CadasilBIOMRI_CADANCT04036084
Development of New Biomarkers With Magnetic Resonance Imaging for Longitudinal Studies in CADASIL Angiopathy
An observational study of Cadasil and Angiopathy; Cerebral, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Cadasil, Angiopathy; Cerebral
- What is being tested?
- Cerebral Magnetic resonance imaging (MRI)
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- 10 Aug 2019to 6 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: CADASIL patients with a proven NOTCH3 mutation
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Lariboisiere hospital
Paris, 75010
Nathalie GASTELLIER, PhD, 149956872 ext. +33, nathalie.gastellier@aphp.fr
matthieu RESCHE-RIGON, MD-PhD, 142499742 ext. +33, matthieu.resche-rigon@univ-paris-diderot.fr
About this study
Official title: 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:
Read more
- 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
- Cadasil, Angiopathy; Cerebral
- Being tested
- Cerebral Magnetic resonance imaging (MRI)
- Medical subject headings
- CADASIL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cerebral Magnetic resonance imaging (MRI)Diagnostic test
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
| Study group | Role | What they receive |
|---|---|---|
| Patients | Patients with CADASIL disease : Diagnosis confirmed by the detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL Receives: Diagnostic Test: Cerebral Magnetic resonance imaging (MRI) | |
| Control | Not described Receives: Diagnostic Test: Cerebral Magnetic resonance imaging (MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-axonal
Intra-axonal volume fraction
Measured: 1 year
Extra-axonal
Extra-axonal volume fraction
Measured: 1 year
Intra-myelinic edema
Volume fraction of intra-myelinic edema
Measured: 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)
Measured: 1 year
variation
Overall variation of cerebral blood flow over 20 and 40 seconds stimulations (area under a curve)
Measured: 1 year
blood flow
Maximum cerebral blood flow measured over 20 and 40 seconds stimulations
Measured: 1 year
Slope
Slope of the regression curve when cerebral blood flow is measured 15 and 35 seconds after the onset of the stimulation
Measured: 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))
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2019
- Study start10 Aug 2019
- Primary completion6 Jul 2022 (estimated)
- Study completion6 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CadasilStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04036084
- Sponsor's protocol ID
- APHP180325
- Acronym
- BIOMRI_CADA
- Status last verified
- Jul 2020
- First submitted
- 15 Jul 2019
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Développement de Nouveaux Biomarqueurs en Imagerie Par résonance magnétique Pour Les études Longitudinales Dans l'Angiopathie CADASIL
- ClinicalTrials.gov ID
- NCT04036084
- Acronym / sponsor ID
- BIOMRI_CADA / APHP180325
- Conditions
- Cadasil, Angiopathy; Cerebral
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 10 Aug 2019 (actual)
- Primary completion
- 6 Jul 2022 (estimated)
- Study completion
- 6 Jan 2023 (estimated)
- First posted
- 29 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Diagnostic Test: Cerebral Magnetic resonance imaging (MRI)Patients with CADASIL disease : Diagnosis confirmed by the detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL |
| Control | – | Diagnostic Test: Cerebral Magnetic resonance imaging (MRI) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- CADASIL patients with a proven NOTCH3 mutation
Key inclusion criteria (16 listed)
- 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)
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cerebral 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 | Diagnostic test | Control, Patients |
Primary outcome
Intra-axonal
Time frame: 1 year
Intra-axonal volume fraction
Extra-axonal
Time frame: 1 year
Extra-axonal volume fraction
Intra-myelinic edema
Time frame: 1 year
Volume fraction of intra-myelinic edema
Microvascular compartment fraction measured using diffusion MRI (IVIM)
Time frame: 1 year
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)
variation
Time frame: 1 year
Overall variation of cerebral blood flow over 20 and 40 seconds stimulations (area under a curve)
blood flow
Time frame: 1 year
Maximum cerebral blood flow measured over 20 and 40 seconds stimulations
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
Dynamics of the cerebral blood
Time frame: 1 year
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))
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2020.
- Individual participant dataSharing planned: Undecided
Related trials for Cadasil
RecruitingObservational study
Registry for CADASIL
Cerebral Autosomal Dominant Ateriopathy With Subcortical Infarcts and Leukoencephalopathy
RecruitingObservational study
Natural History Study of CADASIL
Cardiovascular Disease, Arterial Stiffness
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The Erlanger Stroke Registry (ESPro) is the Only Ongoing Prospective Population-based Stroke Registry in Germany, Started in 1994. ESPro Includes All Hospitalized and Non-hospitalized Patients With Stroke in the Community of Erlangen (120.000 Inhabitants), With a Long-life Follow-up.
Intracerebral Haemorrhage (ICH), Cerebral Infarction
Active, not recruitingObservational study
Florida Cerebrovascular Disease Biorepository and Genomics Center
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RecruitingObservational study
Effect of the Mediterranean Diet in Patients Affected by CADASIL and Cerebral Amyloid Angiopathy.
Cerebral Amyloid Angiopathy, CAA - Cerebral Amyloid Angiopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cadasil and Angiopathy; Cerebral, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hugues CHABRIAT, MD, PhD (149952597 ext. +33, hugues.chabriat@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intra-axonal (time frame: 1 year). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2020.