Observing the progression of CADASIL over time

Natural History Study of CADASIL

This study is tracking people with CADASIL and healthy volunteers over nine years to see how the disease affects blood vessels and overall health.

Quick facts

• Study type: Observational
• Enrollment: 155 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05072483 on ClinicalTrials.gov

What this trial studies

This observational study aims to monitor individuals diagnosed with CADASIL, a genetic disorder affecting small blood vessels, to understand its impact on blood vessel health over time. Participants, including both CADASIL patients and healthy volunteers, will undergo a series of evaluations and tests over a nine-year period, including blood and urine sample collection, cognitive assessments, and imaging studies. The study will focus on the pathogenesis and clinical variability of CADASIL, utilizing biospecimens for molecular research. The goal is to gather comprehensive data to better understand the disease's progression and its effects on mental and physical health.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of CADASIL or NOTCH3 mutations, as well as healthy volunteers for comparison.

Not a fit: Patients who are pregnant, nursing, or unable to provide consent will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide valuable insights into the progression of CADASIL, potentially leading to improved management and treatment strategies for affected patients.

How similar studies have performed: While similar studies have explored CADASIL, this particular observational approach focusing on long-term progression and molecular evaluations is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

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:

1. Stated willingness to comply with all study procedures and availability for the duration of the study.
2. Male or female, aged 18 to 100 years (inclusive).
3. Established diagnosis of CADASIL or NOTCH3 mutations, as determined by genetic testing.
4. Healthy controls.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pregnancy at time of consent.
2. Subjects who lack capacity to consent and don't have a legally authorized representative.
3. Subjects who decline to provide samples for blood and/or tissue studies.
4. Subjects who do not speak English.
5. Subjects whose scans or examinations show unexpected brain conditions (outside of CADASIL) which would interfere with interpretation of testing.
6. 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.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Elisa A Ferrante Brenlla, Ph.D. — National Heart, Lung, and Blood Institute (NHLBI)
• Study coordinator: William R Whalen, C.R.N.P.

Conditions Cardiovascular Disease; Arterial Stiffness; Germline Mutation in the NOTCH 3 Gene; Pathogenesis of CADASIL; Clinical Phenotype of CADASIL; Biospecimen Procurement; Laboratory Research Specimens; progressive chronic hypoperfusion