Mucopolysaccharidoses
Conditions
Keywords
MPS I, MPS II, MPS IIIA, MPS VI
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.
Interventions
None listed
Sponsors
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)
University of Minnesota
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
This 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.
Participants by arm
| Arm | Count |
|---|---|
| Pediatric Control Healthy pediatric control subjects | 560 |
| Adult Control Healthy adult control subjects | 554 |
| Mucopolysaccharidosis (MPS ) Subjects Mucopolysaccharidosis subjects type I, II, IIIA and VI. | 33 |
| Total | 1,147 |
Baseline characteristics
| Characteristic | Pediatric Control | Adult Control | Mucopolysaccharidosis (MPS ) Subjects | Total |
|---|---|---|---|---|
| Age, Continuous | 13.14 years STANDARD_DEVIATION 4.01 | 39.16 years STANDARD_DEVIATION 2.24 | 12.47 years STANDARD_DEVIATION 4.66 | 21.59 years STANDARD_DEVIATION 3.63 |
| Body Mass Index | 21.44 Kg/m^2 STANDARD_DEVIATION 5.84 | 29.46 Kg/m^2 STANDARD_DEVIATION 7.47 | 20.03 Kg/m^2 STANDARD_DEVIATION 4.5 | 23.64 Kg/m^2 STANDARD_DEVIATION 5.93 |
| Diastolic blood pressure | 58 mm Hg STANDARD_DEVIATION 7.78 | 71.97 mm Hg STANDARD_DEVIATION 10.39 | 55 mm Hg STANDARD_DEVIATION 13.73 | 61.65 mm Hg STANDARD_DEVIATION 10.63 |
| Height | 155 centimeters STANDARD_DEVIATION 18.3 | 171 centimeters STANDARD_DEVIATION 12.8 | 132 centimeters STANDARD_DEVIATION 16.59 | 152.66 centimeters STANDARD_DEVIATION 15.89 |
| Sex: Female, Male Female | 259 Participants | 285 Participants | 10 Participants | 554 Participants |
| Sex: Female, Male Male | 301 Participants | 269 Participants | 23 Participants | 593 Participants |
| Systolic blood pressure | 106 mm Hg STANDARD_DEVIATION 10.42 | 125 mm Hg STANDARD_DEVIATION 15.59 | 106 mm Hg STANDARD_DEVIATION 10.98 | 112.33 mm Hg STANDARD_DEVIATION 12.33 |
| Weight | 53.8 kilograms STANDARD_DEVIATION 23.54 | 86.39 kilograms STANDARD_DEVIATION 23.33 | 36.66 kilograms STANDARD_DEVIATION 16.74 | 58.95 kilograms STANDARD_DEVIATION 21.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 560 | 0 / 554 |
| other Total, other adverse events | 0 / 33 | 0 / 560 | 0 / 554 |
| serious Total, serious adverse events | 0 / 33 | 0 / 560 | 0 / 554 |
Outcome results
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Pediatric Control | Carotid Intima-media Thickness, Measured in Millimeters | 0.44 mm | Standard Deviation 0.04 |
| Adult Control | Carotid Intima-media Thickness, Measured in Millimeters | 0.52 mm | Standard Deviation 0.09 |
| Mucopolysaccharidosis (MPS ) Subjects | Carotid Intima-media Thickness, Measured in Millimeters | 0.56 mm | Standard Deviation 0.05 |
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Control | Carotid Cross-sectional Compliance | 0.16 mm^2*mm Hg-1 | Standard Deviation 0.05 |
| Adult Control | Carotid Cross-sectional Compliance | 0.11 mm^2*mm Hg-1 | Standard Deviation 0.04 |
| Mucopolysaccharidosis (MPS ) Subjects | Carotid Cross-sectional Compliance | 0.14 mm^2*mm Hg-1 | Standard Deviation 0.08 |
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Control | Carotid Cross-sectional Distensibility | 32.03 percentage of change | Standard Deviation 8.35 |
| Adult Control | Carotid Cross-sectional Distensibility | 16.33 percentage of change | Standard Deviation 4.73 |
| Mucopolysaccharidosis (MPS ) Subjects | Carotid Cross-sectional Distensibility | 28.36 percentage of change | Standard Deviation 15.7 |
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.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Pediatric Control | Carotid Incremental Elastic Modulus | 951 mm Hg | Standard Deviation 379.84 |
| Adult Control | Carotid Incremental Elastic Modulus | 1859 mm Hg | Standard Deviation 755.3 |
| Mucopolysaccharidosis (MPS ) Subjects | Carotid Incremental Elastic Modulus | 1341 mm Hg | Standard Deviation 817.06 |