CADASILfMRI BioSVDNCT06859658
Development and Validation of a Functional MRI Biomarker of Cerebral Small Vessel Dysfunction in CADASIL
An observational study of CADASIL, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- CADASIL
- What is being tested?
- Functional MRI at 3T
- Type of treatment
- Surgery or procedure
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2025to 1 Apr 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Patients with a known mutation in the NOTCH3 gene
Who may be able to join
- For CADASIL patients
- Age between 18 and 80 at the time of inclusion
- Diagnosis confirmed by detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL.
- Beneficiaries of a health insurance.
- Written consent.
- For controls:
Show all 9Show fewer
- Age between 18 and 80 at the time of inclusion
- Beneficiary of a health insurance.
- Written consent
Who cannot join
- For patients
- Contraindication to MRI examination
- Disability: Rankin score ≥ 4
- Moderate to severe dementia according to DSM 5 criteria or MMSE score ≤ 19
- Person covered by articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the French Public Health Code, defined by :
- Pregnant, parturient or breast-feeding woman
Show all 32Show fewer
- Person deprived of liberty by judicial or administrative decision.
- Persons hospitalized without consent and not under legal protection, and persons admitted to a health or social establishment for purposes other than research.
- Minor
- Person of full age subject to a legal protection measure (guardianship, curatorship or safeguard of justice), person of full age unable to give consent and not subject to a protection measure.
- Person subject to a period of exclusion for another research project
- For controls :
- Contraindication to MRI examination
- Known cognitive complaint or deficit
- Presence of significant disability (mRS >1)
- Focal neurological motor, sensory or visual deficit on clinical examination that may impair visual or motor stimulation tests
- History of neurological or psychiatric disease
- History of migraine attacks with aura
- Vascular history (known disease of peripheral arteries, heart or brain)
- Known or treated diabetes
- Known or treated hypercholesterolemia
- Known or treated hypertension
- Active smoking or smoking cessation within the last year
- Regular alcohol consumption corresponding to > 2 glasses/day for men and 1 glass/day for women in wine equivalent
- Treatment likely to interfere with neurovascular coupling (in particular any treatment with non-steroidal anti-inflammatory drugs, psychotropic drug(s), antihypertensive drug(s) or statins)
- Person covered by articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the French Public Health Code, defined by :
- Pregnant, parturient or breast-feeding woman
- Person deprived of liberty by judicial or administrative decision
- Persons hospitalized without consent and not under legal protection, and persons admitted to a health or social institution for purposes other than research.
- Minor
- Person of full age subject to a legal protection measure (guardianship, curatorship or safeguard of justice), person of full age unable to give consent and not subject to a protection measure.
- Person subject to a period of exclusion for another research project
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Développement et Validation d'un Biomarqueur en IRM Fonctionnelle de la Dysfonction Des Petits Vaisseaux cérébraux Dans la Maladie de 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.
Read more
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.
- Conditions
- CADASIL
- Being tested
- Functional MRI at 3T
- Keywords
- fMRI, Cerebral Small Vessel Diseases, Neurovascular coupling, CADASIL, Biomarkers
- Medical subject headings
- CADASIL, Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional MRI at 3TRadiation
At inclusion
Functional MRI at 3TRadiation
At inclusion and at 2 years for CADASIL patients without severe disability (mRS<4)
Functional MRI at 3TRadiation
At inclusion and at 2 years for CADASIL patients without severe disability (mRS<4)
| Study group | Role | What they receive |
|---|---|---|
| Control group | Not described Receives: Radiation: Functional MRI at 3T | |
| CADASIL patients with no disability or significant cognitive deficit | Not described Receives: Radiation: Functional MRI at 3T | |
| CADASIL Patients with mild to moderate disability or with a moderate cognitive deficit | Not described Receives: Radiation: Functional MRI at 3T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variation in BOLD response
Variation in BOLD response on functional MRI during short-duration visual stimuli (area under the curve) and parameters derived from this response curve at the calcarine scissure For all patients and controls
Measured: At inclusion
Variation in BOLD response
Variation in BOLD response on functional MRI during short-duration visual stimuli (area under the curve) and parameters derived from this response curve at the calcarine scissure For CADASIL patients
Measured: At 2 years
Secondary outcomes (11)
Correlations between parameters derived from the response curve and age
Measured: Up to 2 years
Correlations between parameters derived from the response curve and gender
Measured: Up to 2 years
Correlations between parameters derived from the response curve and cardiovascular risk factors
Measured: Up to 2 years
Correlations between parameters derived from the response curve and modified Rankin score
Measured: Up to 2 years
Correlations between parameters derived from the response curve and stroke frequency
Measured: Up to 2 years
Correlations between parameters derived from the response curve and stroke number
Measured: Up to 2 years
Correlations between parameters derived from the response curve and total brain volume
Measured: Up to 2 years
Correlations between parameters derived from the response curve and cerebral parenchymal fraction
Measured: Up to 2 years
Correlations between parameters derived from the response curve and normalized WMH (White matter hyperintensity)volume
Measured: Up to 2 years
Correlations between parameters derived from the response curve and number of microbleeds
Measured: Up to 2 years
Correlations between parameters derived from the response curve and number of lacunae
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2025
- Study start1 Apr 2025 (estimated)
- Primary completion1 Apr 2029 (estimated)
- Study completion1 Apr 2029 (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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 70 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
- NCT06859658
- Sponsor's protocol ID
- APHP240772
- Acronym
- fMRI BioSVD
- Status last verified
- Feb 2025
- First submitted
- 28 Feb 2025
- Last updated
- 5 Mar 2025
- 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 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Développement et Validation d'un Biomarqueur en IRM Fonctionnelle de la Dysfonction Des Petits Vaisseaux cérébraux Dans la Maladie de CADASIL
- ClinicalTrials.gov ID
- NCT06859658
- Acronym / sponsor ID
- fMRI BioSVD / APHP240772
- Conditions
- CADASIL
- Keywords
- fMRI, Cerebral Small Vessel Diseases, Neurovascular coupling, CADASIL, Biomarkers
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Apr 2025 (estimated)
- Primary completion
- 1 Apr 2029 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 5 Mar 2025 (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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control group | – | Radiation: Functional MRI at 3T |
| CADASIL patients with no disability or significant cognitive deficit | – | Radiation: Functional MRI at 3T |
| CADASIL Patients with mild to moderate disability or with a moderate cognitive deficit | – | Radiation: Functional MRI at 3T |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a known mutation in the NOTCH3 gene
Key inclusion criteria (9 listed)
- For CADASIL patients
- Age between 18 and 80 at the time of inclusion
- Diagnosis confirmed by detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL.
- Beneficiaries of a health insurance.
- Written consent.
Key exclusion criteria (32 listed)
- For patients
- Contraindication to MRI examination
- Disability: Rankin score ≥ 4
- Moderate to severe dementia according to DSM 5 criteria or MMSE score ≤ 19
- Person covered by articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the French Public Health Code, defined by :
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 |
|---|---|---|
| Functional MRI at 3TAt inclusion | Radiation | Control group |
| Functional MRI at 3TAt inclusion and at 2 years for CADASIL patients without severe disability (mRS<4) | Radiation | CADASIL patients with no disability or significant cognitive deficit |
| Functional MRI at 3TAt inclusion and at 2 years for CADASIL patients without severe disability (mRS<4) | Radiation | CADASIL Patients with mild to moderate disability or with a moderate cognitive deficit |
Primary outcome
Variation in BOLD response
Time frame: At inclusion
Variation in BOLD response on functional MRI during short-duration visual stimuli (area under the curve) and parameters derived from this response curve at the calcarine scissure For all patients and controls
Variation in BOLD response
Time frame: At 2 years
Variation in BOLD response on functional MRI during short-duration visual stimuli (area under the curve) and parameters derived from this response curve at the calcarine scissure For CADASIL patients
11 secondary outcomes
Correlations between parameters derived from the response curve and age
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and gender
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and cardiovascular risk factors
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and modified Rankin score
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and stroke frequency
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and stroke number
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and total brain volume
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and cerebral parenchymal fraction
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and normalized WMH (White matter hyperintensity)volume
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and number of microbleeds
Time frame: Up to 2 years
Correlations between parameters derived from the response curve and number of lacunae
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- 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
RecruitingObservational study
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
Cerebrovascular Disease, Ischemic Stroke
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.
Questions about this trial
What is this clinical trial studying?
An observational study of CADASIL, run by Assistance Publique - Hôpitaux de Paris.
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 9 inclusion and 32 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: opening soon, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hugues Chabriat, MD PhD (+33 1 49 95 25 93 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?
Variation in BOLD response (time frame: At inclusion). The study lists 2 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 5 Mar 2025.