Status unknownNCT04036084BIOMRI_CADAUpdated Aug 18, 2020

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

An observational study in Cadasil and Angiopathy; Cerebral, sponsored by Assistance Publique - Hôpitaux de Paris. Status unknown at 1 site in France. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-08-18.

Sponsored by Assistance Publique - Hôpitaux de Paris · Observational

The sponsor has not verified this record recently (last verified Jul 2020), so the status shown — last known as Recruiting — may be out of date.

Study type: Observational
Model: Cohort
Time perspective: Prospective
Enrollment: 80
Ages: 18 Years to 80 Years
Sex: All

Study 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:

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.

Conditions studied

Cadasil
Angiopathy; Cerebral

Browse trials for

CADASIL 36

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: Yes
Sampling method: Probability sample

Study population

CADASIL patients with a proven NOTCH3 mutation

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

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 design

Observational model: Cohort
Time perspective: Prospective
Enrollment: 80 participants (estimated)
Patient registry: No

Groups and cohorts

Patients
Patients with CADASIL disease : Diagnosis confirmed by the detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL
Diagnostic Test: Cerebral Magnetic resonance imaging (MRI)
Control
Diagnostic Test: Cerebral Magnetic resonance imaging (MRI)

Interventions

Diagnostic testCerebral Magnetic resonance imaging (MRI)
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

What researchers measure

Primary outcomes

Intra-axonal
Intra-axonal volume fraction
Time frame: 1 year
Extra-axonal
Extra-axonal volume fraction
Time frame: 1 year
Intra-myelinic edema
Volume fraction of intra-myelinic edema
Time frame: 1 year
Microvascular compartment fraction measured using diffusion MRI (IVIM)
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)
Time frame: 1 year
variation
Overall variation of cerebral blood flow over 20 and 40 seconds stimulations (area under a curve)
Time frame: 1 year
blood flow
Maximum cerebral blood flow measured over 20 and 40 seconds stimulations
Time frame: 1 year
Slope
Slope of the regression curve when cerebral blood flow is measured 15 and 35 seconds after the onset of the stimulation
Time frame: 1 year
Dynamics of the cerebral blood
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))
Time frame: 1 year

Study locations

1 of 1 sites recruiting

Lariboisiere hospital
Paris, 75010, France
- Nathalie GASTELLIER, PhD · Contact · nathalie.gastellier@aphp.fr · 149956872
- matthieu RESCHE-RIGON, MD-PhD · Contact · matthieu.resche-rigon@univ-paris-diderot.fr · 142499742
Recruiting

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

Registry details

Key details

Study ID: NCT04036084
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Responsible party: Sponsor
First posted: Jul 29, 2019
Start date: Aug 10, 2019
Primary completion: Jul 6, 2022 (estimated)
Completion: Jan 6, 2023 (estimated)
Last update: Aug 18, 2020

Study contacts

Hugues CHABRIAT, MD, PhD

Contact

hugues.chabriat@aphp.fr

149952597 ext. +33

Nathalie GASTELLIER, PhD

Contact

nathalie.gastellier@aphp.fr

149956872 ext. +33

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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