- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01873911
Neurobehavioral Phenotypes in MPS III
Characterizing the Neurobehavioral Phenotype(s) in MPS III
Hypothesis #1: Factor analysis of the revised Sanfilippo Behavior Rating Scale (SBRS) will identify a group of externalizing behaviors and a group of Klüver-Bucy syndrome-like behaviors as two different factors that are at least partially independent.
Hypothesis #2a: Children with MPS III will show more hyperlocomotion, fearlessness, asociality and noncompliance than children of similar cognitive ability with MPS I.
Hypothesis #2b: These behaviors will become more frequent and/or intensify over time, consistent with the Cleary and Wraith (1993) model. Quantifying them will provide a more empirical framework for staging disease progression.
Hypothesis #3: Brain volumetric analysis and diffusion-tensor imaging will reveal abnormalities of frontal and temporal lobe structures that will correlate with externalizing and Klüver-Bucy syndrome-like behaviors, respectively.
Hypothesis #4. Loss of cognitive and language function as measures of neurologic decline will directly precede or co-vary with behavioral decline.
The primary objective of this study is to identify the behavioral phenotype and its neural basis in MPS III (Sanfilippo syndrome). Is the behavioral phenotype similar to that of Klüver-Bucy syndrome, and is there evidence for amygdala abnormality? The secondary objective of this research study is to develop easily administered, sensitive and specific neurobehavioral and neuroimaging markers to characterize the behavioral phenotype(s) of MPS III; to track their progression; and to delineate their neural substrates. Such markers are critical for identifying the stage of disease for each patient, and to measure treatment outcome. Although we know that severe cognitive decline is one essential characteristic of MPS III, the other highly salient characteristic is a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. These behaviors set Sanfilippo syndrome apart from the other MPS disorders. They cause major disruption in the child's familial, school, and community environments. Delineating these behavioral abnormalities will help in better understanding the neurological disease.
Study Overview
Status
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Research Subjects: Verified diagnosis of MPS IIIA or MPS IIIB (having proof of either genetic mutation or enzymatic analysis prior to enrollment in this study); must be between the ages of 2 and 12 years; must be able to walk.
Control group: Verified diagnosis of MPS IH; must have already undergone hematopoietic cell transplantation in the past; must be aged between 2 and 5 years; and must be able to walk without support.
Exclusion Criteria:
Participants will be excluded who are unable to cooperate or comply with this study's procedures; in the opinion of the principal investigator, participants who have other severely-limiting co-existing conditions such as severe hearing or visual impairment, will be excluded from this study.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Assessment of Temperament
Time Frame: Within One Year of Enrollment
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Using Risk Room procedures of the established "Laboratory Temperament Assessment Battery" (Lab-TAB), the investigators will measure and record each subject's startle, exploration (fear), compliance, and attachment.
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Within One Year of Enrollment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life Measures
Time Frame: Within One Year of Enrollment
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Assessments of research subjects' quality of life will be made using age-appropriate standardized assessment tools.
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Within One Year of Enrollment
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Event-Related Potentials Measurement
Time Frame: Within One Year of Enrollment
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High-density Event-Related Potentials (ERPs) will be elicited and recorded.
ERPs provide information about the timing and location of neurocognitive processes associated with the individual's processing of discrete stimuli.
Two sets of stimuli will be used: 1. auditory stimuli consisting of non-language sounds and phonemes; and 2. visual stimuli consisting of images of emotional faces.
All stimuli will be presented in an oddball paradigm format (repetition of stimuli with a random insertion of a novel stimulus).
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Within One Year of Enrollment
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Magnetic Resonance Imaging Examination
Time Frame: Within One Year of Enrollment
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To examine the neural substrate of MPS III behavioral phenotypes of participating research subjects, the investigators will perform high-resolution brain volumetric magnetic resonance imaging (MRI) during clinical scans.
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Within One Year of Enrollment
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Assessment of Cognitive Development
Time Frame: Within One Year of Enrollment
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Research subjects' cognitive development will be assessed using age-appropriate standardized assessment tools.
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Within One Year of Enrollment
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Elsa G Shapiro, PhD, University of Minnesota
- Principal Investigator: Michael Potegal, PhD, University of Minnesota
Publications and helpful links
General Publications
- Cleary MA, Wraith JE. Management of mucopolysaccharidosis type III. Arch Dis Child. 1993 Sep;69(3):403-6. doi: 10.1136/adc.69.3.403. No abstract available.
- Meyer A, Kossow K, Gal A, Muhlhausen C, Ullrich K, Braulke T, Muschol N. Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics. 2007 Nov;120(5):e1255-61. doi: 10.1542/peds.2007-0282. Epub 2007 Oct 15.
- Jha S, Patel R. Kluver-Bucy syndrome -- an experience with six cases. Neurol India. 2004 Sep;52(3):369-71.
- Angrilli A, Mauri A, Palomba D, Flor H, Birbaumer N, Sartori G, di Paola F. Startle reflex and emotion modulation impairment after a right amygdala lesion. Brain. 1996 Dec;119 ( Pt 6):1991-2000. doi: 10.1093/brain/119.6.1991.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0806M35341
- U54NS065768 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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