Impact of Elastin Mediated Vascular Stiffness on End Organs

NCT02840448 | Completed

• 2 other identifiers: 16014416-H-0144
• Study Type: observational
• Target: 159
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Williams Syndrome; Supravalvular Aortic Stenosis; Cardiovascular Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• By testing both WS and SVAS and WS gene region variation subgroups, we can investigate both the effect of elastin insufficiency mediated vascular disease on end organ function and look for a synergistic effect of the larger gene deletion on elas...

  Pilot studies aimed at identifying differences between the WS/SVAS/WS gene region variation population and controls.

  ongoing

Study Arms (2)

Case

Subjects with WS/SVAS/WS gene region variation

Controls

Healthy volunteers

Eligibility Criteria

• Age: 3 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary clinical along with matched healthy controls

You may qualify if:

• 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:

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Washington University School of medicine

St Louis, Missouri, 63110-1093, United States

Location

Related Publications (4)

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

  PMID: 20089974 BACKGROUND

• 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.

  PMID: 20409896 BACKGROUND

• 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.

  PMID: 21778438 BACKGROUND

• 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.

  PMID: 36752464 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Williams Syndrome; Aortic Stenosis, Supravalvular; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Ventricular Outflow Obstruction

Study Officials

• Manfred Boehm, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 21, 2016
• Study Start: December 2, 2016
• Primary Completion: April 6, 2024
• Study Completion: April 6, 2024
• Last Updated: April 27, 2026

Record last verified: 2026-04-23

Locations

US (2)