Clinical Research Directory

Long-term Prospective Study of Korean CADASIL Patients

K-CADASIL is a 10-year prospective study of 500 Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic brain disease that causes stroke and dementia. The investigators will track symptoms, brain scans, memory tests, and gene information to understand disease progression in Koreans and identify better treatments. Participants will visit clinics regularly for check-ups and blood tests. This study aims to help improve care for CADASIL patients and families worldwide.

Florida Cerebrovascular Disease Biorepository and Genomics Center

The purpose of this study is to create a state-wide biorepository and resource center for cerebrovascular diseases in Florida, which will include collecting medical history information and blood from subjects affected by cerebrovascular disease. The information and blood samples collected may be used in future research for the study of cerebrovascular disease and to learn about, prevent or treat other health problems.

RAre, But Not aLone: a Large Italian Network to Empower the Impervious diaGNostic Pathway of Rare cerEbrovascular Diseases (ALIGNED)

Cerebrovascular diseases (CVDs) are one leading cause of morbidity and mortality worldwide. Despite intensive investigations, more than 30% of strokes remain of undetermined origin. Rare Cerebrovascular Diseases (rCVDs), including heritable (i.e., CADASIL, COL4A1 syndrome, Fabry disease) and acquired conditions (i.e., Sneddon syndrome, Moyamoya arteriopathy) account for a proportion of these strokes. However, rCVDs are often misdiagnosed since clinicians are not able to recognize them. Although rare, the identification of these stroke causes is important to establish appropriate management measures, including genetic counselling, and, if available, therapy. The lack of data on phenotype and clinical course of rCVDs, given the paucity of published series, makes the diagnosis and the development of therapies challenging. Furthermore, the molecular characterization of rCVDs is still lacking, despite progresses achieved in common stroke by applying high throughput approaches as multi-omics. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, clinical and research activities are usually reserved to few specialized centers, mostly located in the North of Italy, leading patients to expensive trips for consultations. Therefore, the creation of a clinical and research network aimed at improving the diagnostic pathways of rCVDs is highly needed to improve the number of patients with rCVDs to better define the clinical phenotype and to transfer the knowledge on rCVDs in other centers overall Italy filling the geographical gap affecting Southern Italy.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Study

This is an observational study to better understand the risk factors and progression of CADASIL, a leading cause of vascular cognitive impairment and dementia (VCID). 575 participants will be enrolled and can expect to be on study for up to 5 years.

Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL

The project aims to retrospectively and prospectively analyze a population of CADASIL patients in order to study the natural history of the disease by correlating the symptom spectrum with genetic risk and specific neuroradiological and biological markers \- Stratifying patients according to their disease risk, this could contribute to the discovery of personalized therapeutic targets.

Development and Validation of a Functional MRI Biomarker of Cerebral Small Vessel Dysfunction in CADASIL

Cerebral small vessel diseases (cSVD) are diseases of brain tissue involving vessels (arterioles or capillaries) with a diameter of less than 400 microns. Within this group, CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is the most common familial form. CADASIL is due to mutations in the NOTCH3 gene located on chromosome 19. It is considered a unique model for the study of cSVD. CADASIL begins between the ages of 20 and 40, with the appearance of cerebral white matter hyper-signals visible on MRI. Before the age of 30, patients are usually asymptomatic. To date, there are no available treatments. To test new therapeutic approaches, we need biomarkers that are robust and sensitive enough to assess the effects of these treatments at an early stage of cSVD and over a relatively short period of time. An ideal monitoring biomarker should be repeatedly and safely usable, easily accessible, accurate, reproducible and sensitive to disease progression or pharmacological intervention. Alterations in neurovascular coupling (NVC) have been recognized as one of the earliest functional alterations occurring during cSVD. Cerebral functional magnetic resonance imaging (fMRI) is a brain imaging technique that measures the activity of brain areas in vivo by detecting local changes in blood flow. An important advantage of blood oxygen level-dependent functional MRI is that it enables the NVC to be probed in vivo, safely and repeatedly in humans. Our central hypothesis is that functional MRI can provide such a biomarker for monitoring CNV disease progression in vivo using a dedicated fMRI protocol that can be used on a clinical MRI scanner, is reproducible and varies according to the severity of brain MRI lesions and/or clinical manifestations in CADASIL. A functional imaging study coupled with electroencephalogram has already revealed changes in the hemodynamic response to visual or motor stimuli in patients at the early stage of the disease. This study is exploring new imaging protocols to focus on the purest vascular response.