Development of New Biomarkers With Magnetic Resonance Imaging for Longitudinal Studies in CADASIL Angiopathy

Brief Title

Development of New Biomarkers With Magnetic Resonance Imaging for Longitudinal Studies in CADASIL Angiopathy

Official Title

Développement de Nouveaux Biomarqueurs en Imagerie Par résonance magnétique Pour Les études Longitudinales Dans l'Angiopathie CADASIL

Brief Summary

      CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy) is an cerebral microangiopathy secondary to mutations in the NOTCH3 gene
      located on chromosome 19. This disease is the most frequent of the hereditary vascular
      leukoencephalopathies.

      CADASIL begins between the ages of 20 and 40 with the appearance of hyper-signs of brain
      white matter visible on T2 sequences in magnetic resonance imaging (MRI). Before the age of
      30, patients are most often asymptomatic. The disease is then responsible for different
      neurological manifestations:

        1. Migraine attacks with aura occur on average in one in three patients, most often at the
           beginning of the course of the disease, sometimes even before the appearance of MRI
           abnormalities;

        2. Transient ischemic strokes or strokes associated with small cerebral infarcts occur most
           frequently after the age of 50-60 years in more than two out of three patients;

        3. Mood disorders are reported by one in three patients in the same age group;

        4. Cognitive disorders that affect executive functions, especially after the age of 60,
           until the stage of severe dementia associated with walking disorders are observed during
           the course of the disease.

      To date, there is no treatment whose efficacy has been proven in CADASIL. Various studies
      have shown that the accumulation of the most destructive brain tissue lesions at the
      subcortical level was closely correlated in CADASIL with the clinical severity of patients
      (motor and cognitive disability). It is now possible to measure microstructural changes in
      brain tissue in diffusion imaging during the course of the disease, even before significant
      clinical changes are detected.
    



Study Type

Observational


Primary Outcome

Intra-axonal


Condition

Cadasil

Intervention

Cerebral Magnetic resonance imaging (MRI)

Study Arms / Comparison Groups

 Patients
Description:  Patients with CADASIL disease : Diagnosis confirmed by the detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

80

Start Date

August 10, 2019

Completion Date

January 6, 2023

Primary Completion Date

July 6, 2022

Eligibility Criteria

        Inclusion Criteria:

        Patients

          -  Age from 18 to 80 years

          -  Confirmed diagnosis (detection of a pathogenic mutation of the NOTCH3 gene)

          -  Detailed clinical and MRI assessment of the disease (follow-up at the CERVCO)
             including Rankin score <4

          -  Any contraindication to MRI or EEG examination (claustrophobia, presence of material
             with magnetic properties)

          -  Social security insurance

          -  Written consent.

        Controls

          -  Age from 18 to 80 years

          -  No history of neurological or psychiatric diseases

          -  No history of migraine with aura

          -  No history of vascular disease (peripheral arteries, heart, brain)

          -  No known or treated diabetes

          -  No known or treated hypercholesterolemia

          -  Social security insurance

          -  Written consent

        Exclusion Criteria:

        Patients

          -  Patients with a contraindication to MRI or EEG examination (claustrophobia, material
             with magnetic properties: pacemaker, ferromagnetic material ...)

          -  For MRI examination of neurovascular coupling: Patients with a treatment that may
             interfere with neurovascular coupling (in particular any treatment with non-steroidal
             anti-inflammatory drugs, psychotropic drugs, antihypertensive agents or statins)

          -  Patients without a social security insurance

          -  Patients under the age of 18 or over 80 at the time of the first visit

          -  Patients unable to give their informed consent

          -  Person referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the Public
             Health Code, defined by:

               -  Pregnant, parturient or nursing woman

               -  Person deprived of liberty by judicial or administrative decision

               -  Person hospitalized without consent and not subject to a legal protection
                  measure, and person admitted to a health or social institution for purposes other
                  than research

               -  Minor

               -  Adult under legal protection measure (guardianship, guardianship or court order),
                  an adult unable to express their consent and not subject to a protective measure

               -  Person submitted to an exclusion period for another research (washout period)

        Controls

          -  Subject with a contraindication to MRI or EEG examination (claustrophobia, material
             with magnetic properties: pacemaker, ferromagnetic material ...)

          -  For MRI examination of neurovascular coupling: Subject with a treatment that may
             interfere with neurovascular coupling (in particular any treatment with non-steroidal
             anti-inflammatory drugs, psychotropic drugs, antihypertensive agents or statins)

          -  Subject without a social security insurance

          -  Subject under the age of 18 or over 80 years at the time of the first visit

          -  Patients unable to give their informed consent

          -  Person referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the Public
             Health Code, defined by:

               -  Pregnant, parturient or nursing woman

               -  Person deprived of liberty by judicial or administrative decision

               -  Person hospitalized without consent and not subject to a legal protection
                  measure, and person admitted to a health or social institution for purposes other
                  than research

               -  Minor

               -  Adult under legal protection measure (guardianship, guardianship or court order),
                  an adult unable to express their consent and not subject to a protective measure

               -  Person submitted to an exclusion period for another research study (washout
                  period)
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, 149952597, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04036084

Organization ID

APHP180325


Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris


Study Sponsor

, , 


Verification Date

July 2020