Natural History Studies of Mucopolysaccharidosis III

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.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis Type IIIA; Mucopolysaccharidosis Type IIIB
• Intervention / Treatment: 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.

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals affected by MPS IIIA or MPS IIIB will be considered for this study.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function	Assessed using the Leiter International Performance assessment, a non-verbal assessment of cognitive function.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adaptive functioning	Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System	Months 0, 6, and 12
Emotional/behavioral function	Assessment of emotional/behavioral problems using the Child Behavioral Checklist	Months 0, 6, and 12
White and grey matter brain volumes	Assessment of brain volumes by MRI. MRI will be performed under sedation.	Months 0 and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum and cerebrospinal fluid NAGLU (MPSIIIB subjects) or SGSH (MPSIIIA subjects) levels	Measurement of NAGLU or SGSH activity in serum (by venipuncture) and CSF (by lumbar puncture). Lumbar puncture will be performed under sedation.	Months 0 and 12
Liver size	Liver volume will be assessed by abdominal MRI obtained under the same sedation event as brain MRI and lumbar puncture.	Months 0 and 12

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Collaborators: Sanfilippo Children's Research Foundation; The Sanfilippo Research Foundation; The Children's Medical Research Foundation
• Investigators: Principal Investigator: Kevin M Flanigan, MD, Nationwide Children's Hospital, Columbus, Ohio

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): November 1, 2015
• Study Completion (ACTUAL): November 1, 2015

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (ESTIMATE): January 16, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): November 16, 2015
• Last Update Submitted That Met QC Criteria: November 12, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: MPS; Mucopolysaccharidosis; Sanfilippo
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis III
• Other Study ID Numbers: MPSIII-1