Cardiovascular DiseaseNCT05072483
Natural History Study of CADASIL
An observational study of Cardiovascular Disease and Arterial Stiffness, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease, Arterial Stiffness, Germline Mutation in the NOTCH 3 Gene
- What is being tested?
- MRI
- Type of treatment
- Medical device
- How many people
- 155 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Apr 2022to 1 Jun 2041
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: We will follow up to 110 subjects in order to have 100 subjects with CADASIL (at least 80 new CADASIL subjects and up to 20 CADASIL subjects previously enrolled in our pilot study, if they would like to participate in this study as well) and up to 45 healthy controls with the goal of 40 healthy control subjects completing the study, withtotal accrual of 155 male and female, ages 18-100. Should anyone from the original patient cohort decide not to participate in this new study, additional patients will be recruited in order to meet our goal of having 100 CADASIL subjects enrolled in the study.
Who may be able to join
- 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:
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged 18 to 100 years (inclusive).
- Established diagnosis of CADASIL or NOTCH3 mutations, as determined by genetic testing.
- Healthy controls.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pregnancy at time of consent.
- Subjects who lack capacity to consent and don't have a legally authorized representative.
- Subjects who decline to provide samples for blood and/or tissue studies.
- Subjects who do not speak English.
- Subjects whose scans or examinations show unexpected brain conditions (outside of CADASIL) which would interfere with interpretation of testing.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Cardiovascular Disease, Arterial Stiffness, Germline Mutation in the NOTCH 3 Gene, Pathogenesis of CADASIL, Clinical Phenotype of CADASIL
- Being tested
- MRI
- Keywords
- Biospecimen Procurement, Laboratory Research Specimens, progressive chronic hypoperfusion, Stroke, progressive white matter degeneration, and debilitating dementia.
- Medical subject headings
- Cardiovascular Diseases, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDevice
Research pulse sequences.
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Healthy controls for exploratory analyses, where the measurements were not commonly performed previously in other populations, for qualitative comparison with CADASIL population Receives: Device: MRI | |
| Subjects with CADASIL | Adult genetically-confirmed patients with a wider range of CADASIL disease duration and debility Receives: Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
This study will examine the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected individuals.
To study the pathogenesis of CADASIL and obtain clinical evaluations and biospecimens from affected cohorts to identify underlying disease mechanism(s).
Measured: 13 years
Secondary outcomes (1)
Clinical evaluations will be used to investigate variability of clinical phenotype during the study period.
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.
Measured: 20 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2021
- Study start18 Apr 2022
- Primary completion1 Jun 2034 (estimated)
- Study completion1 Jun 2041 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elisa A Ferrante Brenlla, Ph.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05072483
- Sponsor's protocol ID
- 10000413
- Other IDs
- 000413-H
- Status last verified
- 6 Oct 2026
- First submitted
- 8 Oct 2021
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No