Sanfilippo Syndrome Type ANCT01873911
Neurobehavioral Phenotypes in MPS III
An observational study of Sanfilippo Syndrome Type A and Sanfilippo Syndrome Type B, run by University of Minnesota at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Sanfilippo Syndrome Type A, Sanfilippo Syndrome Type B, Hurler Syndrome
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Aug 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Study population: Twenty children who have been diagnosed with MPS III type A or type B. Ten age-matched children (as controls) who have been diagnosed with MPS I (Hurler syndrome), who in the past have undergone hematopoietic cell transplantation, and who have been clinically-determined to have low cognitive function.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: 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.
Read more
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.
Read the detailed description
Like some other mucopolysaccharidosis (MPS) syndromes, MPS III (Sanfilippo syndrome) is characterized by a severe cognitive decline ending in dementia and death. Unlike other MPS syndromes, earlier-stage MPS III is also associated with a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. These behaviors, which cause major disruption in the child's familial, school, and community environments, set MPS III apart from the other MPS disorders. These behaviors may also indicate the identity of the neural pathways affected in this disease; their sequence of onsets may indicate the order in which these pathways are affected. We propose to define and categorize the behavioral profile(s) or phenotype(s) of MPS III and correlate them with clinical quantitative neuroimaging in order to understand the neural bases of the disease. In addition, we will use these results to develop a set of sensitive and specific measures that can be easily administered by health care professionals to help monitor the disease and the efficacy of future treatments.
- Keywords
- MPS IIIA, MPS IIIB, Sanfilippo syndrome type A, Sanfilippo syndrome type B, Hurler syndrome, cognitive decline, MPS IH
- Medical subject headings
- Mucopolysaccharidosis III, Mucopolysaccharidosis I, Cognitive Dysfunction
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Temperament
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.
Measured: Within One Year of Enrollment
Secondary outcomes (4)
Quality of Life Measures
Assessments of research subjects' quality of life will be made using age-appropriate standardized assessment tools.
Measured: Within One Year of Enrollment
Event-Related Potentials Measurement
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).
Measured: Within One Year of Enrollment
Magnetic Resonance Imaging Examination
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.
Measured: Within One Year of Enrollment
Assessment of Cognitive Development
Research subjects' cognitive development will be assessed using age-appropriate standardized assessment tools.
Measured: Within One Year of Enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2013 (estimated)
- Study startDec 2010
- Primary completionJul 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sanfilippo Syndrome Type AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National MPS Society, Shire Human Genetic Therapies, Inc.
- Responsible party
- Sponsor
- Investigators
- Elsa G Shapiro, PhD, Principal investigator, University of MinnesotaMichael Potegal, PhD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01873911
- Sponsor's protocol ID
- 0806M35341
- Other IDs
- U54NS065768
- Status last verified
- Oct 2019
- First submitted
- 28 May 2013
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 8215557Meyer 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.
PubMed 17938166Jha S, Patel R. Kluver-Bucy syndrome -- an experience with six cases. Neurol India. 2004 Sep;52(3):369-71.
PubMed 15472430Angrilli 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.
PubMed 9010003
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing the Neurobehavioral Phenotype(s) in MPS III
- ClinicalTrials.gov ID
- NCT01873911
- Acronym / sponsor ID
- 0806M35341
- Keywords
- MPS IIIA, MPS IIIB, Sanfilippo syndrome type A, Sanfilippo syndrome type B, Hurler syndrome, cognitive decline, MPS IH
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National MPS Society, Shire Human Genetic Therapies, Inc.
- Study start
- Dec 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 10 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Like some other mucopolysaccharidosis (MPS) syndromes, MPS III (Sanfilippo syndrome) is characterized by a severe cognitive decline ending in dementia and death. Unlike other MPS syndromes, earlier-stage MPS III is also associated with a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. These behaviors, which cause major disruption in the child's familial, school, and community environments, set MPS III apart from the other MPS disorders. These behaviors may also indicate the identity of the neural pathways affected in this disease; their sequence of onsets may indicate the order in which these pathways are affected. We propose to define and categorize the behavioral profile(s) or phenotype(s) of MPS III and correlate them with clinical quantitative neuroimaging in order to understand the neural bases of the disease. In addition, we will use these results to develop a set of sensitive and specific measures that can be easily administered by health care professionals to help monitor the disease and the efficacy of future treatments.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Twenty children who have been diagnosed with MPS III type A or type B. Ten age-matched children (as controls) who have been diagnosed with MPS I (Hurler syndrome), who in the past have undergone hematopoietic cell transplantation, and who have been clinically-determined to have low cognitive function.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of Temperament
Time frame: Within One Year of Enrollment
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.
4 secondary outcomes
Quality of Life Measures
Time frame: Within One Year of Enrollment
Event-Related Potentials Measurement
Time frame: Within One Year of Enrollment
Magnetic Resonance Imaging Examination
Time frame: Within One Year of Enrollment
Assessment of Cognitive Development
Time frame: Within One Year of Enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Background: PubMed 8215557Cleary 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.
- Background: PubMed 17938166Meyer 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.
- Background: PubMed 15472430Jha S, Patel R. Kluver-Bucy syndrome -- an experience with six cases. Neurol India. 2004 Sep;52(3):369-71.
- Background: PubMed 9010003Angrilli 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.
- National MPS SocietyLink provided by the sponsor.
Related trials for Sanfilippo Syndrome Type A
Active, not recruitingPhase 1
Phase 1 Study of GC1130A in Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo Syndrome Type A
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Natural History to Assess Disease in Patients With MPS IIIC
Sanfilippo Syndrome Type C, Mucopolysaccharidosis (MPS) IIIC
RecruitingObservational study
Natural History Study of Participants With Sanfilippo Syndrome Type IIIC
Sanfilippo Syndrome Type C
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elsa G Shapiro, PhD principal investigator
University of Minnesota
Michael Potegal, PhD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sanfilippo Syndrome Type A and Sanfilippo Syndrome Type B, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Temperament (time frame: Within One Year of Enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01873911, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019; AzTrials last refreshed its copy on 27 Oct 2026.