Recruiting

Observational Study

Sponsor:

University of Wisconsin, Madison

Code:

NCT05677880

Conditions

CADASIL

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Interventions

Study Procedures

Study Details

Brief summary:

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.

Conditions

CADASIL

Study ID

NCT05677880

Start date

Jun 3, 2022

Status verified date

Jan, 2026

Completion date

Aug, 2027

Anticipated

Primary completion date

Jun, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Inclusion Criteria for CADASIL Participants:

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

Inclusion Criteria for Healthy Controls (HC):

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

Study Design

Enrollment

660 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

Pre-Symptomatic NOTCH3 Cohort

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

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).

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.

Interventions

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

Primary outcome measure

  • Performance Measured by Change in Cognitive Executive Function Composite Z-Score [ Time Frame: baseline and 36 months ]
  • Change in total brain volume between baseline and 36 months [ Time Frame: baseline and 36 months ]
  • Change in total cerebral spinal volume between baseline and 36 months [ Time Frame: baseline and 36 months ]
  • Percent change in brain connectivity from baseline to 36 months [ Time Frame: baseline and 36 months ]
  • Change in Neurofilament Light (Nfl) [ Time Frame: baseline and 36 months ]
  • Change in World Health Organization Disability Assessment Schedule (WHODAS) Score [ Time Frame: baseline and 36 months ]
  • Change in CADASIL Severity Score [ Time Frame: baseline and 36 months ]

Central Contacts and Locations

Central contacts

Locations

University of California

Recruiting

Los Angeles, California, United States, 90095

University of California

Recruiting

San Francisco, California, United States, 94143

University of Colorado

Recruiting

Denver, Colorado, United States, 80204

Georgia State University Research Foundation

Recruiting

Atlanta, Georgia, United States, 30303

Loyola University

Recruiting

Chicago, Illinois, United States, 60660

Columbia University

Recruiting

New York, New York, United States, 10027

Oregon Health & Science University

Recruiting

Portland, Oregon, United States, 97239

Brown University

Recruiting

Providence, Rhode Island, United States, 02912

University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

University of Washington

Recruiting

Seattle, Washington, United States, 98195

More Information

Sponsor

University of Wisconsin, Madison

Last update posted

Jan 15, 2026

Last verified

Jan, 2026

Keywords

  • neurodegeneration
  • dementia
  • cognitive impairment
  • NOTCH3
  • vascular dementia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Wisconsin, Madison on 2026-01-15.