Carotid Structure and Function in MPS Syndromes: A Multicenter Study of the Lysosomal Disease Network

Sponsor
University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT01586871
Collaborator
Rare Diseases Clinical Research Network (Other), National Center for Advancing Translational Science (NCATS) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
1,147
Enrollment
2
Locations
63
Duration (Months)
573.5
Patients Per Site
9.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Mucopolysaccharidosis (MPS) syndromes are disorders characterized by enzyme deficiencies, and they have been linked to heart health complications. However, there are currently no proven markers of heart and artery health for this population. The main purpose of this observational study is to evaluate the ease and convenience of a non-invasive measurement of artery function in MPS I, MPS II and MPS VI patients compared to healthy control subjects. An observational study is a research design meaning that there is no treatment in this study.

The research questions are:
  1. Is the artery health of MPS I, II and VI patients different than healthy controls?

  2. Is the artery health of MPS VI patients different than MPS I and II patients?

It is hypothesized that MPS patients will have poorer outcomes of artery health compared to healthy controls.

Condition or DiseaseIntervention/TreatmentPhase

    Detailed Description

    Mucopolysaccharidosis (MPS) syndromes are disorders characterized by enzyme deficiencies. As a result of the enzyme deficiency, glycosaminoglycans that are normally recycled in a healthy individual cannot be degraded in the MPS patient. MPS syndromes have been linked to heart health complications. Complications related to coronary artery stenosis (narrowing) are recognized as potentially fatal sequelae of untreated and treated MPS. Presently, national guidelines are largely silent on coronary artery disease risk in this population. There are currently no validated markers of cardiovascular or coronary artery disease in the MPS population. The main purpose of this observational study is to evaluate the ease and convenience of a non-invasive measurement of artery function in MPS I, MPS II and MPS VI patients compared to healthy control subjects. Exploring the validity and usefulness of this non-invasive measurement is the first step towards developing validated markers of cardiovascular or coronary artery disease in the MPS population.

    Specific Aim #1: Compare carotid artery intima-media thickness and carotid stiffness in individuals with MPS I, II, and VI (treated and non-treated) vs. healthy age-and gender-matched controls. It is hypothesized that MPS patients will have increased carotid artery thickness and reduced carotid compliance and distensibility compared to healthy controls.

    Specific Aim #2: Compare carotid artery intima-media thickness and carotid stiffness in individuals with MPS VI vs. I and II and between MPS I patients clinically treated with HSCT vs. ERT. It is hypothesized that MPS VI will have decreased carotid thickness and increased carotid compliance and distensibility compared to MPS I and II and that MPS I patients treated with ERT will have increased carotid thickness and reduced carotid compliance and distensibility compared to MPS I patients treated with HSCT.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    1147 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Retrospective
    Official Title:
    Carotid Structure and Function in MPS Syndromes: A Multicenter Study of the Lysosomal Disease Network
    Study Start Date :
    Mar 1, 2012
    Actual Primary Completion Date :
    Aug 1, 2016
    Actual Study Completion Date :
    Jun 1, 2017

    Outcome Measures

    Primary Outcome Measures

    1. Carotid Intima-media Thickness, Measured in Millimeters [Baseline]

      The carotid intima-media thickness test (CIMT) is a measure used to diagnose the extent of carotid atherosclerotic vascular disease. The test measures the thickness of the inner two layers of the carotid artery-the intima and media-and alerts physicians to any thickening when patients are still asymptomatic. CIMT was measured from the far wall of the left common carotid.

    Secondary Outcome Measures

    1. Carotid Cross-sectional Distensibility [Baseline]

      Carotid distensibility is a measure of carotid artery elasticity that has been introduced as a risk factor for cardiovascular disease. It is defined by the percent change in carotid lumen area from diastole to systole, has the unit of % and is defined by the equation (sD^2 - dD^2/dD^2)*100 where sD is the maximum systolic carotid diameter, dD is the minimum diastolic carotid diameter. Increasing carotid distensibility reflects high carotid distensibility and low stiffness, and vice versa.

    2. Carotid Cross-sectional Compliance [Baseline]

      This is defined by the relative change in carotid lumen area from diastole to systole for a given change in blood pressure, has the unit mm^2/mmHg and is defined by the equation ¶(sD^2-dD^2)/4*PP where PP is pulse pressure (or systolic blood pressure-diastolic blood pressure). Increasing carotid cross sectional compliance reflects high carotid distensibility and low stiffness, and vice versa.

    3. Carotid Incremental Elastic Modulus [Baseline]

      A way of measuring the elasticity constant of the carotid vessel, has the unit mmHg and is defined by the equation 3(1+sD^2/dD^2)/cross sectional compliance value. In contrast to carotid cross sectional compliance and carotid cross sectional distensibility, increasing carotid incremental elastic modus reflects low carotid distensibility and high thickness.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Years to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Be between the ages of 3 and 18 years old

    • Be diagnosed with MPS I, MPS II or MPS VI

    Exclusion Criteria:
    • None

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Children's Hospital of Orange CountyOrangeCaliforniaUnited States92868
    2University of MinnesotaMinneapolisMinnesotaUnited States55455

    Sponsors and Collaborators

    • University of Minnesota
    • Rare Diseases Clinical Research Network
    • National Center for Advancing Translational Science (NCATS)
    • National Institute of Neurological Disorders and Stroke (NINDS)
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Investigators

    • Principal Investigator: Aaron S Kelly, Ph.D., University of Minnesota

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT01586871
    Other Study ID Numbers:
    • 1202M09721
    • U54NS065768
    First Posted:
    Apr 27, 2012
    Last Update Posted:
    Feb 24, 2021
    Last Verified:
    Feb 1, 2021
    Keywords provided by University of Minnesota
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThis was a dual-center, cross-sectional assessment of carotid imaging data obtained from 33 patients with biochemically and/or molecularly confirmed MPS Types I, II, III and VI; 560 healthy pediatric control patients; and 554 adult control patients. The pediatric and adult controls were obtained from prior studies of insulin resistance and cardiovascular risk at the University of Minnesota. Clinical data from MPS patients were obtained from chart review.
    Pre-assignment Detail
    Arm/Group TitlePediatric Control PatientsAdult ControlsMPS Patients
    Arm/Group DescriptionThe pediatric control patients were obtained from prior studies of insulin resistance and cardiovascular risk at the University of Minnesota.The adult controls were obtained from prior studies of insulin resistance and cardiovascular risk at the University of Minnesota.Clinical data (demographic information, anthropometrics, ethnicity, confirmation of diagnosis, and treatment status) from MPS patients were obtained from chart review. For this project, data from MPS I, MPS II, MPS IIIa and MPS VI was available.
    Period Title: Overall Study
    STARTED56055433
    COMPLETED56055433
    NOT COMPLETED000

    Baseline Characteristics

    Arm/Group TitlePediatric ControlAdult ControlMucopolysaccharidosis (MPS ) SubjectsTotal
    Arm/Group DescriptionHealthy pediatric control subjectsHealthy adult control subjectsMucopolysaccharidosis subjects type I, II, IIIA and VI.Total of all reporting groups
    Overall Participants560554331147
    Age (years) [Median (Standard Deviation) ]
    Median (Standard Deviation) [years]
    13.14
    (4.01)
    39.16
    (2.24)
    12.47
    (4.66)
    21.59
    (3.63)
    Sex: Female, Male (Count of Participants)
    Female
    259
    46.3%
    285
    51.4%
    10
    30.3%
    554
    48.3%
    Male
    301
    53.8%
    269
    48.6%
    23
    69.7%
    593
    51.7%
    Height (centimeters) [Median (Standard Deviation) ]
    Median (Standard Deviation) [centimeters]
    155
    (18.3)
    171
    (12.8)
    132
    (16.59)
    152.66
    (15.89)
    Weight (kilograms) [Median (Standard Deviation) ]
    Median (Standard Deviation) [kilograms]
    53.8
    (23.54)
    86.39
    (23.33)
    36.66
    (16.74)
    58.95
    (21.20)
    Body Mass Index (Kg/m^2) [Median (Standard Deviation) ]
    Median (Standard Deviation) [Kg/m^2]
    21.44
    (5.84)
    29.46
    (7.47)
    20.03
    (4.50)
    23.64
    (5.93)
    Systolic blood pressure (mm Hg) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mm Hg]
    106
    (10.42)
    125
    (15.59)
    106
    (10.98)
    112.33
    (12.33)
    Diastolic blood pressure (mm Hg) [Median (Standard Deviation) ]
    Median (Standard Deviation) [mm Hg]
    58
    (7.78)
    71.97
    (10.39)
    55
    (13.73)
    61.65
    (10.63)

    Outcome Measures

    1. Primary Outcome
    TitleCarotid Intima-media Thickness, Measured in Millimeters
    DescriptionThe carotid intima-media thickness test (CIMT) is a measure used to diagnose the extent of carotid atherosclerotic vascular disease. The test measures the thickness of the inner two layers of the carotid artery-the intima and media-and alerts physicians to any thickening when patients are still asymptomatic. CIMT was measured from the far wall of the left common carotid.
    Time FrameBaseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePediatric ControlAdult ControlMucopolysaccharidosis (MPS ) Subjects
    Arm/Group DescriptionHealthy pediatric control subjectsHealthy adult control subjectsMucopolysaccharidosis subjects type I, II, IIIA and VI.
    Measure Participants56055433
    Median (Standard Deviation) [mm]
    0.44
    (0.04)
    0.52
    (0.09)
    0.56
    (0.05)
    2. Secondary Outcome
    TitleCarotid Cross-sectional Distensibility
    DescriptionCarotid distensibility is a measure of carotid artery elasticity that has been introduced as a risk factor for cardiovascular disease. It is defined by the percent change in carotid lumen area from diastole to systole, has the unit of % and is defined by the equation (sD^2 - dD^2/dD^2)*100 where sD is the maximum systolic carotid diameter, dD is the minimum diastolic carotid diameter. Increasing carotid distensibility reflects high carotid distensibility and low stiffness, and vice versa.
    Time FrameBaseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePediatric ControlAdult ControlMucopolysaccharidosis (MPS ) Subjects
    Arm/Group DescriptionHealthy pediatric control subjectsHealthy adult control subjectsMucopolysaccharidosis subjects type I, II, IIIA and VI.
    Measure Participants56055433
    Mean (Standard Deviation) [percentage of change]
    32.03
    (8.35)
    16.33
    (4.73)
    28.36
    (15.70)
    3. Secondary Outcome
    TitleCarotid Cross-sectional Compliance
    DescriptionThis is defined by the relative change in carotid lumen area from diastole to systole for a given change in blood pressure, has the unit mm^2/mmHg and is defined by the equation ¶(sD^2-dD^2)/4*PP where PP is pulse pressure (or systolic blood pressure-diastolic blood pressure). Increasing carotid cross sectional compliance reflects high carotid distensibility and low stiffness, and vice versa.
    Time FrameBaseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePediatric ControlAdult ControlMucopolysaccharidosis (MPS ) Subjects
    Arm/Group DescriptionHealthy pediatric control subjectsHealthy adult control subjectsMucopolysaccharidosis subjects type I, II, IIIA and VI.
    Measure Participants56055433
    Mean (Standard Deviation) [mm^2*mm Hg-1]
    0.16
    (0.05)
    0.11
    (0.04)
    0.14
    (0.08)
    4. Secondary Outcome
    TitleCarotid Incremental Elastic Modulus
    DescriptionA way of measuring the elasticity constant of the carotid vessel, has the unit mmHg and is defined by the equation 3(1+sD^2/dD^2)/cross sectional compliance value. In contrast to carotid cross sectional compliance and carotid cross sectional distensibility, increasing carotid incremental elastic modus reflects low carotid distensibility and high thickness.
    Time FrameBaseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePediatric ControlAdult ControlMucopolysaccharidosis (MPS ) Subjects
    Arm/Group DescriptionHealthy pediatric control subjectsHealthy adult control subjectsMucopolysaccharidosis subjects type I, II, IIIA and VI.
    Measure Participants56055433
    Median (Standard Deviation) [mm Hg]
    951
    (379.84)
    1859
    (755.3)
    1341
    (817.06)

    Adverse Events

    Time FrameThis is a chart review study that collected data at only one timepoint.
    Adverse Event Reporting Description There were no adverse events to be reported as this is a chart review study.
    Arm/Group TitleMPS PatientsPediatric ControlsAdult Controls
    Arm/Group DescriptionIndividuals with MPS disease (17 MPS I, 9 MPS II, 4 MPS IIIA , 3 MPS VI)Healthy pediatric control subjectsHealthy adult control subjects
    All Cause Mortality
    MPS PatientsPediatric ControlsAdult Controls
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/33 (0%) 0/560 (0%) 0/554 (0%)
    Serious Adverse Events
    MPS PatientsPediatric ControlsAdult Controls
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/33 (0%) 0/560 (0%) 0/554 (0%)
    Other (Not Including Serious) Adverse Events
    MPS PatientsPediatric ControlsAdult Controls
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/33 (0%) 0/560 (0%) 0/554 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleAaron Kelly PhD
    OrganizationUniversity of Minnesota
    Phone612-626-3492
    Emailkelly105@umn.edu
    Responsible Party:
    University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT01586871
    Other Study ID Numbers:
    • 1202M09721
    • U54NS065768
    First Posted:
    Apr 27, 2012
    Last Update Posted:
    Feb 24, 2021
    Last Verified:
    Feb 1, 2021