Clinical Trial: CADASIL Disease Discovery

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: CADASIL Disease Discovery

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.

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 meas

Detailed Summary:

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).


Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Current 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 ]

Original Primary Outcome: Same as current

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

Original Secondary Outcome: Same as current

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: June 29, 2016
Date Started: June 16, 2016
Date Completion: April 6, 2020
Last Updated: April 21, 2017
Last Verified: December 7, 2016