Impact of Elastin Mediated Vascular Stiffness on End Organs

NCT ID: NCT02840448

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

218 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-12-02

Study Completion Date

2032-02-25

Brief Summary

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Background:

People with Williams Syndrome (WS) and supravalvular aortic stenosis (SVAS) have less elasticity in their blood vessels. This is called blood vessel stiffness. Blood vessels may have focal narrowings called stenoses or may just be globally more narrow.

Objectives:

Researchers want to see how blood vessel differences in people with Williams Syndrome and supravalvular aortic stenosis affect organs in the body including the heart, gut, kidneys, and brain.

Eligibility:

People ages 3-85 who have WS or SVAS

Healthy volunteers ages 3-85

Design:

* Participants will have yearly visits for up to 10 years. All participants will be offered the same tests.
* Participants will give consent for the study team to review their medical records. If the participant is a child or an adult with WS, a parent or guardian will give the consent.
* Participants will visit the NIH where they will have a physical exam and medical history. Based on their health history, participants will undergo a series of imaging tests and measures of blood vessel function over the course of 2-4 days. Tests of cognitive abilites will also be performed. Blood will be drawn and an IV may be placed for specific tests.

Detailed Description

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Elasticity in the aorta buffers the body from damage due to pulsatile blood flow. Data from humans and mice show that with increasing age, vessels lose elasticity and become stiff. Vascular stiffness is associated with progressive cognitive impairment and dementia in aging adults, but little is known about the effects of early-onset/congenital vascular stiffness. Similarly, elastin-mediated arteriopathy in the form of stenosis has the potential to impact additional end organs such as the heart, lungs, gut, skeletal muscle and kidney causing feeding and exercise intolerance, as well hypertension. This study evaluates the impact of elastin arteriopathy and vascular stiffness on end organs.

Following consent, the investigators will work with the subjects and their caregivers to determine which tests are most appropriate for the patient based on their age/capabilities and preferences and may include:

* testing of cognitive and neurobehavioral abilities as well as measures of general health and well being
* undergo non-invasive measurements of vascular stiffness
* undergo brain imaging by MRI
* undergo echocardiogram
* undergo ECG
* undergo 24-hour ambulatory electrocardiogram monitor
* undergo ultrasound imaging and flow studies of various vascular beds and tissues
* undergo CT angiogram of relevant vessels
* undergo non-invasive tissue oxygenation and endothelial functional assessment with near infrared spectroscopy (NIRS) of the limbs and/or head/brain (fNIRS)
* perform a 6 minute walk test
* perform pulmonary function tests
* receive an eye exam and Optical coherence tomography (OCT)
* give blood/urine for relevant laboratories
* evaluate biomechanical properties of skin
* evaluate baseline fitness information using a fitness tracker
* complete medica photography evaluating relevant features of the condition
* receive a dental examination and dental photography

Visits may be conducted in person at the Clinical Center, by telehealth, or with a combination of in person and telehealth, at the discretion of the study team. All telehealth activities will be performed according to HRPP Policy 303 and only testing that can be performed at home (e.g. clinical consultations, neurobehavioral testing, fitness tracking, ambulatory ecg monitoring, and photography) will be selected. The other tests require the individual to be on site at the CC.

Consequently, some participants may have certain consultations at home and other testing on site to limit time in the CC

Additionally, the study will request permission to review the participant's medical records to obtain additional information about general and cardiovascular health. For individuals with supravalvular aortic stenosis (SVAS) or Williams syndrome (WS), the clinical report confirming the individuals diagnosis will be reviewed when available.

Conditions

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Williams Syndrome Supravalvular Aortic Stenosis Cardiovascular Disease

Keywords

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Williams Syndrome Blood Flow Brain Arterial Stiffness Natural History Variation in WS Genes

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Case

Subjects with WS/SVAS/WS gene region variation

No interventions assigned to this group

Controls

Healthy volunteers

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

We will recruit individuals with people with WS, SVAS or other WS region variation conditions (cases) and demographically similar control (unaffected) participants.

Children or adults with WS must:

* be between the ages of 3 and 85
* have a presumed or confirmed diagnosis of WS (genetic testing is not performed in this research study).
* have a parent/guardian available to provide consent and assist in answering medical questions
* not be pregnant

Children or adults with SVAS must:

* be between the ages of 3 and 85
* have clinical features suggestive of SVAS or an SVAS-like condition OR have no clinical features of SVAS or an SVAS-like condition but have genetic testing results that imply affected status (SVAS has decreased penetrance). No genetic testing will be done as part of this protocol.
* have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor (not applicable to adults)

Children or adults with WS region gene changes:

* be between the ages of 3 and 85
* have clinical or research genetic testing that reports gene variation in a non-ELN gene in the WS region.
* have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor or if they have cognitive impairment that would impede their ability to consent on their own behalf.

Children or adults participating in the study as part of control group must:

* be between the ages of 3 and 85
* not have clinical features or genetic profile suggestive of WS, SVAS or an SVAS-like condition. No genetic testing will be performed in this research study.
* have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor (not applicable to adults)
Minimum Eligible Age

3 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Manfred Boehm, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Washington University School of medicine

St Louis, Missouri, United States

Site Status COMPLETED

Countries

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United States

Central Contacts

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Elisa A Ferrante Brenlla, Ph.D.

Role: CONTACT

Phone: (301) 402-3577

Email: [email protected]

Manfred Boehm, M.D.

Role: CONTACT

Phone: (301) 435-7211

Email: [email protected]

Facility Contacts

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For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

References

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Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010 Jan 21;362(3):239-52. doi: 10.1056/NEJMra0903074. No abstract available.

Reference Type BACKGROUND
PMID: 20089974 (View on PubMed)

Franklin SS. Beyond blood pressure: Arterial stiffness as a new biomarker of cardiovascular disease. J Am Soc Hypertens. 2008 May-Jun;2(3):140-51. doi: 10.1016/j.jash.2007.09.002.

Reference Type BACKGROUND
PMID: 20409896 (View on PubMed)

Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Sep;42(9):2672-713. doi: 10.1161/STR.0b013e3182299496. Epub 2011 Jul 21.

Reference Type BACKGROUND
PMID: 21778438 (View on PubMed)

Levin MD, Cathey BM, Smith K, Osgood S, Raja N, Fu YP, Kozel BA. Heart Rate Variability Analysis May Identify Individuals With Williams-Beuren Syndrome at Risk of Sudden Death. JACC Clin Electrophysiol. 2023 Mar;9(3):359-370. doi: 10.1016/j.jacep.2022.10.010. Epub 2022 Nov 30.

Reference Type DERIVED
PMID: 36752464 (View on PubMed)

Related Links

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Other Identifiers

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16-H-0144

Identifier Type: -

Identifier Source: secondary_id

160144

Identifier Type: -

Identifier Source: org_study_id