Alzheimer DiseasePhase 2NCT04840979
Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease
A Phase 2 study testing 11C-ER176 and 18F-florbetaben in people with Alzheimer Disease, run by Columbia University at 1 site in United States.
Trial summary
The primary objectives are to validate that a previously identified gene variant influences the proportion of activated microglia (PAM) and the amount of TSPO binding on PET imaging, to identify novel loci that influence PAM and TSPO PET, and to understand the functional consequences of gene variants that drive… Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- 11C-ER176 and 18F-florbetaben
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2021to Dec 2026
- Phase
- Phase 2
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 50 and older at time of study entry.
- Meet criteria for either a) amnestic mild cognitive impairment (single or mixed domain) or Alzheimer's disease, or b) have no cognitive impairment, based on history, exam, and neuropsychological testing.
- Patients must have Clinical Dementia Rating Scale score of 0.5 or 1 at enrollment. Controls must have Clinical Dementia Rating scale score of 0 at enrollment.
- Subjects must have AD biomarker previously obtained for research or clinical purposes or undergo a 18F-florbetaben PET scan during the screening process. Patients must have positive amyloid PET scan or CSF results consistent with AD. Controls must have a negative amyloid PET scan or CSF results not consistent with AD.
- Self-identify as white, non-Hispanic or Latino
- Subjects must be ableto provide informed consent
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- Written and oral fluency in English
- Able to participate in all scheduled evaluations and to complete all required tests and procedures.
- In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.
Who cannot join
- Past or present history of certain brain disorders other than MCI or AD.
- Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries.
- Contraindication to MRI scanning
- Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.).
- Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
- Participation in the last year in a clinical trial for a disease modifying drug for AD.
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- Inability to have a catheter in subject's vein for the injection of radioligand.
- Inability to have blood drawn from subject's veins.
- Taking anticoagulant (e.g., warfarin) or immunosuppressive/immunomodulatory medication. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not exclusionary. Use of steroids in the 30 days preceding the PET scan.
- Having a diagnosis of a chronic inflammatory disease (for example, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus) or a chronic infectious disease such as H.I.V.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease With 11C-ER176
The primary objectives are to validate that a previously identified gene variant influences the proportion of activated microglia (PAM) and the amount of TSPO binding on PET imaging, to identify novel loci that influence PAM and TSPO PET, and to understand the functional consequences of gene variants that drive microglial activation in Alzheimer's disease.
Read the detailed description
While activated microglia have been observed in the vicinity of neuritic amyloid plaques in Alzheimer's disease (AD), there have been no large-scale assessments of microglial activation in aging and neurodegenerative disease. The investigators seek to understand the genetic underpinning of microglial responses-particularly the proportion of microglia in a morphologically-defined state of activation-that increase susceptibility to AD, so the investigators can develop more targeted forms of immune-based therapies to prevent cognitive decline and progression to dementia. The objective is to refine the genetic architecture of microglial activation to validate a previously identified gene variant -- and to identify novel loci -- that influence the proportion of activated microglia. The investigators also seek to understand the functional consequences of variants driving microglial activation in AD.
The central hypothesis is that identifiable gene variants influence microglial activation and susceptibility to AD. The investigators will test this hypothesis by conducting genome-wide analysis and identifying associations between gene variants and microglial activation. Microglial activation will be measured in human autopsy tissue (ex vivo), living human brain using PET imaging (in vivo), and in monocyte-derived microglia-like cells (in situ and in vitro).
This genetic study is designed to validate a finding that was discovered in participants with self-reported European-Caucasian ancestry. Therefore, the study seeks to enroll participants who self-report as white, not Hispanic or Latino. However, if this study is successful, the investigators plan to use the methods in this protocol in a future study to identify new genetic variants associated with changes on TSPO PET in a more diverse participant population. The investigators intend to use the results from this study to eventually benefit individuals of all racial and ethnic groups.
- Conditions
- Alzheimer Disease
- Being tested
- 11C-ER176, 18F-florbetaben
- Keywords
- PET scan, Inflammation, Genetic testing, Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Inflammation, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-ER176Drug
Also called [11C]ER176
11C-ER176 is a novel TSPO radioligand that was developed because of its relative insensitivity to the rs6971 polymorphism. Increased TSPO signal on PET is associated with activation of microglia in the brain. The radioligand will be administered in tracer doses at activity of up to 20 mCi (740 MBq), IV, total of one injection. A single dose of radioligand will be injected over 1 minute.
18F-florbetabenDrug
Also called [18F] Florbetaben
Florbetaben has been approved by the FDA to help diagnose Alzheimer's disease. Florbetaben measures amyloid in the brain.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Impairment | Experimental | Subjects diagnosed with Alzheimer's disease (AD) or mild cognitive impairment (MCI) will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo a 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses. Receives: Drug: 11C-ER176; Drug: 18F-florbetaben |
| No Cognitive Impairment | Active comparator | Healthy volunteers who are cognitively normal will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo an 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses. Receives: Drug: 11C-ER176; Drug: 18F-florbetaben |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between the chromosome 1 variant (rs2997325) and TSPO binding
The measure will be in vivo validation of GWAS and assessment of clinical relevance by performing TSPO PET imaging using 11C-ER176 to measure microglial activation. PET images will be analyzed using 1) the two-tissue kinetic model to calculate total distribution volume, corrected for free fraction of radioligand in plasma (VT/fP). Analysis will be a meta-analysis of the association of rs2997325 with 11C-ER176 binding (total distribution volume, VT).
Measured: Up to 1 year
Number of variants discovered in genome-wide association study (GWAS) that influence TSPO binding
11C-ER176 data will be used to perform a discovery GWAS for additional variants that influence TSPO binding and to define the genetic architecture of the PAM trait. Using PLINK and all imputed high quality genotypes (imputation r2 >0.8), adjusted for sex, age, and technical variables, the investigators will perform a GWAS for TSPO binding.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start11 May 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (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 Columbia UniversityThe 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 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Philip De Jager, Columbia University
- Investigators
- Philip De Jager, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04840979
- Sponsor's protocol ID
- AAAT2774
- Other IDs
- RF1AG070438
- Status last verified
- May 2026
- First submitted
- 8 Apr 2021
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will be available upon reasonable request from a qualified investigator.
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease With 11C-ER176
- ClinicalTrials.gov ID
- NCT04840979
- Acronym / sponsor ID
- AAAT2774
- Conditions
- Alzheimer Disease
- Keywords
- PET scan, Inflammation, Genetic testing, Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 11 May 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Apr 2021 (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.
The primary objectives are to validate that a previously identified gene variant influences the proportion of activated microglia (PAM) and the amount of TSPO binding on PET imaging, to identify novel loci that influence PAM and TSPO PET, and to understand the functional consequences of gene variants that drive microglial activation in Alzheimer's disease.
Detailed description
While activated microglia have been observed in the vicinity of neuritic amyloid plaques in Alzheimer's disease (AD), there have been no large-scale assessments of microglial activation in aging and neurodegenerative disease. The investigators seek to understand the genetic underpinning of microglial responses-particularly the proportion of microglia in a morphologically-defined state of activation-that increase susceptibility to AD, so the investigators can develop more targeted forms of immune-based therapies to prevent cognitive decline and progression to dementia. The objective is to refine the genetic architecture of microglial activation to validate a previously identified gene variant -- and to identify novel loci -- that influence the proportion of activated microglia. The investigators also seek to understand the functional consequences of variants driving microglial activation in AD.
The central hypothesis is that identifiable gene variants influence microglial activation and susceptibility to AD. The investigators will test this hypothesis by conducting genome-wide analysis and identifying associations between gene variants and microglial activation. Microglial activation will be measured in human autopsy tissue (ex vivo), living human brain using PET imaging (in vivo), and in monocyte-derived microglia-like cells (in situ and in vitro).
This genetic study is designed to validate a finding that was discovered in participants with self-reported European-Caucasian ancestry. Therefore, the study seeks to enroll participants who self-report as white, not Hispanic or Latino. However, if this study is successful, the investigators plan to use the methods in this protocol in a future study to identify new genetic variants associated with changes on TSPO PET in a more diverse participant population. The investigators intend to use the results from this study to eventually benefit individuals of all racial and ethnic groups.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cognitive Impairment | Experimental | Drug: 11C-ER176, Drug: 18F-florbetabenSubjects diagnosed with Alzheimer's disease (AD) or mild cognitive impairment (MCI) will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo a 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses. |
| No Cognitive Impairment | Active comparator | Drug: 11C-ER176, Drug: 18F-florbetabenHealthy volunteers who are cognitively normal will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo an 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 50 and older at time of study entry.
- Meet criteria for either a) amnestic mild cognitive impairment (single or mixed domain) or Alzheimer's disease, or b) have no cognitive impairment, based on history, exam, and neuropsychological testing.
- Patients must have Clinical Dementia Rating Scale score of 0.5 or 1 at enrollment. Controls must have Clinical Dementia Rating scale score of 0 at enrollment.
- Subjects must have AD biomarker previously obtained for research or clinical purposes or undergo a 18F-florbetaben PET scan during the screening process. Patients must have positive amyloid PET scan or CSF results consistent with AD. Controls must have a negative amyloid PET scan or CSF results not consistent with AD.
- Self-identify as white, non-Hispanic or Latino
Key exclusion criteria (10 listed)
- Past or present history of certain brain disorders other than MCI or AD.
- Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries.
- Contraindication to MRI scanning
- Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.).
- Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
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-ER176Also: [11C]ER17611C-ER176 is a novel TSPO radioligand that was developed because of its relative insensitivity to the rs6971 polymorphism. Increased TSPO signal on PET is associated with activation of microglia in the brain. The radioligand will be administered in tracer doses at activity of up to 20 mCi (740 MBq), IV, total of one injection. A single dose of radioligand will be injected over 1 minute. | Drug | Cognitive Impairment, No Cognitive Impairment |
| 18F-florbetabenAlso: [18F] FlorbetabenFlorbetaben has been approved by the FDA to help diagnose Alzheimer's disease. Florbetaben measures amyloid in the brain. | Drug | Cognitive Impairment, No Cognitive Impairment |
Primary outcome
Correlation between the chromosome 1 variant (rs2997325) and TSPO binding
Time frame: Up to 1 year
The measure will be in vivo validation of GWAS and assessment of clinical relevance by performing TSPO PET imaging using 11C-ER176 to measure microglial activation. PET images will be analyzed using 1) the two-tissue kinetic model to calculate total distribution volume, corrected for free fraction of radioligand in plasma (VT/fP). Analysis will be a meta-analysis of the association of rs2997325 with 11C-ER176 binding (total distribution volume, VT).
Number of variants discovered in genome-wide association study (GWAS) that influence TSPO binding
Time frame: Up to 1 year
11C-ER176 data will be used to perform a discovery GWAS for additional variants that influence TSPO binding and to define the genetic architecture of the PAM trait. Using PLINK and all imputed high quality genotypes (imputation r2 >0.8), adjusted for sex, age, and technical variables, the investigators will perform a GWAS for TSPO binding.
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 14 May 2026.
- Individual participant dataSharing planned: Yes. Individual participant data will be available upon reasonable request from a qualified investigator.
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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.
Philip De Jager, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 11C-ER176 and 18F-florbetaben in people with Alzheimer Disease, run by Columbia University at 1 site in United States.
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 10 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 14 May 2026. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Correlation between the chromosome 1 variant (rs2997325) and TSPO binding (time frame: Up to 1 year). 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 14 May 2026.