Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Study

NCT ID: NCT05677880

Last Updated: 2026-01-15

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

660 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-03

Study Completion Date

2027-08-31

Brief Summary

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This is an observational study to better understand the risk factors and progression of CADASIL, a leading cause of vascular cognitive impairment and dementia (VCID). 575 participants will be enrolled and can expect to be on study for up to 5 years.

Detailed Description

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Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common monogenic vascular dementia. Individuals with CADASIL are destined to develop vascular cognitive impairment and dementia (VCID), which can be studied in pre-symptomatic and prodromal disease stages to detect the earliest changes in biological fluids, neuroimaging, and the emerging phenotype of symptomatic VCID.

The objective of the proposed research is to exploit an autosomal dominant vascular dementia as a model to investigate specific features of VCID and to examine interactions with risk factors impacting the aging life course.

The study will enroll a total of 575 participants with a CADASIL family history who have had a genetic test for a NOTCH3 variant. Participants will complete: a clinical interview, a neurological exam, neurocognitive and behavior assessments, MRI, and a blood draw at each study visit. Participants will complete 3 in-person visits in total as part of this study: baseline, visit 2 (18 months after baseline), visit 3 (36 months after baseline). Additional contact will occur by phone, mail, email or the internet as needed and will be referred to as "remote visits".

Conditions

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CADASIL

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Non-Carrier Cohort

About 100 participants who are at-risk, healthy family members with No NOTCH3 Mutation and no symptoms or signs of cognitive decline.

Study Procedures

Intervention Type OTHER

Participants will experience

* Neurocognitive Tests and Self-Report Measures
* Clinical Interviews
* Neurological Exam
* MRI screening at baseline, 18 months, 36 months
* Fasted Blood draw

Pre-Symptomatic NOTCH3 Cohort

About 133 participants who are pre-symptomatic, at-risk, and healthy (with verified NOTCH3 mutation) family members with no symptoms.

Study Procedures

Intervention Type OTHER

Participants will experience

* Neurocognitive Tests and Self-Report Measures
* Clinical Interviews
* Neurological Exam
* MRI screening at baseline, 18 months, 36 months
* Fasted Blood draw

Symptomatic NOTCH3 Cohort - No Functional Decline

About 134 participants who are symptomatic (with verified NOTCH3 mutation) family members and no functional decline (e.g., mild cognitive impairment (MCI) with premorbid functional levels maintained).

Study Procedures

Intervention Type OTHER

Participants will experience

* Neurocognitive Tests and Self-Report Measures
* Clinical Interviews
* Neurological Exam
* MRI screening at baseline, 18 months, 36 months
* Fasted Blood draw

Symptomatic NOTCH3 Cohort - Functional Decline

About 133 participants who are symptomatic family members with a verified NOTCH3 CADASIL mutation and evidence of functional decline consistent with early dementia.

Study Procedures

Intervention Type OTHER

Participants will experience

* Neurocognitive Tests and Self-Report Measures
* Clinical Interviews
* Neurological Exam
* MRI screening at baseline, 18 months, 36 months
* Fasted Blood draw

Interventions

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Study Procedures

Participants will experience

* Neurocognitive Tests and Self-Report Measures
* Clinical Interviews
* Neurological Exam
* MRI screening at baseline, 18 months, 36 months
* Fasted Blood draw

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Must be at least 18 years old
2. Positive NOTCH3 genetic testing; OR a positive skin biopsy; OR a willingness to have a NOTCH3 genetic test completed prior to enrolling AND are at-risk for, or diagnosed clinically with, CADASIL
3. Willing to commit to three in-person visits (a baseline visit, an 18-month follow-up, and a 36-month follow-up) and to remote visits as needed by phone, email, mail or internet
4. Willing to provide documentation of all current medications to study team

a. All medications will be allowed throughout the course of study. Documentation of medications will be used for analyses to assess potential impact of medications on study outcomes.
5. Willing and able to undergo an MRI scan and blood draw at each in-person visit
6. Must have a designated "study companion"

a. A "study companion" is someone who knows the participant well (has greater than or equal to 3 hours/month of contact with the CADASIL participant) and can provide additional information to the study team (either remotely or in-person).
7. A functional capacity less than 4 on the Modified Rankin Scale


1\. Must meet same criteria as CADASIL participants, EXCEPT have negative NOTCH3 genetic testing

Exclusion Criteria

1. History of severe learning disability, intellectual disability, or other neurological disease or event not attributable to CADASIL
2. History of serious alcohol or drug abuse within the past year
3. Unwilling to undergo NOTCH3 genetic testing if there is no test on file
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jane S Paulsen, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Michael D Geschwind, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California

Los Angeles, California, United States

Site Status RECRUITING

University of California

San Francisco, California, United States

Site Status RECRUITING

University of Colorado

Denver, Colorado, United States

Site Status RECRUITING

Georgia State University Research Foundation

Atlanta, Georgia, United States

Site Status RECRUITING

Loyola University

Chicago, Illinois, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

Site Status RECRUITING

Brown University

Providence, Rhode Island, United States

Site Status RECRUITING

University of Texas Health Science Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

University of Texas

San Antonio, Texas, United States

Site Status NOT_YET_RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Cadasil Consortium

Role: CONTACT

1-833-795-3016

Related Links

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Other Identifiers

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2021-6179

Identifier Type: OTHER

Identifier Source: secondary_id

1RF1AG074608-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Protocol Version 8.0

Identifier Type: OTHER

Identifier Source: secondary_id

Neurology-Gen

Identifier Type: OTHER

Identifier Source: secondary_id

2021-1033

Identifier Type: -

Identifier Source: org_study_id

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