Alzheimer DiseaseGliSynNCT05911178
Impact of Microglial Activation on Synaptic Density in Alzheimer's Disease
A study testing [11C]-UCB-J, [18F]-DPA-714 and [18F]-RO-948 in people with Alzheimer Disease, run by Centre Hospitalier St Anne at 3 sites in France.
Trial summary
This study aims to analyse, in vivo, the interplay between microglial activation and tau pathology in Alzheimer's disease (AD) using [18F]-DPA-714 and [18F]-Ro948 tracers by Position Emission Tomography (PET), and their consequences on synaptic density using [11C]-UCB-J, a recent PET radioligand. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- [11C]-UCB-J, [18F]-DPA-714 and [18F]-RO-948
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 3 sitesFrance
- Study dates
- 18 Oct 2023to 17 Oct 2028
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General Inclusion Criteria:
- Adult (older than 18 years)
- Women old enough to procreate under effective contraception
- Signed consent
- Absence of general or systemic disorders that may interfere with cognition.
- Progressive amnestic syndrome, associated or not with other cognitive impairments,
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- CDR = 0.5 or 1
- Absence of general or systemic disorders that may interfere with cognition or PET imaging analysis,
- Absence of brain lesions as determined by MRI carried out within the framework of usual care.
- Presence of CSF biomarkers profile suggestive of AD
- absence of subjective problems with memory and normal scores on the MMSE (MMSE > 27) with no more than one word missing.
- older than 50 years old.
- Scores on the Free and Cued Selective Reminding Test (FCSRT) of >25 for free recall and >44 for total recall.
- absence of general or systemic disorders that may interfere with cognition at follow-up.
- Controls will be matched to AD patients for age and education level.
Who cannot join
- Subject with a psychiatric evolutionary and/or poorly checked pathology (left to the judgement of the investigator).
- Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
- Current auto-immune disease
- Subject presenting contraindications to the 3T MRI
- Known or supposed histories (≤5 years) of severe alcoholism or misuse of drugs
- Vascular, inflammatory or expansive, visible lesion in the MRI which can interfere on the criteria of diagnosis.
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- No health insurance
- Pregnant, breast-feeding woman or planning a pregnancy in two years of follow-up.
- Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders.
- Person placed under the protection of justice
- Patient under guardianship or curatorship
Trial locations and contacts
3 sites in 1 country.
France3 sites
CHU de Lille
Lille
GHU Saint Anne Psychiatrie & Neurosciences
Paris
CHU de Rouen
Rouen
About this study
This study aims to analyse, in vivo, the interplay between microglial activation and tau pathology in Alzheimer's disease (AD) using [18F]-DPA-714 and [18F]-Ro948 tracers by Position Emission Tomography (PET), and their consequences on synaptic density using [11C]-UCB-J, a recent PET radioligand.
By coupling advanced neuroimaging techniques in AD patients, while comparing them to controls, we will be able to study, for the first time in humans, the interaction between neuroinflammation, tau pathology, synaptic density, and their impact on AD progression. Joint analyses of peripheral immune biomarkers, carried out as a secondary objective, will further aim at defining peripheral correlates of this interplay.
Overall, we aim to refine AD subgroup classification in order to improve and to refine the design of new therapeutic trials.
Read the detailed description
The present study aims to reevaluate the interplay between microglial activation, tau pathology, and synaptic density. It is an interventional, comparative, controlled, non-randomized study in which AD patients will be matched to controls. In order to better our current understanding of pathophysiological processes of neuroinflammation in AD, we will analyze regional microglial activation, cortical tau deposition, and synaptic dysfunction by employing multiple PET radioligands and MRI. The hybrid images will be acquired at baseline and at two years.
This study design opens the door to a multimodal study; first transversal (by determining whether the level and the extent of DPA-714 binding are associated with synaptic loss and tau deposition) then longitudinal (after a two-year follow-up based on PET/MRI, cognitive and clinical assessment and peripheral immune biomarkers). By using PET imaging at baseline and at two years, we will investigate the neuroinflammation dynamics in sporadic AD and its consequences on neurodegenerative biomarkers as well as its clinical repercussions.
Conservative diagnosis criteria based on clinical and CSF biomarkers have been established to avoid risks of misdiagnosis for the patients. The controls will undergo, at inclusion, an additional PiB-PET imaging to avoid bias and to identify amyloid positive controls.
A complete clinical and cognitive evaluation will accompany the image acquisition at baseline. The subjects will be followed up clinically at one year. At two years, another set of PET/MRIs will be performed as well as a cognitive evaluation. The image acquisitions will be planned within 6 months of each clinical visit at baseline and at two years.
- Conditions
- Alzheimer Disease
- Being tested
- [11C]-UCB-J, [18F]-DPA-714, [18F]-RO-948, [11C]-PiB
- Keywords
- Neuroinflammation, Microglial activation, Synaptic density, Tau pathology, Peripheral immunity
- Medical subject headings
- Alzheimer Disease, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]-UCB-JRadiation
PET tracer binding to "SV2A" protein, used to study synaptic vesicle density.
[18F]-DPA-714Radiation
PET tracer binding to "TSPO" protein, used to study microglial activation.
[18F]-RO-948Radiation
PET tracer binding to "tau" protein, used to study the topography of tau deposition.
[11C]-PiBRadiation
PET tracer binding to Aβ40 and Aβ42 fibrils and insoluble plaques containing the aforementioned Aß peptides, used to study the topography of amyloid deposition.
| Study group | Role | What they receive |
|---|---|---|
| Early Onset Alzheimer's Disease (EOAD) | Experimental | Patients who have been diagnosed with AD according to clinical and biomarker criteria. Early onset AD is considered as having an age of onset of symptoms younger than 65 years.
Age of onset ≤ 65 years Receives: Radiation: [11C]-UCB-J; Radiation: [18F]-DPA-714; Radiation: [18F]-RO-948 |
| Late Onset Alzheimer's Disease (LOAD) | Experimental | Patients who have been diagnosed with AD according to clinical and biomarker criteria. Late onset AD is considered as having an age of onset of symptoms older than 65 years.
Age of onset > 65 years Receives: Radiation: [11C]-UCB-J; Radiation: [18F]-DPA-714; Radiation: [18F]-RO-948 |
| Controls | Experimental | Healthy control subjects will be matched to patients for age and education level. Receives: Radiation: [11C]-UCB-J; Radiation: [18F]-DPA-714; Radiation: [18F]-RO-948; Radiation: [11C]-PiB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in regional microglial activation and tau pathology from baseline at 24 months
The first primary endpoint will be evaluated and compared to baseline across all participants (patients and controls). The microglial activation and tau pathology will be measured respectively with [18F]-DPA-714 and [18F]-RO-948 binding rate at baseline and again at 24 months. The change will be calculated by comparing the baseline and 24-month uptake ratios.
Measured: 24 months
Change in regional synaptic density from baseline at 24 months
The second primary endpoint will be evaluated and compared to baseline across all participants (patients and controls). The synaptic density will be measured with [11C]-UCB-J. We hypothesize that both tau pathology and microglial activation will modulate regional synaptic density, which is responsible for clinical symptoms. The change will be calculated by comparing the baseline and 24-month uptake ratios.
Measured: 24 months
Secondary outcomes (7)
Change in neuroimmune reaction as assessed by [18F]-DPA-714 PET global cortical index and regional cortical binding at baseline and at 24 months across all participants
Global and regional cortical [18F]-DPA-714 uptake ratio.
Measured: 24 months
Incidence of novel peripheral and CSF immune biomarkers across all participants at baseline, at 1 year, and at 2 years
Peripheral and CSF immune biomarkers will be identified by broad spectrum immunophenotyping in order to determine, if any, novel biological markers of prognosis on disease evolution over 1 and 2 years of follow-up.
Measured: 24 months
Rate of clinical disease progression as impacted by global and regional tau deposition at baseline, at 1 years, and at 2 years
Clinical presentation of symptoms will be mainly evaluated by the changes in MMSE (total score out of 30) and CDR (total score out of 3) scores. And it will be compared with the topography of tau deposition (measured by [18F]-RO-948) for each patient.
Measured: 24 months
Rate of clinical disease progression as impacted by global and regional synaptic density at baseline, at 1 years, and at 2 years
Clinical presentation of symptoms will be mainly evaluated by the changes in MMSE (total score out of 30) and CDR (total score out of 3) scores. And it will be compared with the synaptic density (measured by [11C]-UCB-J) for each patient.
Measured: 24 months
Comparison of the rate of central and systemic inflammation between sporadic AD groups assessed by [18F]-DPA-714 PET global cortical index and regional cortical binding at baseline and at 24 months
Global and regional cortical [18F]-DPA-714 uptake ratio across the patient groups.
Measured: 24 months
Correlation of the rate of clinical decline with the rate of PET tracer uptake increase at 24 months across all patients.
Global and regional uptake ratios will be compared to the rate of clinical decline as assessed by changes in MMSE (x/30) and CDR (x/3) scores
Measured: 24 months
Correlation between the rate of clinical decline and the rate of regional atrophy as assessed by MRI scans at baseline and at 24 months across all participants
Clinical decline is assessed by the changes in MMSE (x/30) and CDR (x/3) scores. MRI scans are performed simultaneously during hybrid PET-MRI scans.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2023
- Study start18 Oct 2023
- Primary completion17 Oct 2028 (estimated)
- Study completion17 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier St AnneThe 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
- Screening
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Early and late onset AD subjects, matched to controls for age and education level, will be followed up for two years, allowing both longitudinal and cross-sectional comparisons.
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier St Anne
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Marie SARAZIN, MD, Prof, Principal investigator, GHU Sainte-AnneGuillaume DOROTHEE, PhD, Study chair, INSERM UMRS 938Michel BOTTLAENDER, PhD, Study chair, Service Hospitalier Frédéric Jolit / CEAMarie Claude POTIER, PhD, Study chair, Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05911178
- Sponsor's protocol ID
- D23-P006
- Acronym
- GliSyn
- Status last verified
- Jul 2026
- First submitted
- 12 Jun 2023
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Microglial Activation on Synaptic Density in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05911178
- Acronym / sponsor ID
- GliSyn / D23-P006
- Conditions
- Alzheimer Disease
- Keywords
- Neuroinflammation, Microglial activation, Synaptic density, Tau pathology, Peripheral immunity
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Centre Hospitalier St AnneUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- 18 Oct 2023 (actual)
- Primary completion
- 17 Oct 2028 (estimated)
- Study completion
- 17 Oct 2028 (estimated)
- First posted
- 20 Jun 2023 (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.
This study aims to analyse, in vivo, the interplay between microglial activation and tau pathology in Alzheimer's disease (AD) using [18F]-DPA-714 and [18F]-Ro948 tracers by Position Emission Tomography (PET), and their consequences on synaptic density using [11C]-UCB-J, a recent PET radioligand.
By coupling advanced neuroimaging techniques in AD patients, while comparing them to controls, we will be able to study, for the first time in humans, the interaction between neuroinflammation, tau pathology, synaptic density, and their impact on AD progression. Joint analyses of peripheral immune biomarkers, carried out as a secondary objective, will further aim at defining peripheral correlates of this interplay.
Overall, we aim to refine AD subgroup classification in order to improve and to refine the design of new therapeutic trials.
Detailed description
The present study aims to reevaluate the interplay between microglial activation, tau pathology, and synaptic density. It is an interventional, comparative, controlled, non-randomized study in which AD patients will be matched to controls. In order to better our current understanding of pathophysiological processes of neuroinflammation in AD, we will analyze regional microglial activation, cortical tau deposition, and synaptic dysfunction by employing multiple PET radioligands and MRI. The hybrid images will be acquired at baseline and at two years.
This study design opens the door to a multimodal study; first transversal (by determining whether the level and the extent of DPA-714 binding are associated with synaptic loss and tau deposition) then longitudinal (after a two-year follow-up based on PET/MRI, cognitive and clinical assessment and peripheral immune biomarkers). By using PET imaging at baseline and at two years, we will investigate the neuroinflammation dynamics in sporadic AD and its consequences on neurodegenerative biomarkers as well as its clinical repercussions.
Conservative diagnosis criteria based on clinical and CSF biomarkers have been established to avoid risks of misdiagnosis for the patients. The controls will undergo, at inclusion, an additional PiB-PET imaging to avoid bias and to identify amyloid positive controls.
A complete clinical and cognitive evaluation will accompany the image acquisition at baseline. The subjects will be followed up clinically at one year. At two years, another set of PET/MRIs will be performed as well as a cognitive evaluation. The image acquisitions will be planned within 6 months of each clinical visit at baseline and at two years.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Early and late onset AD subjects, matched to controls for age and education level, will be followed up for two years, allowing both longitudinal and cross-sectional comparisons.
| Arm | Type | Receives |
|---|---|---|
| Early Onset Alzheimer's Disease (EOAD) | Experimental | Radiation: [11C]-UCB-J, Radiation: [18F]-DPA-714, Radiation: [18F]-RO-948Patients who have been diagnosed with AD according to clinical and biomarker criteria. Early onset AD is considered as having an age of onset of symptoms younger than 65 years. Age of onset ≤ 65 years |
| Late Onset Alzheimer's Disease (LOAD) | Experimental | Radiation: [11C]-UCB-J, Radiation: [18F]-DPA-714, Radiation: [18F]-RO-948Patients who have been diagnosed with AD according to clinical and biomarker criteria. Late onset AD is considered as having an age of onset of symptoms older than 65 years. Age of onset > 65 years |
| Controls | Experimental | Radiation: [11C]-UCB-J, Radiation: [18F]-DPA-714, Radiation: [18F]-RO-948, Radiation: [11C]-PiBHealthy control subjects will be matched to patients for age and education level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Adult (older than 18 years)
- Women old enough to procreate under effective contraception
- Signed consent
- Absence of general or systemic disorders that may interfere with cognition.
- Progressive amnestic syndrome, associated or not with other cognitive impairments,
Key exclusion criteria (11 listed)
- Subject with a psychiatric evolutionary and/or poorly checked pathology (left to the judgement of the investigator).
- Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
- Current auto-immune disease
- Subject presenting contraindications to the 3T MRI
- Known or supposed histories (≤5 years) of severe alcoholism or misuse of drugs
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 |
|---|---|---|
| [11C]-UCB-JPET tracer binding to "SV2A" protein, used to study synaptic vesicle density. | Radiation | Controls, Early Onset Alzheimer's Disease (EOAD), Late Onset Alzheimer's Disease (LOAD) |
| [18F]-DPA-714PET tracer binding to "TSPO" protein, used to study microglial activation. | Radiation | Controls, Early Onset Alzheimer's Disease (EOAD), Late Onset Alzheimer's Disease (LOAD) |
| [18F]-RO-948PET tracer binding to "tau" protein, used to study the topography of tau deposition. | Radiation | Controls, Early Onset Alzheimer's Disease (EOAD), Late Onset Alzheimer's Disease (LOAD) |
| [11C]-PiBPET tracer binding to Aβ40 and Aβ42 fibrils and insoluble plaques containing the aforementioned Aß peptides, used to study the topography of amyloid deposition. | Radiation | Controls |
Primary outcome
Change in regional microglial activation and tau pathology from baseline at 24 months
Time frame: 24 months
The first primary endpoint will be evaluated and compared to baseline across all participants (patients and controls). The microglial activation and tau pathology will be measured respectively with [18F]-DPA-714 and [18F]-RO-948 binding rate at baseline and again at 24 months. The change will be calculated by comparing the baseline and 24-month uptake ratios.
Change in regional synaptic density from baseline at 24 months
Time frame: 24 months
The second primary endpoint will be evaluated and compared to baseline across all participants (patients and controls). The synaptic density will be measured with [11C]-UCB-J. We hypothesize that both tau pathology and microglial activation will modulate regional synaptic density, which is responsible for clinical symptoms. The change will be calculated by comparing the baseline and 24-month uptake ratios.
7 secondary outcomes
Change in neuroimmune reaction as assessed by [18F]-DPA-714 PET global cortical index and regional cortical binding at baseline and at 24 months across all participants
Time frame: 24 months
Incidence of novel peripheral and CSF immune biomarkers across all participants at baseline, at 1 year, and at 2 years
Time frame: 24 months
Rate of clinical disease progression as impacted by global and regional tau deposition at baseline, at 1 years, and at 2 years
Time frame: 24 months
Rate of clinical disease progression as impacted by global and regional synaptic density at baseline, at 1 years, and at 2 years
Time frame: 24 months
Comparison of the rate of central and systemic inflammation between sporadic AD groups assessed by [18F]-DPA-714 PET global cortical index and regional cortical binding at baseline and at 24 months
Time frame: 24 months
Correlation of the rate of clinical decline with the rate of PET tracer uptake increase at 24 months across all patients.
Time frame: 24 months
Correlation between the rate of clinical decline and the rate of regional atrophy as assessed by MRI scans at baseline and at 24 months across all participants
Time frame: 24 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 22 Jul 2026.
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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. This study is not recruiting at the moment.
Marie SARAZIN, MD, Prof principal investigator
GHU Sainte-Anne
Guillaume DOROTHEE, PhD study chair
INSERM UMRS 938
Michel BOTTLAENDER, PhD study chair
Service Hospitalier Frédéric Jolit / CEA
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [11C]-UCB-J, [18F]-DPA-714 and [18F]-RO-948 in people with Alzheimer Disease, run by Centre Hospitalier St Anne at 3 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 15 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in regional microglial activation and tau pathology from baseline at 24 months (time frame: 24 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 22 Jul 2026.