Cardiovascular Structure and Function in the Mucopolysaccharidoses

Summary

This study's investigators previously demonstrated the potential utility of non-invasive carotid ultrasonography to calculate carotid intima media thickness (cIMT) and stiffness (as measured by the three parameters, carotid cross-sectional distensibility \[cCSD\], carotid cross-sectional compliance \[cCSC\], and carotid incremental elastic modulus \[cIEM\]) in people with mucopolysaccharidoses (MPS).

Investigators also studied arterial gene expression in animal models of MPS, and identified upregulation of a number of markers potentially tied to atherosclerosis and inflammation. These include the atherosclerotic marker known as Clusterin (CLU), Cathepsin S, Elastin, and the inflammatory cytokines interleukin 1-α, interleukin 1-β, interleukin 2, and interleukin 6. Other studies have identified elevation in circulating tumor necrosis factor-α correlating with pain and physical disability in certain mucopolysaccharidoses.

Since these studies are cross sectional, and not longitudinal, this study aims to annually measure these previously studied biomarkers (carotid measurements, circulating cytokines, cathepsin S, elastin, and CLU) in a large cohort of MPS patients. This study is a 3-year, prospective, anonymized, longitudinal assessment of cardiovascular structure, function, and circulating biomarkers in patients with mucopolysaccharidoses.

Conditions

• Mucopolysaccharidoses
• Carotid Disease
• Cardiac Disease
• Inflammation

Interventions

DIAGNOSTIC_TEST

Carotid ultrasonography

1. Study takes 10 - 15 minutes to complete 2. Subject will be asked to lay still and quietly during procedure 3. The ultrasound probe will be placed on one side of the neck to capture images of the carotid artery. When images from one side have been captured, the probe will be moved to the other side of the neck to capture images from the other carotid artery. 4. Blood pressure and heart rate will be obtained during the study 5. Results will be anonymized, digitized and stored on CD with unique identifier

DIAGNOSTIC_TEST

Echocardiography, transthoracic

1. Study takes 15 - 20 minutes to complete 2. Subject will be asked to lay still and quietly during procedure 3. The technician will apply an ultrasound probe to the chest. Images and movies will be acquired. 4. Results will be digitized and stored on CD

PROCEDURE

Venipuncture

1. 10 mL of blood total will be drawn (5 mL in a blue top citrate tube, 5 mL in a purple top EDTA tube). Measurements of cytokines, clusterin, lipidomics, cathepsin S protease, and elastin (previously identified potential biomarker candidates) will be performed. 2. Blood will preferably be drawn via venipuncture, but if patient has a port-a-cath already implanted and is having blood drawn via port-a-cath for clinically required reasons, then study-related blood draw via port-a-cath can take place concurrently with clinically required blood draws.

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc

  collaborator INDUSTRY

• Children's Hospital of Orange County

  lead OTHER

Principal Investigators

• Raymond Wang, M.D. · CHOC Children's Hospital

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-13

Primary Completion

2026-06-30

Completion

2026-06-30

Countries

• United States

Study Locations