CADASIL Disease Discovery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02821780
Recruitment Status : Recruiting
First Posted : July 4, 2016
Last Update Posted : May 23, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief 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. Researchers want to study people who have CADASIL to learn more about it.


To learn more about CADASIL by studying people who have it.


People ages 18-100 who were diagnosed with CADASIL in the past 5 years and can make their own decisions


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.

Condition or disease
Cardiovascular Disease Arterial Stiffness

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 Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: CADASIL Disease Discovery
Study Start Date : June 29, 2016
Estimated Primary Completion Date : April 6, 2020
Estimated Study Completion Date : April 6, 2020

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Clinical evaluations will be used to determine whether disease progression can be assessed. [ Time Frame: 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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.


  • 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)
  • Subjects unable to remain supine for the expected length of the MRI (i.e. up to 1 hour)
  • Subjects with uncontrolled head movements
  • Subjects whose scans or examinations show brain abnormalities
  • Subjects who are claustrophobic for the expected length of the MRI (i.e. up to 1 hour)
  • Subjects who do not speak English

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02821780

Contact: Elisa A Ferrante, Ph.D. (301) 451-3457

United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Manfred Boehm, M.D. National Heart, Lung, and Blood Institute (NHLBI)

Additional Information:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI) Identifier: NCT02821780     History of Changes
Other Study ID Numbers: 160132
First Posted: July 4, 2016    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 10, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Biospecimen Procurement
Laboratory Research Specimens

Additional relevant MeSH terms:
Cerebral Arterial Diseases
Cardiovascular Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia, Vascular
Intracranial Arterial Diseases
Vascular Diseases
Genetic Diseases, Inborn