (visit 3). At baseline (visit 1) and 12 months (visit 3), an MRI and a lumbar puncture will be performed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
Inclusion Criteria
  1. Age 2 years old or greater

  2. Confirmed diagnosis of MPSIIIA or MPSIIIB by either of two methods:

    1. No detectable or significantly reduced NAGLU (MPSIIIB) or SGSH (MPSIIIA) activity in serum or leukocyte assay
    2. Genomic DNA mutation analysis demonstrating a homozygous or compound heterozygous mutations in the NAGLU (MPSIIIB) or SGSH (MPSIIIA) genes
  3. Clinical history of or examination features of neurologic dysfunction.

Exclusion Criteria
  1. Inability to participate in the clinical evaluations
  2. Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
  3. Inability to be safely sedated in the opinion of the clinical anesthesiologist

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
MPS IIIA/B SubjectsMagnetic Resonance Imaging (MRI) of the brainCohort will be followed for one year to assess natural history of the disease.
MPS IIIA/B SubjectsLumbar punctureCohort will be followed for one year to assess natural history of the disease.
Primary Outcome Measures
NameTimeMethod
Cognitive functionup to 12 months

Assessed using the Leiter International Performance assessment, a non-verbal assessment of cognitive function.

Secondary Outcome Measures
NameTimeMethod
Adaptive functioningMonths 0, 6, and 12

Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System

Emotional/behavioral functionMonths 0, 6, and 12

Assessment of emotional/behavioral problems using the Child Behavioral Checklist

White and grey matter brain volumesMonths 0 and 12

Assessment of brain volumes by MRI. MRI will be performed under sedation.

Trial Locations

Locations (1)

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

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