Impact of Elastin Mediated Vascular Stiffness on End Organs

Brief Title

Impact of Elastin Mediated Vascular Stiffness on End Organs

Official Title

Impact of Elastin Mediated Vascular Stiffness on End Organs

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.
    

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. When telehealth
      is used, 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 Type

Observational


Primary Outcome

By testing both WS and SVAS subgroups, we can investigate both the effect of elastin insufficiency mediated vascular disease on end organs such as the heart, gut, kidneys and brain and look for a synergistic effect of the larger WS gene deletion...


Condition

Williams Syndrome


Study Arms / Comparison Groups

 Case
Description:  Subjects with WS/SVAS

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

200

Start Date

December 6, 2016

Completion Date

December 7, 2031

Primary Completion Date

December 7, 2031

Eligibility Criteria

        -  INCLUSION CRITERIA:

        We will recruit individuals with WS or SVAS 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).

          -  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 participating in the study as part of control group must:

          -  be between the ages of 5 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)
      

Gender

All

Ages

3 Years - 85 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Beth A Kozel, M.D., (301) 827-3237, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02840448

Organization ID

160144

Secondary IDs

16-H-0144

Responsible Party

Sponsor

Study Sponsor

National Heart, Lung, and Blood Institute (NHLBI)


Study Sponsor

Beth A Kozel, M.D., Principal Investigator, National Heart, Lung, and Blood Institute (NHLBI)


Verification Date

April 8, 2021