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

University of Wisconsin (UW)

Status: Enrolling

Conditions: CADASIL

Treatments: Other: Study Procedures

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05677880

1RF1AG074608-01 (U.S. NIH Grant/Contract)

Neurology-Gen (Other Identifier)

2021-6179 (Other Identifier)

Protocol Version 8.0 (Other Identifier)

2021-1033

Details and patient eligibility

About

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.

Full description

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".

Enrollment: 575 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

575 participants in 4 patient groups

Non-Carrier Cohort

Description:

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

Treatment:

Other: Study Procedures

Pre-Symptomatic NOTCH3 Cohort

Description:

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

Treatment:

Other: Study Procedures

Symptomatic NOTCH3 Cohort - No Functional Decline

Description:

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).

Treatment:

Other: Study Procedures

Symptomatic NOTCH3 Cohort - Functional Decline

Description:

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

Treatment:

Other: Study Procedures