Natural History Studies of Mucopolysaccharidosis III

• Sponsor: Nationwide Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02037880
• Collaborator: Sanfilippo Children's Research Foundation (Other), The Sanfilippo Research Foundation (Other), The Children's Medical Research Foundation (Other)
• Enrollment: 25
• Location: 1
• Duration (Months): 21
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis Type IIIA; Mucopolysaccharidosis Type IIIB	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 Design

• Study Type: Observational
• Actual Enrollment: 25 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Natural History Studies of Mucopolysaccharidosis III
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Cognitive function [up to 12 months]

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

Secondary Outcome Measures

1. Adaptive functioning [Months 0, 6, and 12]

   Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System

2. Emotional/behavioral function [Months 0, 6, and 12]

   Assessment of emotional/behavioral problems using the Child Behavioral Checklist

3. White and grey matter brain volumes [Months 0 and 12]

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

Other Outcome Measures

1. Serum and cerebrospinal fluid NAGLU (MPSIIIB subjects) or SGSH (MPSIIIA subjects) levels [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.

2. Liver size [Months 0 and 12]

   Liver volume will be assessed by abdominal MRI obtained under the same sedation event as brain MRI and lumbar puncture.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 2 years old or greater

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

3. No detectable or significantly reduced NAGLU (MPSIIIB) or SGSH (MPSIIIA) activity in serum or leukocyte assay

4. Genomic DNA mutation analysis demonstrating a homozygous or compound heterozygous mutations in the NAGLU (MPSIIIB) or SGSH (MPSIIIA) genes

5. 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

Locations

	Site	City	State	Country	Postal Code
1	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

Investigators

• Principal Investigator: Kevin M Flanigan, MD, Nationwide Children's Hospital, Columbus, Ohio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kevin Flanigan, MD, Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT02037880
• Other Study ID Numbers: MPSIII-1
• First Posted: Jan 16, 2014
• Last Update Posted: Nov 16, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Kevin Flanigan, MD, Nationwide Children's Hospital: Mucopolysaccharidosis; MPS; Sanfilippo
• Additional relevant MeSH terms: Mucopolysaccharidoses; Mucopolysaccharidosis III

Study Results

No Results Posted as of Nov 16, 2015