Natural History Study of CADASIL

NCT05072483 | Recruiting

• 2 other identifiers: 10000413000413-H
• Study Type: observational
• Target: 155
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• This study will examine the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected individuals.

  To study the pathogenesis of CADASIL and obtain clinical evaluations and biospecimens from affected cohorts to identify underlying disease mechanism(s).

  13 years

Secondary Outcomes (1)

• Clinical evaluations will be used to investigate variability of clinical phenotype during the study period.

  20 years

Study Arms (2)

Healthy controls

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

Device: MRI

Subjects with CADASIL

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

Device: MRI

Interventions

MRI DEVICE

Research pulse sequences.

Healthy controls; Subjects with CADASIL

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

We will follow up to 110 subjects in order to have 100 subjects with CADASIL (at least 80 new CADASIL subjects and up to 20 CADASIL subjects previously enrolled in our pilot study, if they would like to participate in this study as well) and up to 45 healthy controls with the goal of 40 healthy control subjects completing the study, withtotal accrual of 155 male and female, ages 18-100. Should anyone from the original patient cohort decide not to participate in this new study, additional patients will be recruited in order to meet our goal of having 100 CADASIL subjects enrolled in the study.

You may qualify if:

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

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy at time of consent.
• Subjects who lack capacity to consent and don't have a legally authorized representative.
• Subjects who decline to provide samples for blood and/or tissue studies.
• Subjects who do not speak English.
• Subjects whose scans or examinations show unexpected brain conditions (outside of CADASIL) which would interfere with interpretation of testing.
• 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 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cardiovascular Diseases; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Study Officials

• Elisa A Ferrante Brenlla, Ph.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

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

Elisa A Ferrante Brenlla, Ph.D.

CONTACT

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

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: October 11, 2021
• Study Start: April 18, 2022
• Primary Completion (Estimated): June 1, 2034
• Study Completion (Estimated): June 1, 2041
• Last Updated: February 25, 2026

Record last verified: 2026-02-18

Locations

US (1)