Recruiting

Observational Study

Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Code:

NCT05072483

Conditions

Cardiovascular Disease

Arterial Stiffness

Germline Mutation in the NOTCH 3 Gene

Pathogenesis of CADASIL

Clinical Phenotype of CADASIL

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

MRI

Study Details

Brief summary:

Background:

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy) is a genetic disorder. It causes narrowing of the small blood vessels and can lead to strokes and dementia. Researchers want to monitor people with CADASIL over time.

Objective:

To learn more about how CADASIL affects a person s blood vessels over time.

Eligibility:

Adults ages 18 and older who have CADASIL, and healthy volunteers.

Design:

Participants will be screened with a medical record review.

Participants will have 4 study visits over 9 years. Visits will last 6 8 hours per day, for 2 4 days.

Participants will give blood and urine samples. They will have an electrocardiogram to record their heart s electrical activity. They will fill out a family tree. They will have tests that measure mental abilities like memory and attention. They may have a skin biopsy. They may have a lumbar puncture.

Participants will have an eye exam. Their pupils will be dilated. They will receive a dye via intravenous (IV) line. Pictures will be taken of their eyes.

Participants will have an imaging scan of their brain. They may receive a contrast agent via IV.

Participants blood flow and blood vessel flexibility will be measured. In one test, a probe will be pressed against the skin of the their wrist, neck, and groin. In another test, they will hold one arm still while a microscope makes videos of the blood flow through a fingernail. In another test, they will perform light exercise or other activities while wearing an elastic band around their head or probes placed on their arm or leg.

Healthy volunteers will complete some of the above tests.

Conditions

Cardiovascular Disease

Arterial Stiffness

Germline Mutation in the NOTCH 3 Gene

Pathogenesis of CADASIL

Clinical Phenotype of CADASIL

Study ID

NCT05072483

Start date

Apr 18, 2022

Status verified date

Aug 19, 2026

Completion date

Jun 1, 2041

Anticipated

Primary completion date

Jun 1, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

  • INCLUSION CRITERIA:

Eligibility for this study may be determined based on information collected under other NHLBI-approved protocols, outside records and patient report.

In order to be eligible to participate in this study, an individual must meet criteria 1 \& 2 and either criteria 3 or 4:

1. Stated willingness to comply with all study procedures and availability for the duration of the study.
2. Male or female, aged 18 to 100 years (inclusive).
3. Established diagnosis of CADASIL or NOTCH3 mutations, as determined by genetic testing.
4. Healthy controls.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pregnancy at time of consent.
2. Subjects who lack capacity to consent and don't have a legally authorized representative.
3. Subjects who decline to provide samples for blood and/or tissue studies.
4. Subjects who do not speak English.
5. Subjects whose scans or examinations show unexpected brain conditions (outside of CADASIL) which would interfere with interpretation of testing.
6. Subjects unable to undergo an MRI scan or subjects meeting the following criteria:

  • Subjects who have internal non-MRI compatible metals (i.e., cardiac pacemaker, brain stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear implants, artificial heart valves or metal fragments in the eye) as these rendering an MRI unsafe
  • Subjects with ferromagnetic dental bridges or crowns (exclusion only for 7.0T)
  • Subjects unable to remain supine for the expected length of the MRI (i.e., up to 1 hour)
  • Subjects with uncontrolled head movements
  • Subjects who are claustrophobic for the expected length of the MRI (i.e., up to 1 hour) and claustrophobia cannot be controlled with anti-anxiety medication.

Study Design

Enrollment

155 participants

Anticipated

Interventions and Outcome Measures

Arms

Healthy controls

Healthy controls for exploratory analyses, where the measurements were not commonly performed previously in other populations, for qualitative comparison with CADASIL population

Subjects with CADASIL

Adult genetically-confirmed patients with a wider range of CADASIL disease duration and debility

Interventions

MRI

Research pulse sequences.

Primary outcome measure

  • This study will examine the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected individuals. [ Time Frame: 13 years ]

Central Contacts and Locations

Central contacts

William R Whalen, C.R.N.P.

(301) 402-9841william.whalen@nih.gov

Elisa A Ferrante Brenlla, Ph.D.

(301) 402-3577elisa.ferrante@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

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

800-411-1222prpl@cc.nih.gov

More Information

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Last update posted

Aug 21, 2026

Last verified

Aug 19, 2026

Keywords

  • Biospecimen Procurement
  • Laboratory Research Specimens
  • progressive chronic hypoperfusion
  • Stroke
  • progressive white matter degeneration, and debilitating dementia.

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Heart, Lung, and Blood Institute (NHLBI) on 2026-08-21.