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MucopolysaccharidosesNCT05063435

Cardiovascular Structure and Function in the Mucopolysaccharidoses

An observational study of Mucopolysaccharidoses and Carotid Disease, run by Children's Hospital of Orange County at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Any age
What is being tested?
Carotid ultrasonography, Echocardiography, transthoracic and Venipuncture
Type of treatment
Surgery or procedure
How many people
30 participants
Where
1 siteUnited States
Study dates
13 Oct 2021to 30 Jun 2026
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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).

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital of Orange County

    Orange, California, 92868

Other trials in United States

About this study

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.

Read the detailed description

Specific Aims

  1. Annually assess cardiac and carotid structure and function utilizing ultrasonography, in patients with mucopolysaccharidoses
  2. 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

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

Informed Consent

  1. Informed consent will be obtained following the requirements set forth by 21 CFR 50.25.
  2. 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

  1. Information regarding age, sex, MPS diagnosis (including genetic mutation and enzymatic levels, if possible) will be obtained
  2. 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
  3. Medical records will be obtained specifically focusing upon
  4. the genetic and/or enzymatic testing used to confirm the MPS diagnosis
  5. 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)
  6. Carotid ultrasonography will be obtained
  7. Study takes 10 - 15 minutes to complete
  8. Subject will be asked to lay still and quietly during procedure
  9. Blood pressure and heart rate will be obtained during the study
  10. Results will be digitized and stored on CD
  11. Echocardiography will be obtained
  12. Study takes 15 - 20 minutes to complete
  13. Subject will be asked to lay still and quietly during procedure
  14. Results will be digitized and stored on CD
  15. Venipuncture / phlebotomy
  16. 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.
  17. 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

Being tested
Carotid ultrasonography, Echocardiography, transthoracic, Venipuncture
Keywords
mucopolysaccharidosis, carotid, cardiac, cardiovascular, biomarker, longitudinal, observational
Medical subject headings
Mucopolysaccharidoses, Heart Diseases, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carotid ultrasonographyDiagnostic test

    Also called Carotid ultrasound

    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

  • Echocardiography, transthoracicDiagnostic test

    Also called Echocardiogram

    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

  • VenipunctureProcedure or surgery

    Also called Blood draw, Phlebotomy

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 3 years

Secondary outcomes (15)

  1. Age

    Change of age of subject (unit: years)

    Measured: 3 years

  2. Height

    Change of height of subject (unit: meters)

    Measured: 3 years

  3. Weight

    Change of weight of subject (unit: kilograms)

    Measured: 3 years

  4. Blood pressure

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

    Measured: 3 years

  5. Carotid structure

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

    Measured: 3 years

  6. Carotid stiffness

    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.

    Measured: 3 years

  7. Cardiac structure (left ventricle)

    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.

    Measured: 3 years

  8. Cardiac structure (aortic root diameter)

    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.

    Measured: 3 years

  9. Mitral valve function

    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.

    Measured: 3 years

  10. Aortic valve function

    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.

    Measured: 3 years

  11. Inflammatory biomarkers (Tumor Necrosis Factor - alpha)

    Change in plasma TNFa over the duration of the study.

    Measured: 3 years

  12. Inflammatory biomarkers (Cathepsin S)

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

    Measured: 3 years

  13. Inflammatory biomarkers (Elastin)

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

    Measured: 3 years

  14. Inflammatory biomarkers (Clusterin)

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

    Measured: 3 years

  15. Inflammatory biomarkers (lipidomics)

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

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2021
  2. Study start13 Oct 2021
  3. Primary completion30 Jun 2026 (estimated)
  4. Study completion30 Jun 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05063435
Sponsor's protocol ID
200107
Status last verified
Dec 2025
First submitted
15 Jul 2021
Last updated
7 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Since we are the sole site, we do not have any plans to share individual data at this point. Once the study has completed data collection and analysis, data will be shared in aggregate.

Publications

  • 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.

    PubMed 21963080

  • 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.

    PubMed 24268528

  • 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.

    PubMed 28294991

  • 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.

    PubMed 32183856

Questions about this trial

What is this clinical trial studying?

An observational study of Mucopolysaccharidoses and Carotid Disease, run by Children's Hospital of Orange County at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cardiovascular Event (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05063435, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.

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