Cardiovascular Structure and Function in the Mucopolysaccharidoses

NCT05063435 | Active Not Recruiting

• 1 other identifier: 200107
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

mucopolysaccharidosis; carotid; cardiac; cardiovascular; biomarker; longitudinal; observational

Outcome Measures

Primary Outcomes (1)

• Cardiovascular Event

  A cardiovascular event is defined by new onset of clinically significant aortic or mitral valve disease, aortic root dilatation, cardiomyopathy, reduction in cardiac contractile function, myocardial ischemia, myocardial infarction, or cerebrovascular accident

  3 years

Secondary Outcomes (15)

• Age

  3 years

• Height

  3 years

• Weight

  3 years

• Blood pressure

  3 years

• Carotid structure

  3 years

Interventions

Echocardiography, transthoracic DIAGNOSTIC_TEST

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

Also known as: Echocardiogram

Carotid ultrasonography DIAGNOSTIC_TEST

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

Also known as: Carotid ultrasound

Venipuncture PROCEDURE

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.

Also known as: Blood draw, Phlebotomy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any patient with a diagnosis of mucopolysaccharidosis who provides informed consent is eligible for this study. Mucopolysaccharidoses are a group of inherited metabolic disorders involving abnormal degradation of glycosaminoglycans. There are 11 different genes which, when altered, can give rise to a mucopolysaccharidosis. People with this diagnosis can develop significant cardiovascular disease (left ventricular hypertrophy, valvular dysfunction, aortic root dilatation, arterial wall thickening and stiffness).

You may qualify if:

• Any patient with a molecularly confirmed diagnosis of mucopolysaccharidosis is eligible to enroll in this study
• Parental / patient informed consent

You may not qualify if:

• Any reason that the investigators would deem a patient unable to participate in this study
• Inability to participate in the assessments required for this study

Sponsors & Collaborators

• Children's Hospital of Orange County: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Related Publications (4)

• Wang RY, Covault KK, Halcrow EM, Gardner AJ, Cao X, Newcomb RL, Dauben RD, Chang AC. Carotid intima-media thickness is increased in patients with mucopolysaccharidoses. Mol Genet Metab. 2011 Dec;104(4):592-6. doi: 10.1016/j.ymgme.2011.09.004. Epub 2011 Sep 10.

  PMID: 21963080 BACKGROUND

• Wang RY, Braunlin EA, Rudser KD, Dengel DR, Metzig AM, Covault KK, Polgreen LE, Shapiro E, Steinberger J, Kelly AS. Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness. Mol Genet Metab. 2014 Feb;111(2):128-32. doi: 10.1016/j.ymgme.2013.11.001. Epub 2013 Nov 12.

  PMID: 24268528 BACKGROUND

• Wang RY, Rudser KD, Dengel DR, Braunlin EA, Steinberger J, Jacobs DR, Sinaiko AR, Kelly AS. The Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls. Int J Mol Sci. 2017 Mar 15;18(3):637. doi: 10.3390/ijms18030637.

  PMID: 28294991 BACKGROUND

• Wang RY, Rudser KD, Dengel DR, Evanoff N, Steinberger J, Movsesyan N, Garrett R, Christensen K, Boylan D, Braddock SR, Shinawi M, Gan Q, Montano AM. Abnormally increased carotid intima media-thickness and elasticity in patients with Morquio A disease. Orphanet J Rare Dis. 2020 Mar 17;15(1):73. doi: 10.1186/s13023-020-1331-y.

  PMID: 32183856 BACKGROUND

MeSH Terms

Conditions

Mucopolysaccharidoses; Heart Diseases; Inflammation

Interventions

Ultrasonography, Carotid Arteries; Echocardiography; Phlebotomy; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ultrasonography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Cardiac Imaging Techniques; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Specimen Handling; Clinical Laboratory Techniques; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Raymond Wang, M.D.

  CHOC Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: October 1, 2021
• Study Start: October 13, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 7, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)