Germline Mutation in the NOTCH 3 GeneNCT02821780
CADASIL Disease Discovery
An observational study of Germline Mutation in the NOTCH 3 Gene and Cardiovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
Trial summary
Cerebral autosomal dominant arteriopathy with subcortical infarct (CADASIL) is a lethal disease caused by a gene mutation that affects arteries in the brain. Symptoms include migraines, strokes, memory loss, and dementia. There are no treatments. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Germline Mutation in the NOTCH 3 Gene, Cardiovascular Disease, Arterial Stiffness
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Oct 2016to 3 May 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Study population: Male or female, age 18 to 100 years (inclusive). Established diagnosis of CADASIL, as determined by genetic testing, in early stages of disease (0-5 years after diagnosis) with mild or no cognitive impairment
Who may be able to join
- Male or female, age 18 to 100 years (inclusive).
- Established diagnosis of CADASIL, as determined by genetic testing, in early stages of disease (0-5 years after diagnosis) with mild or no cognitive impairment.
- Willing and able to comply with study requirements.
Who cannot join
- Subjects unable to give informed consent without requirement for a legally authorized representative
- Subjects who decline to provide samples for blood and/or tissue studies, or who do not consent to have samples stored for future research
- Pregnant women are excluded due to study procedures (pregnancy test will be done in females of childbearing age under other NHLBI-approved protocols the subject is consented to, up to 48 hours prior to consenting to this protocol).
- Subjects unable to undergo an MRI scan
- 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)
Show all 11Show fewer
- 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.
- Subjects whose scans or examinations show unexpected brain conditions.
- Subjects who do not speak English
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Nationwide Children s Hospital
Columbus, Ohio, 43205
About this study
Cerebral autosomal dominant arteriopathy with subcortical infarct (CADASIL) is a lethal disease caused by a gene mutation that affects arteries in the brain. Symptoms include migraines, strokes, memory loss, and dementia. There are no treatments. Researchers want to study people who have CADASIL to learn more about it.
Objectives:
Read more
To learn more about CADASIL by studying people who have it.
Eligibility:
People ages 18-100 who were diagnosed with CADASIL in the past 5 years and can make their own decisions
Design:
Participants will be screened in another NIH protocol.
Participants will have 3 visits over 2 years. These may include:
- Physical exam
- Thinking and concentration tests
- Blood tests
- Skin biopsy: A small skin punch is removed from the arm or leg
- Eye exam and eye imaging tests
- Fluorescein angiogram: A catheter is placed in an arm vein. Dye is given through the catheter and travels to the eyes.
- EndoPAT: A small clamp on the fingertip measures blood volume.
- Cardio-ankle vascular index (CAVI): Artery stiffness is tested with blood pressure cuffs on the arms and legs. Soft electrodes on the skin measure heart signals.
- Brain MRI or MRA: They lie on a table that slides in and out of a tube that takes pictures. They may get a contrast agent in their vein. It brightens the brain so researchers can see where blood flows.
- CT scan of the heart: They lie on a table that slides in and out of a machine that takes pictures.
- They get contrast dye injected through a catheter. They may get a medicine that makes their blood vessels bigger or slows their heart rate.
Read the detailed description
Small vessel diseases are conditions characterized by the narrowing of small arteries leading to an imbalance of blood supply upon demand. This results in a progressive chronic hypoperfusion with detrimental outcomes for the affected organ system and for the patient. Recent advances in genetic evaluation have identified several genetic variants causing cerebrovascular small vessel diseases. These diseases have common clinical presentation including recurrent strokes, progressive white matter degeneration, and debilitating dementia. The link between these pathologies is defects in the tunica media of arteries, which is composed mainly of vascular smooth muscle cells (vSMCs).
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy) is caused by mutations in NOTCH3. The disease is of slow onset, with initial clinical manifestations in the third and fourth decade of life, but progressive and fatal. Predominant clinical features include migraine with aura (atypical or isolated), strokes, memory loss, and multiple psychiatric symptoms including dementia. Currently, CADASIL is considered the most common hereditary subcortical vascular dementia, however, treatments are palliative, and there is little prospect of future therapies to directly address causation and block progression. We propose to characterize the etiology and natural history of CADASIL subjects through comprehensive clinical and molecular characterizations. Subjects will be seen at the National Institutes of Health (NIH) once a year for a period of 2 years (total of 3 visits).
- Conditions
- Germline Mutation in the NOTCH 3 Gene, Cardiovascular Disease, Arterial Stiffness, Pathogenesis of CADASIL, Clinical Phenotype of CADASIL
- Keywords
- Stroke, progressive white matter degeneration, and debilitating dementia., progressive chronic hypoperfusion, Biospecimen Procurement, Laboratory Research Specimens, Natural History
- Medical subject headings
- Cardiovascular Diseases, Stroke
What is being measured
The primary outcome is the main question the study is designed to answer.
To study the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected and unaffected cohorts (as reference biospecimens).
pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens
Measured: 2 years
Secondary outcomes (1)
Clinical evaluations will be used to determine whether disease progression can be assessed.
Therefore, we will perform a comprehensive clinical and molecular assessment to determine possible correlations between clinical phenotypes, histological biopsy read-outs, and molecular findings
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2016 (estimated)
- Study start18 Oct 2016
- Primary completion3 May 2022
- Study completion3 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Germline Mutation in the NOTCH 3 GeneStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Manfred Boehm, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02821780
- Sponsor's protocol ID
- 160132
- Other IDs
- 16-H-0132
- Status last verified
- 10 Aug 2026
- First submitted
- 29 Jun 2016
- Last updated
- 27 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CADASIL Disease Discovery
- ClinicalTrials.gov ID
- NCT02821780
- Acronym / sponsor ID
- 160132
- Conditions
- Germline Mutation in the NOTCH 3 Gene, Cardiovascular Disease, Arterial Stiffness, Pathogenesis of CADASIL, Clinical Phenotype of CADASIL
- Keywords
- Stroke, progressive white matter degeneration, and debilitating dementia., progressive chronic hypoperfusion, Biospecimen Procurement, Laboratory Research Specimens, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 18 Oct 2016 (actual)
- Primary completion
- 3 May 2022 (actual)
- Study completion
- 3 May 2022 (actual)
- First posted
- 4 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cerebral autosomal dominant arteriopathy with subcortical infarct (CADASIL) is a lethal disease caused by a gene mutation that affects arteries in the brain. Symptoms include migraines, strokes, memory loss, and dementia. There are no treatments. Researchers want to study people who have CADASIL to learn more about it.
Objectives:
To learn more about CADASIL by studying people who have it.
Eligibility:
People ages 18-100 who were diagnosed with CADASIL in the past 5 years and can make their own decisions
Design:
Participants will be screened in another NIH protocol.
Participants will have 3 visits over 2 years. These may include:
- Physical exam
- Thinking and concentration tests
- Blood tests
- Skin biopsy: A small skin punch is removed from the arm or leg
- Eye exam and eye imaging tests
- Fluorescein angiogram: A catheter is placed in an arm vein. Dye is given through the catheter and travels to the eyes.
- EndoPAT: A small clamp on the fingertip measures blood volume.
- Cardio-ankle vascular index (CAVI): Artery stiffness is tested with blood pressure cuffs on the arms and legs. Soft electrodes on the skin measure heart signals.
- Brain MRI or MRA: They lie on a table that slides in and out of a tube that takes pictures. They may get a contrast agent in their vein. It brightens the brain so researchers can see where blood flows.
- CT scan of the heart: They lie on a table that slides in and out of a machine that takes pictures.
- They get contrast dye injected through a catheter. They may get a medicine that makes their blood vessels bigger or slows their heart rate.
Detailed description
Small vessel diseases are conditions characterized by the narrowing of small arteries leading to an imbalance of blood supply upon demand. This results in a progressive chronic hypoperfusion with detrimental outcomes for the affected organ system and for the patient. Recent advances in genetic evaluation have identified several genetic variants causing cerebrovascular small vessel diseases. These diseases have common clinical presentation including recurrent strokes, progressive white matter degeneration, and debilitating dementia. The link between these pathologies is defects in the tunica media of arteries, which is composed mainly of vascular smooth muscle cells (vSMCs).
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy) is caused by mutations in NOTCH3. The disease is of slow onset, with initial clinical manifestations in the third and fourth decade of life, but progressive and fatal. Predominant clinical features include migraine with aura (atypical or isolated), strokes, memory loss, and multiple psychiatric symptoms including dementia. Currently, CADASIL is considered the most common hereditary subcortical vascular dementia, however, treatments are palliative, and there is little prospect of future therapies to directly address causation and block progression. We propose to characterize the etiology and natural history of CADASIL subjects through comprehensive clinical and molecular characterizations. Subjects will be seen at the National Institutes of Health (NIH) once a year for a period of 2 years (total of 3 visits).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male or female, age 18 to 100 years (inclusive). Established diagnosis of CADASIL, as determined by genetic testing, in early stages of disease (0-5 years after diagnosis) with mild or no cognitive impairment
Key inclusion criteria (3 listed)
- Male or female, age 18 to 100 years (inclusive).
- Established diagnosis of CADASIL, as determined by genetic testing, in early stages of disease (0-5 years after diagnosis) with mild or no cognitive impairment.
- Willing and able to comply with study requirements.
Key exclusion criteria (11 listed)
- Subjects unable to give informed consent without requirement for a legally authorized representative
- Subjects who decline to provide samples for blood and/or tissue studies, or who do not consent to have samples stored for future research
- Pregnant women are excluded due to study procedures (pregnancy test will be done in females of childbearing age under other NHLBI-approved protocols the subject is consented to, up to 48 hours prior to consenting to this protocol).
- Subjects unable to undergo an MRI scan
- Subjects whose scans or examinations show unexpected brain conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To study the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected and unaffected cohorts (as reference biospecimens).
Time frame: 2 years
pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens
1 secondary outcome
Clinical evaluations will be used to determine whether disease progression can be assessed.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Germline Mutation in the NOTCH 3 Gene
RecruitingObservational study
Natural History Study of CADASIL
Cardiovascular Disease, Arterial Stiffness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manfred Boehm, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Germline Mutation in the NOTCH 3 Gene and Cardiovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To study the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected and unaffected cohorts (as reference biospecimens). (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.