Cerebral Amyloid Aβ AngiopathyGENERALITY2NCT06864000
Phenotypic and Molecular Characterisation of Cerebral Amyloid Angiopathy
An observational study of Cerebral Amyloid Aβ Angiopathy, run by University Hospital, Rouen at 1 site in France.
Trial summary
Cerebral Aβ amyloid angiopathy is a severe disease characterised by amyloid deposits in the cerebral vessels, manifested mainly by recurrent cerebral haematomas and cognitive impairment. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Cerebral Amyloid Aβ Angiopathy
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 31 Mar 2023to 30 Dec 2027
- How long will I take part?
- 6 Months
- 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 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Etude proposée aux patients adultes atteints d'angiopathie amyloïde cérébrale pour lesquels un prélèvement sanguin est prévu au titre du diagnostic dans le cadre du soin
Who may be able to join
- Patients with a diagnosis of cerebral amyloid angiopathy (CAA) whose genetic samples are initially sent to the Rouen or Paris-Lariboisière genetics laboratories for molecular diagnosis of a genetic cause, thanks to national recruitment and for whom the patients consent to continuing genetic analyses for research purposes without feedback.
- Diagnosis of cerebral amyloid angiopathy (CAA) certain or probable according to the modified Boston diagnostic criteria (1) (except age)
- Age of onset of symptoms <66 years
- Absence of APP mutation/duplication (analysis must already have been carried out in the laboratory on receipt of the sample as part of routine care)
- Signed consent for research
- Patient covered by a social security scheme
Who cannot join
- Age at first neurological symptom > 66 years
- Minor patients
- Other differential diagnosis that better explains the clinical situation
- Identification of mutations or duplication of the APP gene
- AAC possible but not probable according to the revised Boston criteria
- Patient deprived of liberty by judicial or administrative decision
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
University Hospital Rouen
Rouen, 76031
Lou LG GRANGEON, Doctor, 02 32 88 37 90 ext. +33, Lou.grangeon@chu-rouen.fr
About this study
Official title: Phenotypic and Molecular Characterisation of Early-onset Cerebral Amyloid Angiopathy
Cerebral Aβ amyloid angiopathy is a severe disease characterised by amyloid deposits in the cerebral vessels, manifested mainly by recurrent cerebral haematomas and cognitive impairment. Diagnostic criteria are based on brain imaging, but the usefulness of this imaging in predicting the course of the disease remains undetermined. The genetic component is largely understudied. Less than 5% of patients carry mutations or duplications of the APP gene. Susceptibility factors such as APOE genotypes and rare variants recently discovered in Alzheimer's disease within the SORL1, TREM2 or ABCA7, ABCA1 and ATP8B4 genes could play a role in the pathophysiology of cerebral amyloid angiopathy. There is currently no specific treatment available. Based on a national recruitment of patients with cerebral amyloid angiopathy, this project aims to assess the role of genetic variants in the diagnosis and progression of cerebral amyloid angiopathy. A better understanding of the mechanisms, particularly genetic, could help us to develop treatments in the era of gene therapy.
Read the detailed description
This research is carried out on the same blood sample taken during the treatment and sent to the Rouen University Hospital Genetics Laboratory for research into point mutations or duplication of the APP gene as part of the diagnosis of cerebral amyloid angiopathy (CAA). For each gene, the proportions of variant carriers will be compared between cases and controls using a Fisher exact test with R statistical software. To rule out any population stratification bias, the tests will also be carried out using logistic regression adjusted on the first PCA axes (principal component analysis) using the seqmeta function. A Bonferroni correction will then be used to adjust the significance threshold according to the number of genes tested.
- Conditions
- Cerebral Amyloid Aβ Angiopathy
- Keywords
- Phenotypic and molecular characterisation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| FREX (French Exome Project) control cohort group | Control cohort corresponding to the FREX cohort (French Exome Project) including 585 exomes of healthy individuals (from 6 French regions) and whose data is already available to research groups for case-control association analysis. | |
| Group of patients with cerebral amyloid angiopathy (CAA) | Patients with APOE4 genetic risk factors and rare variants of SORL1, TREM2, ABCA7, ABCA1 and ATP8B4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
patients with APOE4 genetic risk factors
Define the proportion of patients with APOE4 genetic risk factors (%) in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
Measured: 1 day
patients with rare variants of SORL1
Define the proportion of patients with rare variants (%) of SORL1, in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
Measured: 1 day
patients with rare variants of TREM2
Define the proportion of patients with rare variants (%) of TREM2 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
Measured: 1 day
patients with rare variants of ABCA7
Define the proportion of patients with rare variants (%) of ABCA7 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
Measured: 1 day
patients with rare variants of ABCA1
Define the proportion of patients with rare variants (%) of ABCA1 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
Measured: 1 day
patients with rare variants of ATP8B4
Define the proportion of patients with rare variants (%) of ATP8B4 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
Measured: 1 day
Secondary outcomes (6)
Genotype/clinical phenotype correlations
Establish genotype/clinical phenotype correlations concerning the age of onset, the severity of the disease and the risk of recurrence of haematomas (identified during follow-up visits at M6 and M12 as part of routine care).
Measured: 12 months
Biological characterisation of AACs (Aβ42,CSF biomarkers)
- assessment of the diagnostic value of assays for Aβ42 biomarkers currently validated in Alzheimer's disease and related neurocognitive disorders
Measured: 12 months
Biological characterisation of AACs (Aβ40, CSF biomarkers)
- assessment of the diagnostic value of assays for Aβ40, CSF biomarkers currently validated in Alzheimer's disease and related neurocognitive disorders
Measured: 12 months
Imaging characterisation of AACs (topography of cerebral bleeds)
- identification of biomarker profiles linked to the topography of cerebral bleeds
Measured: 12 months
Imaging characterisation of AACs (typology of cerebral bleeds)
- identification of biomarker profiles linked to the typology of cerebral bleeds
Measured: 12 months
Imaging characterisation of AACs (distribution of cerebral bleeds)
- identification of biomarker profiles linked to the distribution of cerebral bleeds
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2025
- Study start31 Mar 2023
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Amyloid Aβ AngiopathyStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe 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
- 100 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lou LG GRANGEON, Doctor, Principal investigator, University Rouen Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06864000
- Sponsor's protocol ID
- 2022/0241/OB
- Other IDs
- 2022-A02248-35
- Acronym
- GENERALITY2
- Status last verified
- Feb 2025
- First submitted
- 26 Feb 2025
- Last updated
- 7 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data provided will be the property of the sponsor and will be used solely for its own research activities.
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypic and Molecular Characterisation of Early-onset Cerebral Amyloid Angiopathy
- ClinicalTrials.gov ID
- NCT06864000
- Acronym / sponsor ID
- GENERALITY2 / 2022/0241/OB
- Conditions
- Cerebral Amyloid Aβ Angiopathy
- Keywords
- Phenotypic and molecular characterisation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 31 Mar 2023 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 7 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 Aβ amyloid angiopathy is a severe disease characterised by amyloid deposits in the cerebral vessels, manifested mainly by recurrent cerebral haematomas and cognitive impairment. Diagnostic criteria are based on brain imaging, but the usefulness of this imaging in predicting the course of the disease remains undetermined. The genetic component is largely understudied. Less than 5% of patients carry mutations or duplications of the APP gene. Susceptibility factors such as APOE genotypes and rare variants recently discovered in Alzheimer's disease within the SORL1, TREM2 or ABCA7, ABCA1 and ATP8B4 genes could play a role in the pathophysiology of cerebral amyloid angiopathy. There is currently no specific treatment available. Based on a national recruitment of patients with cerebral amyloid angiopathy, this project aims to assess the role of genetic variants in the diagnosis and progression of cerebral amyloid angiopathy. A better understanding of the mechanisms, particularly genetic, could help us to develop treatments in the era of gene therapy.
Detailed description
This research is carried out on the same blood sample taken during the treatment and sent to the Rouen University Hospital Genetics Laboratory for research into point mutations or duplication of the APP gene as part of the diagnosis of cerebral amyloid angiopathy (CAA). For each gene, the proportions of variant carriers will be compared between cases and controls using a Fisher exact test with R statistical software. To rule out any population stratification bias, the tests will also be carried out using logistic regression adjusted on the first PCA axes (principal component analysis) using the seqmeta function. A Bonferroni correction will then be used to adjust the significance threshold according to the number of genes tested.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FREX (French Exome Project) control cohort group | – | –Control cohort corresponding to the FREX cohort (French Exome Project) including 585 exomes of healthy individuals (from 6 French regions) and whose data is already available to research groups for case-control association analysis. |
| Group of patients with cerebral amyloid angiopathy (CAA) | – | –Patients with APOE4 genetic risk factors and rare variants of SORL1, TREM2, ABCA7, ABCA1 and ATP8B4 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Etude proposée aux patients adultes atteints d'angiopathie amyloïde cérébrale pour lesquels un prélèvement sanguin est prévu au titre du diagnostic dans le cadre du soin
Key inclusion criteria (6 listed)
- Patients with a diagnosis of cerebral amyloid angiopathy (CAA) whose genetic samples are initially sent to the Rouen or Paris-Lariboisière genetics laboratories for molecular diagnosis of a genetic cause, thanks to national recruitment and for whom the patients consent to continuing genetic analyses for research purposes without feedback.
- Diagnosis of cerebral amyloid angiopathy (CAA) certain or probable according to the modified Boston diagnostic criteria (1) (except age)
- Age of onset of symptoms <66 years
- Absence of APP mutation/duplication (analysis must already have been carried out in the laboratory on receipt of the sample as part of routine care)
- Signed consent for research
Key exclusion criteria (6 listed)
- Age at first neurological symptom > 66 years
- Minor patients
- Other differential diagnosis that better explains the clinical situation
- Identification of mutations or duplication of the APP gene
- AAC possible but not probable according to the revised Boston criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
patients with APOE4 genetic risk factors
Time frame: 1 day
Define the proportion of patients with APOE4 genetic risk factors (%) in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
patients with rare variants of SORL1
Time frame: 1 day
Define the proportion of patients with rare variants (%) of SORL1, in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
patients with rare variants of TREM2
Time frame: 1 day
Define the proportion of patients with rare variants (%) of TREM2 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
patients with rare variants of ABCA7
Time frame: 1 day
Define the proportion of patients with rare variants (%) of ABCA7 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
patients with rare variants of ABCA1
Time frame: 1 day
Define the proportion of patients with rare variants (%) of ABCA1 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
patients with rare variants of ATP8B4
Time frame: 1 day
Define the proportion of patients with rare variants (%) of ATP8B4 in patients with early-onset cerebral amyloid angiopathy (CAA) (<66 years) and patients with causal mutations in the PSEN1 and PSEN2 genes.
6 secondary outcomes
Genotype/clinical phenotype correlations
Time frame: 12 months
Biological characterisation of AACs (Aβ42,CSF biomarkers)
Time frame: 12 months
Biological characterisation of AACs (Aβ40, CSF biomarkers)
Time frame: 12 months
Imaging characterisation of AACs (topography of cerebral bleeds)
Time frame: 12 months
Imaging characterisation of AACs (typology of cerebral bleeds)
Time frame: 12 months
Imaging characterisation of AACs (distribution of cerebral bleeds)
Time frame: 12 months
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 7 Mar 2025.
- Individual participant dataSharing planned: No. The data provided will be the property of the sponsor and will be used solely for its own research activities.
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.
Lou LG GRANGEON, Doctor principal investigator
University Rouen Hospital
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 Cerebral Amyloid Aβ Angiopathy, run by University Hospital, Rouen 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 6 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 7 Mar 2025. 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?
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 David DM MALLET, Director (+33 2 32 88 82 65, Secretariat.DRC@chu-rouen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
patients with APOE4 genetic risk factors (time frame: 1 day). The study lists 6 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 7 Mar 2025.