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

Completed

• Conditions: Mucopolysaccharidoses

• Registration Number: NCT01586871
• Lead Sponsor: University of Minnesota

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-04-25
• Study First Submitted QC: 2012-04-25
• Study First Posted: 2012-04-27
• Primary Completion: 2016-08
• Study Completion: 2017-06
• Results First Submitted: 2020-11-12
• Results First Submitted QC: 2021-01-12
• Status Verified: 2021-02
• Results First Posted: 2021-02-03
• Last Update Submitted: 2021-02-05
• Last Update Posted: 2021-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1147

Inclusion Criteria

• Be between the ages of 3 and 18 years old
• Be diagnosed with MPS I, MPS II or MPS VI

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Exclusion Criteria

• None

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (2)

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States