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Natural History Studies of Mucopolysaccharidosis III

This study has been completed.
Sanfilippo Children's Research Foundation
The Sanfilippo Research Foundation
The Children's Medical Research Foundation
Information provided by (Responsible Party):
Kevin Flanigan, Nationwide Children's Hospital Identifier:
First received: November 26, 2013
Last updated: November 12, 2015
Last verified: November 2015
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.

Condition Intervention
Mucopolysaccharidosis Type IIIA
Mucopolysaccharidosis Type IIIB
Procedure: Lumbar puncture
Device: Magnetic Resonance Imaging (MRI) of the brain

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Studies of Mucopolysaccharidosis III

Resource links provided by NLM:

Further study details as provided by Kevin Flanigan, Nationwide Children's Hospital:

Primary Outcome Measures:
  • Cognitive function [ Time Frame: up to 12 months ]
    Assessed using the Leiter International Performance assessment, a non-verbal assessment of cognitive function.

Secondary Outcome Measures:
  • Adaptive functioning [ Time Frame: Months 0, 6, and 12 ]
    Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System

  • Emotional/behavioral function [ Time Frame: Months 0, 6, and 12 ]
    Assessment of emotional/behavioral problems using the Child Behavioral Checklist

  • White and grey matter brain volumes [ Time Frame: Months 0 and 12 ]
    Assessment of brain volumes by MRI. MRI will be performed under sedation.

Other Outcome Measures:
  • Serum and cerebrospinal fluid NAGLU (MPSIIIB subjects) or SGSH (MPSIIIA subjects) levels [ Time Frame: Months 0 and 12 ]
    Measurement of NAGLU or SGSH activity in serum (by venipuncture) and CSF (by lumbar puncture). Lumbar puncture will be performed under sedation.

  • Liver size [ Time Frame: Months 0 and 12 ]
    Liver volume will be assessed by abdominal MRI obtained under the same sedation event as brain MRI and lumbar puncture.

Biospecimen Retention:   Samples With DNA

Biobanking will include:

  1. Serum/Plasma
  2. Cerebrospinal fluid

Enrollment: 25
Study Start Date: February 2014
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
MPS IIIA/B Subjects
Cohort will be followed for one year to assess natural history of the disease.
Procedure: Lumbar puncture Device: Magnetic Resonance Imaging (MRI) of the brain

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.


Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals affected by MPS IIIA or MPS IIIB will be considered for this study.

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT02037880

United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Nationwide Children's Hospital
Sanfilippo Children's Research Foundation
The Sanfilippo Research Foundation
The Children's Medical Research Foundation
Principal Investigator: Kevin M Flanigan, MD Nationwide Children's Hospital, Columbus, Ohio
  More Information

Responsible Party: Kevin Flanigan, MD, Nationwide Children's Hospital Identifier: NCT02037880     History of Changes
Other Study ID Numbers: MPSIII-1
Study First Received: November 26, 2013
Last Updated: November 12, 2015

Keywords provided by Kevin Flanigan, Nationwide Children's Hospital:

Additional relevant MeSH terms:
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases processed this record on May 25, 2017