Trial Outcomes & Findings for Carotid Structure and Function in MPS Syndromes: A Multicenter Study of the Lysosomal Disease Network (NCT NCT01586871)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

1147 participants

Primary outcome timeframe

Baseline

Results posted on

2021-02-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Pediatric Control Patients The pediatric control patients were obtained from prior studies of insulin resistance and cardiovascular risk at the University of Minnesota.	Adult Controls The adult controls were obtained from prior studies of insulin resistance and cardiovascular risk at the University of Minnesota.	MPS Patients 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.
Overall Study STARTED	560	554	33
Overall Study COMPLETED	560	554	33
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pediatric Control n=560 Participants Healthy pediatric control subjects	Adult Control n=554 Participants Healthy adult control subjects	Mucopolysaccharidosis (MPS ) Subjects n=33 Participants Mucopolysaccharidosis subjects type I, II, IIIA and VI.	Total n=1147 Participants Total of all reporting groups
Age, Continuous	13.14 years STANDARD_DEVIATION 4.01 • n=5 Participants	39.16 years STANDARD_DEVIATION 2.24 • n=7 Participants	12.47 years STANDARD_DEVIATION 4.66 • n=5 Participants	21.59 years STANDARD_DEVIATION 3.63 • n=4 Participants
Sex: Female, Male Female	259 Participants n=5 Participants	285 Participants n=7 Participants	10 Participants n=5 Participants	554 Participants n=4 Participants
Sex: Female, Male Male	301 Participants n=5 Participants	269 Participants n=7 Participants	23 Participants n=5 Participants	593 Participants n=4 Participants
Height	155 centimeters STANDARD_DEVIATION 18.3 • n=5 Participants	171 centimeters STANDARD_DEVIATION 12.8 • n=7 Participants	132 centimeters STANDARD_DEVIATION 16.59 • n=5 Participants	152.66 centimeters STANDARD_DEVIATION 15.89 • n=4 Participants
Weight	53.8 kilograms STANDARD_DEVIATION 23.54 • n=5 Participants	86.39 kilograms STANDARD_DEVIATION 23.33 • n=7 Participants	36.66 kilograms STANDARD_DEVIATION 16.74 • n=5 Participants	58.95 kilograms STANDARD_DEVIATION 21.20 • n=4 Participants
Body Mass Index	21.44 Kg/m^2 STANDARD_DEVIATION 5.84 • n=5 Participants	29.46 Kg/m^2 STANDARD_DEVIATION 7.47 • n=7 Participants	20.03 Kg/m^2 STANDARD_DEVIATION 4.50 • n=5 Participants	23.64 Kg/m^2 STANDARD_DEVIATION 5.93 • n=4 Participants
Systolic blood pressure	106 mm Hg STANDARD_DEVIATION 10.42 • n=5 Participants	125 mm Hg STANDARD_DEVIATION 15.59 • n=7 Participants	106 mm Hg STANDARD_DEVIATION 10.98 • n=5 Participants	112.33 mm Hg STANDARD_DEVIATION 12.33 • n=4 Participants
Diastolic blood pressure	58 mm Hg STANDARD_DEVIATION 7.78 • n=5 Participants	71.97 mm Hg STANDARD_DEVIATION 10.39 • n=7 Participants	55 mm Hg STANDARD_DEVIATION 13.73 • n=5 Participants	61.65 mm Hg STANDARD_DEVIATION 10.63 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pediatric Control n=560 Participants Healthy pediatric control subjects	Adult Control n=554 Participants Healthy adult control subjects	Mucopolysaccharidosis (MPS ) Subjects n=33 Participants Mucopolysaccharidosis subjects type I, II, IIIA and VI.
Carotid Intima-media Thickness, Measured in Millimeters	0.44 mm Standard Deviation 0.04	0.52 mm Standard Deviation 0.09	0.56 mm Standard Deviation 0.05

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pediatric Control n=560 Participants Healthy pediatric control subjects	Adult Control n=554 Participants Healthy adult control subjects	Mucopolysaccharidosis (MPS ) Subjects n=33 Participants Mucopolysaccharidosis subjects type I, II, IIIA and VI.
Carotid Cross-sectional Distensibility	32.03 percentage of change Standard Deviation 8.35	16.33 percentage of change Standard Deviation 4.73	28.36 percentage of change Standard Deviation 15.70

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pediatric Control n=560 Participants Healthy pediatric control subjects	Adult Control n=554 Participants Healthy adult control subjects	Mucopolysaccharidosis (MPS ) Subjects n=33 Participants Mucopolysaccharidosis subjects type I, II, IIIA and VI.
Carotid Cross-sectional Compliance	0.16 mm^2*mm Hg-1 Standard Deviation 0.05	0.11 mm^2*mm Hg-1 Standard Deviation 0.04	0.14 mm^2*mm Hg-1 Standard Deviation 0.08

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pediatric Control n=560 Participants Healthy pediatric control subjects	Adult Control n=554 Participants Healthy adult control subjects	Mucopolysaccharidosis (MPS ) Subjects n=33 Participants Mucopolysaccharidosis subjects type I, II, IIIA and VI.
Carotid Incremental Elastic Modulus	951 mm Hg Standard Deviation 379.84	1859 mm Hg Standard Deviation 755.3	1341 mm Hg Standard Deviation 817.06

Adverse Events

MPS Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Pediatric Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Adult Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Aaron Kelly PhD

University of Minnesota

Phone: 612-626-3492

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place