Natural History Study of CADASIL

NCT ID: NCT05072483

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

155 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-04-18

Study Completion Date

2041-06-01

Brief Summary

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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.

Detailed Description

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Study Description:

This is a disease discovery/natural history protocol. We will enroll up to 110 CADASIL subjects with the goal of 100 CADASIL subjects completing the study to perform in-depth prospective and retrospective evaluations for research purposes and up to 45 healthy control subjects with the goal of 40 completing the study for comparison.

Objectives:

Primary Objective: This study will examine the pathogenesis and progression of CADASIL through comprehensive evaluations, and molecular studies on biospecimens collected from affected individuals.

Secondary Objective: Comprehensive evaluations will be used to investigate variability of the genotype and clinical phenotype of CADASIL during the study period.

Exploratory Objective: Healthy controls may be used for comparison for some of the research testing where data on normal values is lacking. Healthy controls will not be used to establish normal range values but for qualitative comparison with CADASIL population.

Conditions

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Cardiovascular Disease Arterial Stiffness Germline Mutation in the NOTCH 3 Gene Pathogenesis of CADASIL Clinical Phenotype of CADASIL

Keywords

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

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Study Groups

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Healthy controls

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

MRI

Intervention Type DEVICE

Research pulse sequences.

Subjects with CADASIL

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

MRI

Intervention Type DEVICE

Research pulse sequences.

Interventions

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MRI

Research pulse sequences.

Intervention Type DEVICE

Eligibility Criteria

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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 or nursing 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elisa A Ferrante Brenlla, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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William R Whalen

Role: CONTACT

Phone: (301) 451-3315

Email: [email protected]

Elisa A Ferrante Brenlla, Ph.D.

Role: CONTACT

Phone: (301) 402-3577

Email: [email protected]

Facility Contacts

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

Role: primary

Related Links

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Other Identifiers

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000413-H

Identifier Type: -

Identifier Source: secondary_id

10000413

Identifier Type: -

Identifier Source: org_study_id