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

Mucopolysaccharidoses Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01586871
• Other study ID #: 1202M09721
• Secondary ID: U54NS065768
• Status: Completed
• Start date: March 2012
• Est. completion date: June 2017

Study information

• Verified date: February 2021
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1147
• Est. completion date: June 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Mucopolysaccharidoses

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota
United States	Children's Hospital of Orange County	Orange	California

Sponsors (5)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Carotid Intima-media Thickness, Measured in Millimeters	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.	Baseline
Secondary	Carotid Cross-sectional Distensibility	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.	Baseline
Secondary	Carotid Cross-sectional Compliance	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.	Baseline
Secondary	Carotid Incremental Elastic Modulus	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.	Baseline

External Links

•   Rare Disease Clinical Research Network