Natural History Study of CADASIL

Recruiting

• Conditions: Arterial Stiffness; Germline Mutation in the NOTCH 3 Gene; Cardiovascular Disease; Pathogenesis of CADASIL; Clinical Phenotype of CADASIL
• Interventions: Device: MRI

• Registration Number: NCT05072483
• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2021-10-08
• Study First Submitted QC: 2021-10-08
• Study First Posted: 2021-10-11
• Study Start: 2022-04-18
• Status Verified: 2025-04-16
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-18
• Primary Completion: 2034-06-01
• Study Completion: 2041-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subjects with CADASIL	MRI	Adult genetically-confirmed patients with a wider range of CADASIL disease duration and debility

Primary Outcome Measures

Name	Time	Method
This study will examine the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected individuals.	13 years	To study the pathogenesis of CADASIL and obtain clinical evaluations and biospecimens from affected cohorts to identify underlying disease mechanism(s).

Secondary Outcome Measures

Name	Time	Method
Clinical evaluations will be used to investigate variability of clinical phenotype during the study period.	20 years	To use Clinical evaluations to investigate variability of clinical phenotype during the study period. These studies will serve as baseline evaluations for future studies on the identification of underlying disease mechanism(s) and potential therapeutic approaches.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States