Williams SyndromeNCT02840448
Impact of Elastin Mediated Vascular Stiffness on End Organs
An observational study of Williams Syndrome and Supravalvular Aortic Stenosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Williams Syndrome, Supravalvular Aortic Stenosis, Cardiovascular Disease
- How many people
- 159 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Dec 2016to 6 Apr 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 3 to 85 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Primary clinical along with matched healthy controls
Who may be able to join
- 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
Show all 18Show fewer
- 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)
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Washington University School of medicine
St Louis, Missouri, 63110-1093
About this study
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.
Read more
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.
Read the detailed description
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.
- Keywords
- Williams Syndrome, Blood Flow, Brain, Arterial Stiffness, Natural History, Variation in WS Genes
- Medical subject headings
- Williams Syndrome, Aortic Stenosis, Supravalvular, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case | Subjects with WS/SVAS/WS gene region variation | |
| Controls | Healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2016 (estimated)
- Study start2 Dec 2016
- Primary completion6 Apr 2024
- Study completion6 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Williams SyndromeStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Manfred Boehm, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02840448
- Sponsor's protocol ID
- 160144
- Other IDs
- 16-H-0144
- Status last verified
- 23 Apr 2026
- First submitted
- 19 Jul 2016
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010 Jan 21;362(3):239-52. doi: 10.1056/NEJMra0903074. No abstract available.
PubMed 20089974Franklin 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.
PubMed 20409896Gorelick 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.
PubMed 21778438Levin 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.
PubMed 36752464
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Elastin Mediated Vascular Stiffness on End Organs
- ClinicalTrials.gov ID
- NCT02840448
- Acronym / sponsor ID
- 160144
- Keywords
- Williams Syndrome, Blood Flow, Brain, Arterial Stiffness, Natural History, Variation in WS Genes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 2 Dec 2016 (actual)
- Primary completion
- 6 Apr 2024 (actual)
- Study completion
- 6 Apr 2024 (actual)
- First posted
- 21 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case | – | –Subjects with WS/SVAS/WS gene region variation |
| Controls | – | –Healthy volunteers |
Who may qualify
- Ages
- 3 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Primary clinical along with matched healthy controls
Key inclusion criteria (18 listed)
- We will recruit individuals with people with WS, SVAS or other WS region variation conditions (cases) and demographically similar control (unaffected) participants.
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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...
Time frame: ongoing
Pilot studies aimed at identifying differences between the WS/SVAS/WS gene region variation population and controls.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Background: PubMed 20089974Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010 Jan 21;362(3):239-52. doi: 10.1056/NEJMra0903074. No abstract available.
- Background: PubMed 20409896Franklin 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.
- Background: PubMed 21778438Gorelick 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.
- Derived from this study: PubMed 36752464Levin 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manfred Boehm, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Williams Syndrome and Supravalvular Aortic Stenosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites 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 18 inclusion and 0 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: finished, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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... (time frame: ongoing). 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 NCT02840448, 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 8 Oct 2026.