Natural History Studies of Mucopolysaccharidosis III

Mucopolysaccharidosis Type IIIB Clinical Trial

Official title:

Natural History Studies of Mucopolysaccharidosis III

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02037880
• Other study ID #: MPSIII-1
• Status: Completed
• Phase: N/A
• First received: November 26, 2013
• Last updated: November 12, 2015
• Start date: February 2014
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis III
• Mucopolysaccharidosis Type IIIA
• Mucopolysaccharidosis Type IIIB

Intervention

Procedure:
• Lumbar puncture

Device:
• Magnetic Resonance Imaging (MRI) of the brain

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
Nationwide Children's Hospital	Sanfilippo Children's Research Foundation, The Children's Medical Research Foundation, The Sanfilippo Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Primary	Cognitive function	Assessed using the Leiter International Performance assessment, a non-verbal assessment of cognitive function.	up to 12 months	No
Secondary	Adaptive functioning	Parental assessment of adaptive functioning using the Adaptive Behavioral Assessment System	Months 0, 6, and 12	No
Secondary	Emotional/behavioral function	Assessment of emotional/behavioral problems using the Child Behavioral Checklist	Months 0, 6, and 12	No
Secondary	White and grey matter brain volumes	Assessment of brain volumes by MRI. MRI will be performed under sedation.	Months 0 and 12	No