Alzheimer Disease, Early OnsetPET-ALNCT04150198
MECHANISMS OF NEURONAL RESILIENCE IN ALZHEIMER'S DISEASE AND ITS FOCAL VARIANTS: A PET/MR STUDY
A study testing TEP/IRM in people with Alzheimer Disease, Early Onset and Posterior Cortical Atrophy, run by Institut National de la Santé Et de la Recherche Médicale, France at 2 sites in France.
Trial summary
Patients with Alzheimer's disease and with early onset of symptoms (<65 years) (AD-Y) have a multi-domain cognitive deficit, whereas memory disorders (typical of the elderly patient's AD) are less often in the foreground. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Early Onset, Posterior Cortical Atrophy
- What is being tested?
- TEP/IRM
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 2 sitesFrance
- Study dates
- 8 Dec 2021to 31 Dec 2029
- Phase
- Interventional
- 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 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- For all subjects:
- Affiliation to a social security insurance or beneficiary
- Informed consent form signed by the participant or his / her legal representative
- Participants aged 40 to 80 years.
- Selection of AD-Y group
- In vivo proof of Alzheimer's pathology:
Show all 45Show fewer
- Determination of specific proteins on the cerebrospinal fluid (CSF, a routine care procedure). The values considered pathological (AD) are Aβ1-42 peptide <500 (μg / ml), and / or tau protein> 450 and phosphorylated tau protein> 60, IATI index <1, tau / Aβ protein ratios > 1.23 as well as phosphorylated tau protein / Aβ1-42> 0.211.
- And / or a positive PET-amyloid imaging test.
- Early-onset episodic memory deficit (<65 years), progressive onset with evidence of hippocampal amnesic syndrome at neuropsychological assessment.
- In memory tests, the amnesic hippocampal syndrome is defined by: a deficit of the free recall despite a reinforced encoding, an effectiveness of the indexing or an impairment of the recognition capabilities, the presence of intrusions. The presence during the tests of false memories spontaneous (intrusions) or provoked (false recognitions) is also very contributive to the definition of amnesic syndrome of the hippocampal type.
- PCA group selection
- Patients with a clinical and cognitive profile suggestive of PCA, characterized by:
- an in vivo proof of the Alzheimer pathology (see selection of the AD-Y group)
- a specific impairment of neuro-visual abilities, in the absence of major disorders of episodic memory (hippocampal) and executive functions.
- Two possible variants:
- occipito-temporal variant: visuo-perceptive deficit in the foreground, early onset and progressive worsening; lack of visual identification of objects, symbols, words or faces;
- biparietal variant: visuospatial deficit in the foreground, early settlement and progressive worsening; Gerstmann syndrome; Balint syndrome; gestural apraxia; visual-spatial neglect.
- Selection of the control subjects group
- Normal neurological and neuropsychological examinations.
- Control subjects will be matched in age to patients.
- Non-inclusion Criteria:
- General non-inclusion criteria:
- Medical history of torsade de pointe or risk of torsade de pointes
- Patient treated with drugs known to lengthen QT (see www.crediblemeds.org)
- Contraindication to radiopharmaceutical injection:
- For precautions of safety of use of the radiopharmaceutical, a blood sample allowing to check the renal and hepatic functions will be realized before imagery. The delay between the sampling and the neuroimaging visit is left to the investigator's discretion based on the patient's biological results. In particular, the glomerular filtration rate will be calculated from the results obtained.
- In the event of renal insufficiency (GFR 30mL / min / 1.73m2), hepatic insufficiency or any other biological anomaly of grade 3 or higher detected during these analyzes, the participant will not be able to carry out PET imaging. In this case, the results of the analyzes will be sent to the doctor indicated by the participant. This evaluation, which involves a determination of serum creatinine, is part of the standard routine biological assessment performed in the context of cognitive disorders
- Inability to provide informed consent by participant or legal representative:
- Patient deprived of liberty by decision of justice or not benefiting from social cover.
- Person in the process of participating in another therapeutic research or in a period of exclusion from another research.
- Participants with a contraindication to MRI: pacemaker or cardiac defibrillator, implanted equipment activated by an electrical, magnetic or mechanical system, haemostatic clips of intracerebral aneurysms or carotid arteries , carriers of orthopedic implants.
- Contraindication to radiopharmaceutical injection: known hypersensitivity to the active substance or to any of the excipients, renal impairment (GFR 30mL / min / 1.73m2), hepatic insufficiency or any other biological abnormality of grade 3 or higher
- Person suffering from claustrophobia.
- Pregnancy (for women of childbearing age, a urine pregnancy test will be performed on the day of the inclusion visit and the PET-MRI examination).
- Any symptoms or biological values suggestive of a systemic disorder (renal, hepatic, cardiovascular, pulmonary) or any other medical conditions that could interfere with the interpretation of test results or compromise the health of patients.
- Person subject to a legal safeguard.
- Specific non-inclusion criteria for AD-Y and PCA patients:
- Sudden appearance of cognitive deficits.
- Gait disturbances, convulsions, major behavior modification.
- Focal alterations to neurological examination, extrapyramidal signs, hallucinations, fluctuations. cognitive.
- Psychiatric, cerebrovascular, metabolic, inflammatory pathology.
- Specific non-inclusion criteria for control subjects:
- Pathological neurological examination
- History of neurological disease (in particular ischemic stroke or neurodegenerative disease) or psychiatric illness (particularly severe depression, psychosis, or bipolar illness still requiring drug treatment at the time of inclusion)
- Physical affection that is serious or can interfere with cognitive functions.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Service Hospitalier Frédéric Joliot SHFJ
Orsay, 91401 cedex
Vincent Pr LEBON, 01.69.86.77.01, vincent.lebon@universite-paris-saclay.fr
Michel Dr BOTTLAENDER, 01.69.86.77.12, michel.bottlaender@cea.fr
- Recruiting
Service de Médecine Nucléaire - Hopital La Pitié Salpetriere
Paris, 75013
Marie Odile, MCU-PH, marie-odile.habert@aphp.fr
About this study
Patients with Alzheimer's disease and with early onset of symptoms (<65 years) (AD-Y) have a multi-domain cognitive deficit, whereas memory disorders (typical of the elderly patient's AD) are less often in the foreground. In addition, some MA-J have an atypical phenotype indicating focal brain damage, although they have the same pathological lesions: amyloid deposits and tau protein deposition (DNF). This is the case of posterior cortical atrophy (PCA) characterized by complex visual disturbances and atrophy affecting the more posterior regions of the brain. Based on the clinical profile of PCA patients, a more refined anatomo-clinical classification was proposed, distinguishing a rather "ventral" form and a rather "dorsal" form. The recent arrival of tau-specific PET tracers now makes it possible to evaluate in vivo fibrillary neurodegeneration (FND), which is well correlated with the severity of cognitive disorders. Advances in MRI have shown that each neurodegenerative syndrome targets a large-scale neural network, which in turn shows a vulnerability for a specific biological disease. In the case of AD, the reason for such a difference in cognitive and anatomical impairment between patients with diffuse involvement and others with more focal involvement is not known. One possible explanation is the existence, in focal forms, of neuronal mechanisms that oppose vulnerability. These mechanisms may correspond to the so-called "resilience" phenomenon, defined as resistance to a neuropathological process by the ability to optimize cognitive performance via the efficient recruitment of neural networks. The mechanisms underlying resilience in neurodegeneration are unknown. Their identification is very important for the management and treatment of AD.
Read the detailed description
Working hypotheses We hypothesize that "focal" patients (PCA) versus "diffuse" patients (AD-Y) have (i) less severe white matter involvement; (ii) effective reorganization of the functional brain networks; iii) pathologically, a different topography and lesion load.
This project has no redundancy with the work already done in our team and in other teams at the international level.
Expected benefits This study will highlight the neural mechanisms underlying resiliency in a group of AD patients who, although having the same disease, present with a very different clinical and cognitive profile. Demonstration of these specific mechanisms of resilience in the diseased brain is essential to better understand the pathophysiological processes of AD. We consider that the pharmacological approach and the functional reeducation to this disease depend essentially on a better knowledge of both the topographic distribution of the underlying histopathology (in particular, the tau protein), and the response capacity from the brain to these lesions (state of connection of networks, functional reorganization). In addition, when treatments for AD are available, a precise definition of phenotypic variants will be essential for the selection of patients for these therapies and for therapeutic follow-up. In the longer term, resilient neural circuits could be modulated and strengthened through transcranial stimulation. Indeed, promising results have been obtained showing that these techniques can improve the performance of altered cognitive functions in patients with dementia.
- Being tested
- TEP/IRM
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEP/IRMDevice
All participants will have a PET / MRI examination including: i) a 30-minute PET scan, 80 minutes after intravenous injection of 240 MBq of 18F-AV1451 ± 10% ii) a ZTE sequence (for attenuation correction of PET images), a 3D T1 anatomical sequence, a diffusion MRI, a functional MRI at rest (total duration: 45 minutes). These acquisitions will be made during the same exam session on a hybrid PET / MRI camera allowing simultaneous acquisitions. This visit lasts about 3 hours.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Alzheimer (<65 years) (AD-Y) | Experimental | 15 patients with a diagnostic of MA-J Receives: Device: TEP/IRM |
| Patients with posterior Cortical Atrophy (PCA) | Experimental | 15 patients with a diagnostic of PCA Receives: Device: TEP/IRM |
| Control | Active comparator | 15 controls Receives: Device: TEP/IRM |
What is being measured
The primary outcome is the main question the study is designed to answer.
highlight of the "resilient" neural networks
For this, we will study:
- The topographic distribution regions of tau lesions, thanks to PET brain imaging using the 18F-AV-1451 as a ligand.
Measured: up to 3 months
quantify the impairment (ie brain vulnerability) in AD-Y and in PCA
For this, we will study:
- The correlation between the distribution of these tau lesions and: the cortical volume, the indices of integrity of the white matter bundles, the functional neural networks, as well as the reorganization of the "hubs" of these networks, thanks to the structural MRI, diffusion (MRI) and functional at rest (fMRI) imaging.2)
Measured: up to 3 months
Secondary outcomes (2)
correlation between the concentration of tau-tauphosphorylated protein in cerebrospinal fluid (CSF) with the lesion load measured in PET
this comparison is a key element of characterization of this new ligand compared to widely validated CSF biomarkers
Measured: up to 3 months
predictive model of functional alterations based on the structural alterations of the gray matter and the white matter.
To establish this correlation the evaluation criterion is represented by the measurement of cortical thickness, the indices of integrity of the beams of the white substance (fractional anisotropy, average, radial and perpendicular diffusivities), as well as the integration values of the functional networks and the distribution of "hubs"
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start8 Dec 2021
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Nombre de participants 45 sujets répartis dans 3 groupes: 1. Groupe MA-J (Maladie d'Alzheimer précoce)= 15 patients avec un diagnostic de MA-J 2. Groupe ACP (Atrophie Corticale Posterieure)= 15 patients avec un diagnostic d'ACP 3. Groupe sujets contrôles= 15 sujets contrôles
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- France Alzheimer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04150198
- Sponsor's protocol ID
- C19-40
- Acronym
- PET-AL
- Status last verified
- Aug 2026
- First submitted
- 22 Oct 2019
- Last updated
- 20 Aug 2026
- 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 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MECHANISMS OF NEURONAL RESILIENCE IN ALZHEIMER'S DISEASE AND ITS FOCAL VARIANTS: A PET/MR STUDY
- ClinicalTrials.gov ID
- NCT04150198
- Acronym / sponsor ID
- PET-AL / C19-40
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- France Alzheimer
- Study start
- 8 Dec 2021 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 4 Nov 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.
Patients with Alzheimer's disease and with early onset of symptoms (<65 years) (AD-Y) have a multi-domain cognitive deficit, whereas memory disorders (typical of the elderly patient's AD) are less often in the foreground. In addition, some MA-J have an atypical phenotype indicating focal brain damage, although they have the same pathological lesions: amyloid deposits and tau protein deposition (DNF). This is the case of posterior cortical atrophy (PCA) characterized by complex visual disturbances and atrophy affecting the more posterior regions of the brain. Based on the clinical profile of PCA patients, a more refined anatomo-clinical classification was proposed, distinguishing a rather "ventral" form and a rather "dorsal" form. The recent arrival of tau-specific PET tracers now makes it possible to evaluate in vivo fibrillary neurodegeneration (FND), which is well correlated with the severity of cognitive disorders. Advances in MRI have shown that each neurodegenerative syndrome targets a large-scale neural network, which in turn shows a vulnerability for a specific biological disease. In the case of AD, the reason for such a difference in cognitive and anatomical impairment between patients with diffuse involvement and others with more focal involvement is not known. One possible explanation is the existence, in focal forms, of neuronal mechanisms that oppose vulnerability. These mechanisms may correspond to the so-called "resilience" phenomenon, defined as resistance to a neuropathological process by the ability to optimize cognitive performance via the efficient recruitment of neural networks. The mechanisms underlying resilience in neurodegeneration are unknown. Their identification is very important for the management and treatment of AD.
Detailed description
Working hypotheses We hypothesize that "focal" patients (PCA) versus "diffuse" patients (AD-Y) have (i) less severe white matter involvement; (ii) effective reorganization of the functional brain networks; iii) pathologically, a different topography and lesion load.
This project has no redundancy with the work already done in our team and in other teams at the international level.
Expected benefits This study will highlight the neural mechanisms underlying resiliency in a group of AD patients who, although having the same disease, present with a very different clinical and cognitive profile. Demonstration of these specific mechanisms of resilience in the diseased brain is essential to better understand the pathophysiological processes of AD. We consider that the pharmacological approach and the functional reeducation to this disease depend essentially on a better knowledge of both the topographic distribution of the underlying histopathology (in particular, the tau protein), and the response capacity from the brain to these lesions (state of connection of networks, functional reorganization). In addition, when treatments for AD are available, a precise definition of phenotypic variants will be essential for the selection of patients for these therapies and for therapeutic follow-up. In the longer term, resilient neural circuits could be modulated and strengthened through transcranial stimulation. Indeed, promising results have been obtained showing that these techniques can improve the performance of altered cognitive functions in patients with dementia.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Nombre de participants 45 sujets répartis dans 3 groupes: 1. Groupe MA-J (Maladie d'Alzheimer précoce)= 15 patients avec un diagnostic de MA-J 2. Groupe ACP (Atrophie Corticale Posterieure)= 15 patients avec un diagnostic d'ACP 3. Groupe sujets contrôles= 15 sujets contrôles
| Arm | Type | Receives |
|---|---|---|
| Patients with Alzheimer (<65 years) (AD-Y) | Experimental | Device: TEP/IRM15 patients with a diagnostic of MA-J |
| Patients with posterior Cortical Atrophy (PCA) | Experimental | Device: TEP/IRM15 patients with a diagnostic of PCA |
| Control | Active comparator | Device: TEP/IRM15 controls |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (45 listed)
- For all subjects:
- Selection of AD-Y group
- In memory tests, the amnesic hippocampal syndrome is defined by: a deficit of the free recall despite a reinforced encoding, an effectiveness of the indexing or an impairment of the recognition capabilities, the presence of intrusions. The presence during the tests of false memories spontaneous (intrusions) or provoked (false recognitions) is also very contributive to the definition of amnesic syndrome of the hippocampal type.
- PCA group selection
- Selection of the control subjects group
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| TEP/IRMAll participants will have a PET / MRI examination including: i) a 30-minute PET scan, 80 minutes after intravenous injection of 240 MBq of 18F-AV1451 ± 10% ii) a ZTE sequence (for attenuation correction of PET images), a 3D T1 anatomical sequence, a diffusion MRI, a functional MRI at rest (total duration: 45 minutes). These acquisitions will be made during the same exam session on a hybrid PET / MRI camera allowing simultaneous acquisitions. This visit lasts about 3 hours. | Device | Control, Patients with Alzheimer (<65 years) (AD-Y), Patients with posterior Cortical Atrophy (PCA) |
Primary outcome
highlight of the "resilient" neural networks
Time frame: up to 3 months
For this, we will study: 1) The topographic distribution regions of tau lesions, thanks to PET brain imaging using the 18F-AV-1451 as a ligand.
quantify the impairment (ie brain vulnerability) in AD-Y and in PCA
Time frame: up to 3 months
For this, we will study: 2) The correlation between the distribution of these tau lesions and: the cortical volume, the indices of integrity of the white matter bundles, the functional neural networks, as well as the reorganization of the "hubs" of these networks, thanks to the structural MRI, diffusion (MRI) and functional at rest (fMRI) imaging.2)
2 secondary outcomes
correlation between the concentration of tau-tauphosphorylated protein in cerebrospinal fluid (CSF) with the lesion load measured in PET
Time frame: up to 3 months
predictive model of functional alterations based on the structural alterations of the gray matter and the white matter.
Time frame: up to 3 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 20 Aug 2026.
- Individual participant dataSharing planned: Undecided
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TEP/IRM in people with Alzheimer Disease, Early Onset and Posterior Cortical Atrophy, run by Institut National de la Santé Et de la Recherche Médicale, France at 2 sites 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 45 inclusion and 0 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 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Marie Odile Habert, MCU-PH (01 57 27 40 00, marie-odile.habert@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
highlight of the "resilient" neural networks (time frame: up to 3 months). 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 20 Aug 2026.