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Active, Not Recruiting

NCT Number: NCT05063435

Cardiovascular Structure and Function in the Mucopolysaccharidoses

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Mucopolysaccharidoses Carbohydrate Metabolism, Inborn Errors Cardiac Disease Cardiovascular Diseases Carotid Disease Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Heart Diseases Inflammation Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Skin and Connective Tissue Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

Children's Hospital of Orange County

Orange, California, 92868, United States

About this study

Specific Aims

  • Annually assess cardiac and carotid structure and function utilizing ultrasonography, in patients with mucopolysaccharidoses
  • Annually measure circulating levels of clusterin, elastin, cathepsin S, lipids, and cytokines in patients with mucopolysaccharidoses

Target enrollment 30 subjects at CHOC Children's Hospital

Study Protocol

Screening

  • Study Investigators will identify eligible patients to participate in the study from their current patient population and future referrals.
  • Eligible patients will be provided with study information on the study during their standard of care metabolic clinic visit.

Informed Consent

  • Informed consent will be obtained following the requirements set forth by 21 CFR 50.25.
  • Patients interested in the study will be provided the informed consent document. The document will be reviewed in a private quiet room and ample time for questions will be provided. The patient can keep a copy of the consent if they wish to discuss the study with friends and family. Consent will only be obtained once the patient has had time to ask questions and is aware that the study is completely voluntary.

Initial entry

  • Information regarding age, sex, MPS diagnosis (including genetic mutation and enzymatic levels, if possible) will be obtained
  • Height and weight will be obtained. If patient has had a recent (within 3 months) evaluation at CHOC Children's with height and weight, those parameters may be used
  • Medical records will be obtained specifically focusing upon
  • the genetic and/or enzymatic testing used to confirm the MPS diagnosis
  • the treatment status (treated or not) and duration of treatment (calculated by the difference between date of first carotid imaging and date of first treatment)
  • Carotid ultrasonography will be obtained
  • Study takes 10 - 15 minutes to complete
  • Subject will be asked to lay still and quietly during procedure
  • Blood pressure and heart rate will be obtained during the study
  • Results will be digitized and stored on CD
  • Echocardiography will be obtained
  • Study takes 15 - 20 minutes to complete
  • Subject will be asked to lay still and quietly during procedure
  • Results will be digitized and stored on CD
  • Venipuncture / phlebotomy
  • 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.
  • 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.

Annual studies Procedures 2), 4), 5), and 6) will be repeated on an annual basis for a total of three years

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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

Treatment and study plan

Carotid ultrasonography

Diagnostic Test
  • Study takes 10 - 15 minutes to complete
  • Subject will be asked to lay still and quietly during procedure
  • 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.
  • Blood pressure and heart rate will be obtained during the study
  • Results will be anonymized, digitized and stored on CD with unique identifier

Other names: Carotid ultrasound

Echocardiography, transthoracic

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

Other names: Echocardiogram

Venipuncture

Procedure
  • 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.
  • 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.

Other names: Blood draw, Phlebotomy

Primary outcomes

  1. Cardiovascular Event

    Time frame: 3 years

    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

Secondary outcomes

  1. Age

    Time frame: 3 years

    Change of age of subject (unit: years)

  2. Height

    Time frame: 3 years

    Change of height of subject (unit: meters)

  3. Weight

    Time frame: 3 years

    Change of weight of subject (unit: kilograms)

  4. Blood pressure

    Time frame: 3 years

    Change in systolic and diastolic blood pressure over the duration of the study (unit: millimeters of mercury)

  5. Carotid structure

    Time frame: 3 years

    Change in carotid intima media thickness over the duration of the study (mm).

  6. Carotid stiffness

    Time frame: 3 years

    Change in carotid cross-sectional distensibility over the duration of the study (unit: %). This metric is acquired in the carotid ultrasound, and measures the stiffness of the carotid artery via quantitation of the difference between end-systolic and end-diastolic carotid diameter.

  7. Cardiac structure (left ventricle)

    Time frame: 3 years

    Change in left ventricular mass index over the duration of the study (unit: grams / m2 body surface area). This metric is acquired in the echocardiogram, and quantitates the amount of myocardium in the left ventricle.

  8. Cardiac structure (aortic root diameter)

    Time frame: 3 years

    Change in aortic root measurement over the duration of the study (unit: mm). This metric is acquired in the echocardiogram, and quantitates the width of the aortic root.

  9. Mitral valve function

    Time frame: 3 years

    Assessment of changes in mitral valve function over the duration of the study (unit: 4 point Likert scale from 0 [none] to 4 [severe]). This metric is acquired during the echocardiogram, and assess the degree of mitral valve insufficiency.

  10. Aortic valve function

    Time frame: 3 years

    Assessment of changes in aortic valve function over the duration of the study (unit: 4 point Likert scale from 0 [none] to 4 [severe]). This metric is acquired during the echocardiogram, and assess the degree of aortic valve insufficiency.

  11. Inflammatory biomarkers (Tumor Necrosis Factor - alpha)

    Time frame: 3 years

    Change in plasma TNFa over the duration of the study.

  12. Inflammatory biomarkers (Cathepsin S)

    Time frame: 3 years

    Change in plasma Cathepsin S over the duration of the study. (Unit: mcg/L)

  13. Inflammatory biomarkers (Elastin)

    Time frame: 3 years

    Change in plasma Elastin levels over the duration of the study. (Unit: ng/mL)

  14. Inflammatory biomarkers (Clusterin)

    Time frame: 3 years

    Change in plasma clusterin levels over the duration of the study. (Unit: mcg/mL)

  15. Inflammatory biomarkers (lipidomics)

    Time frame: 3 years

    Change in plasma lipid levels over the duration of the study. (Unit: mcmol/L)

Sponsors and collaborators

Lead sponsor

Children's Hospital of Orange County

Other

Collaborators

  • Ultragenyx Pharmaceutical Inc

Registry information

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Oct 1, 2021
Registry last updated
Jan 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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