- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04036084
Development of New Biomarkers With Magnetic Resonance Imaging for Longitudinal Studies in CADASIL Angiopathy (BIOMRI_CADA)
Développement de Nouveaux Biomarqueurs en Imagerie Par résonance magnétique Pour Les études Longitudinales Dans l'Angiopathie CADASIL
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:
- 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;
- 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;
- Mood disorders are reported by one in three patients in the same age group;
- 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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Hugues CHABRIAT, MD, PhD
- Phone Number: +33 149952597
- Email: hugues.chabriat@aphp.fr
Study Locations
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-
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Paris, France, 75010
- Recruiting
- Lariboisière Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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)
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Control
|
Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Inclusion Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Month 1 Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Year 1
|
Patients
Patients with CADASIL disease : Diagnosis confirmed by the detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL
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Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Inclusion Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Month 1 Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Year 1
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Intra-axonal
Time Frame: 1 year
|
Intra-axonal volume fraction
|
1 year
|
Extra-axonal
Time Frame: 1 year
|
Extra-axonal volume fraction
|
1 year
|
Intra-myelinic edema
Time Frame: 1 year
|
Volume fraction of intra-myelinic edema
|
1 year
|
Microvascular compartment fraction measured using diffusion MRI (IVIM)
Time Frame: 1 year
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Measures of the Flowing blood volume fraction (corresponding to slow intra-voxel incoherent motion (IVIM) of water molecules in the cerebral microvasculature at voxel level)
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1 year
|
variation
Time Frame: 1 year
|
Overall variation of cerebral blood flow over 20 and 40 seconds stimulations (area under a curve)
|
1 year
|
blood flow
Time Frame: 1 year
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Maximum cerebral blood flow measured over 20 and 40 seconds stimulations
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1 year
|
Slope
Time Frame: 1 year
|
Slope of the regression curve when cerebral blood flow is measured 15 and 35 seconds after the onset of the stimulation
|
1 year
|
Dynamics of the cerebral blood
Time Frame: 1 year
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Dynamics of the cerebral blood flow curve between 15 and 35 seconds (model with dual component responses; fast (before 20 seconds) and slow (after 20 seconds))
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1 year
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Ischemia
- Pathologic Processes
- Necrosis
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Brain Ischemia
- Dementia
- Infarction
- Stroke
- Brain Infarction
- Cerebral Arterial Diseases
- Intracranial Arterial Diseases
- Cerebral Small Vessel Diseases
- Cerebral Infarction
- Dementia, Vascular
- CADASIL
- Dementia, Multi-Infarct
Other Study ID Numbers
- APHP180325
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cadasil
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National Heart, Lung, and Blood Institute (NHLBI)CompletedCardiovascular Disease | Arterial Stiffness | Germline Mutation in the NOTCH 3 Gene | Pathogenesis of CADASIL | Clinical Phenotype of CADASILUnited States
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National Heart, Lung, and Blood Institute (NHLBI)RecruitingCardiovascular Disease | Arterial Stiffness | Germline Mutation in the NOTCH 3 Gene | Pathogenesis of CADASIL | Clinical Phenotype of CADASILUnited States
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National Cerebral and Cardiovascular Center, JapanCompleted
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Peking University First HospitalChinese Academy of SciencesRecruiting
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