Alzheimer DiseasePhase 2NCT04871074
The Synapse Project
A Phase 2 study testing UCB-J, MRI Scan and PET Scan in people with Alzheimer Disease, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The overarching goal of this project is to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform Alzheimer's disease (AD) progression. The investigators propose to collect longitudinal amyloid, tau, and Synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) in… Read more about this study
- Who is it for?
- Ages 55 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- UCB-J, MRI Scan and PET Scan
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Nov 2018to 1 May 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Cognitively unimpaired adults-
- Aged 55 - 89
- Normal cognition (results of most recent testing with the source cohort indicate the participant is cognitively unimpaired as judged by consensus or expert review)
- In good general health with no conditions/medications affecting cognition or imaging
- Willing to undergo [C-11]UCB-J, [C-11]PiB, and [F-18]MK6240 PET scans
- An adequate MRI exam within 12 months prior to baseline. An MRI will be performed if not already available.
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- Mild dementia and amnestic Mild Cognitive Impairment-
- Aged 50 years or older
- Abnormal cognitive status of MCI or dementia as judged by consensus or expert review using NIA-AA 2018 criteria
- MCI's must be affected in the memory domain but may also have other affected domains
- Willing to undergo [C-11]UCB-J, [C-11]PiB, and [F-18]MK6240 PET scans
- An adequate MRI exam within 12 months prior to baseline. This MRI exam will come from ADRC/WRAP studies. Clinical MRI's (ones obtained outside of the research program) will not be adequate. An MRI will be performed if not already available from within the research program.
Who cannot join
- For women, pregnant, lactating or breastfeeding, or intention to become pregnant
- Evidence of unstable or untreated clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Stable, treated chronic medical conditions like hypertension, hypercholesterolemia, diabetes mellitus, non-metastatic dermatologic or prostatic cancer, etc. are acceptable as long as they do not, in the study investigator's opinion, contribute to cognitive dysfunction or limit participation in study procedures.
- Any illness or other consideration that makes it unlikely that the subject will be able to complete the 24-month study.
- Current or prior history (within past 5 years) of significant alcohol or substance abuse as determined by the investigator.
- Psychiatric disorders that may interfere with the study including current major Axis I DSM-V disorders including but not limited to severe Major depression, current or history of bipolar I disorder, or schizophrenia.
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- Current use of the anti-seizure medication Levetiracetam, also known as Keppra, Spritam or Roweepra
- MRI exclusion criteria include findings from previous MRI's within the ADRC/WRAP research program that may be responsible for neurologic status of the subject such as evidence of cerebrovascular disease with multiple infarcts, infectious disease, space-occupying lesion, normal pressure hydrocephalus, CNS trauma, or any other structural abnormality that may impact cognition or image analysis, as judged by the investigator.
- MRI-incompatible implants or devices such as certain cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI that prevents completion of MRI protocol.
- Lack of decisional capacity at the time of informed consent
- Lumbar puncture exclusion criteria include: previous lumbar spine surgery, currently taking blood-thinning anti-platelet medications, taking immunosuppressive medications, currently being treated or were recently treated for an infection or virus within the last 2 to 3 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: SV2A PET Imaging in Alzheimer's Disease
The overarching goal of this project is to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform Alzheimer's disease (AD) progression. The investigators propose to collect longitudinal amyloid, tau, and Synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) in participants in the Wisconsin Alzheimer's Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer's Prevention (WRAP) across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, mild cognitive impairment (MCI), and dementia due to AD.
Read the detailed description
Synaptic loss is a major feature of symptomatic AD. Conversely, abundance of synapses may confer resilience to cognitive decline in the presence of AD pathology. The pathology-defining features of AD are amyloid plaques and neurofibrillary tangles and their presence and distribution can be spatially estimated in-vivo with amyloid and tau PET. Although these biomarkers can inform on the degree and location of pathology, they do not provide an indicator of their effect on collocated or extended in-network neural damage including synaptic density.
SV2A is expressed ubiquitously in synapses and the capability of assessing SV2A in vivo may provide a direct indicator of synaptic health. Such information would be of high importance for staging the level of synaptic loss or conversely synaptic abundance in the AD continuum and may potentially improve prognostic precision. The PET radioligand [C-11]UCB-J is a marker of SV2A.
The overarching goal of this project is to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform upon disease progression. The investigators propose to collect longitudinal amyloid, tau, and SV2A PET in participants in the Wisconsin ADRC and WRAP across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, MCI, and dementia due to AD.
- Specific Aim 1). Determine the extent to which [C-11]UCB-J provides unique information from MRI regarding neurodegeneration. Approach: The investigators will recruit N=60 cognitively unimpaired participants, N=30 MCI participants, and N=30 participants with AD dementia to undergo PET imaging with [C-11]UCB-J. MRI will include anatomic and diffusion connectivity MRI. When available, ancillary cerebrospinal fluid (CSF) indicators of neurodegeneration and synapse function will be examined for relationships with UCB-J.
- Specific Aim 2). Determine the rate of synapse loss as reflected by [C-11]UCB-J signal across all participants. Rationale: Trajectories of synaptic loss are unknown in vivo. Approach: The investigators will determine the longitudinal trajectories of regional synapse loss that are observed over time among participants who undergo repeat [C-11]UCB-J (separated by two years, same participants scanned for Aim 1). The investigators will also examine trajectories by amyloid and tau load. Quantifying longitudinal synaptic loss is expected to eventually facilitate the identification of individuals who are progressing to dementia, as well as inform upon changes that are normal for age.
- Specific Aim 3). Determine the extent to which [C-11]UCB-J associates with cognitive decline. Rationale: The investigators expect that lower baseline SV2A density and longitudinal decline in SV2A density in the medial temporal lobe will be associated with faster progression of cognitive decline. The investigators will also test the extent to which harboring multiple pathologies (↑amyloid, ↑tau, and ↓SV2A density) contributes to cognitive decline. Approach: The investigators will examine core indices of cognitive status and continuous measures of cognitive function from the source cohorts and utilize mixed effects models to ascertain the effect of UCB-J amyloid and tau on cognition.
- Specific Aim 4). Determine factors which impact synapse loss. Rationale: Several risk factors for cognitive decline and dementia have been identified including potentially modifiable factors such as insulin resistance and vascular risk factors. Approach: The investigators will determine cross-sectional and longitudinal trajectories of regional synapse loss in relation to risk factors for cognitive decline and dementia. In order to determine insulin resistance, the investigators will perform blood draw and assess fasting glucose and insulin values to determine the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The impact of potentially modifiable risk factors on synapse loss in vivo is currently unknown. This aim will address this gap in knowledge, results which may translate to strategies for reducing dementia risk.
- Conditions
- Alzheimer Disease
- Being tested
- UCB-J, MRI Scan, PET Scan
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UCB-JDrug
PET imaging with UCB-J
MRI ScanDevice
Also called Magnetic Resonance Imaging
MRI exams will be performed using a 3T MRI scanner, scan duration is typically 60 minutes
PET ScanDevice
Also called Positron Emission Tomography
PET imaging may be collected using either a PET scanner or a PET/Computed Tomography (CT) scanner, a PET scan will be initiated with the injection of radiotracer
| Study group | Role | What they receive |
|---|---|---|
| Cognitively Impaired plus Cognitive Unimpaired Participants | Experimental | Participants include both cognitively impaired and unimpaired populations to populate a single model to examine variables within the group as a whole.
* Cognitively impaired participants have abnormal cognitive status of MCI or dementia as judged by consensus or expert review using National Institute of Aging and Alzheimer's Association (NIA-AA) 2018 criteria.
* Cognitively unimpaired participants: results of most recent testing with the source cohort indicate the participant is cognitively unimpaired as judged by consensus or expert review. Receives: Drug: UCB-J; Device: MRI Scan; Device: PET Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
ROC AUCs (MCI/AD vs Cognitively Unimpaired (CU)) for Medial Temporal Lobe (MTL) UCB-J Distribution Volume Ratio (DVR) and Hippocampal Volume
DeLong's method will test whether the MTL UCB-J receiver-operator characteristic (ROC) area under the curve (AUC) has better mild cognitive impairment/probable AD dementia (MCI/AD) prediction accuracy than the hippocampal volume ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, hippocampal volume.
Measured: Baseline
ROC AUCs (MCI/AD vs CU) for MTL UCB-J and Hippocampal Cingulum Neurite Density Index
DeLong's method will test whether the MTL UCB-J ROC AUC has better MCI/AD prediction accuracy than the hippocampal cingulum neurite density index ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, hippocampal cingulum neurite density index.
Measured: Baseline
Annual Rate of Change in UCB-J DVR
Linear mixed effects regression will model UCB-J distribution volume ratio (DVR) as a function of time since baseline. 11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density. Participants' synaptic density was examined as a change per year. A positive number would mean an increase in synaptic density, a negative number means a decrease.
Measured: Baseline and 2 years
Baseline Diagnosis Group Differences in Annual Rate of Change in UCB-J DVR
Baseline diagnosis (CU vs MCI/probable AD dementia) group differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Participants' synaptic density was examined as a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that impaired participants decreased in synaptic density more quickly and a positive number would mean that the impaired participants decreased less quickly.
Measured: baseline and 2 years
Amyloid Positivity Status Differences in Annual Rate of Change in UCB-J DVR
Amyloid positivity status differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Amyloid positivity status will be determined from amyloid PET. Participants' synaptic density was examined in a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that amyloid positive participants decreased in synaptic density more quickly and a positive number would mean that the amyloid positive participants decreased less quickly.
Measured: baseline and 2 years
Tau Positivity Status Differences in Annual Rate of Change in UCB-J DVR
Tau positivity status differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Tau positivity status will be determined from tau PET. Participants' synaptic density was examined as a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that tau positive participants decreased in synaptic density more quickly and a positive number would mean that the tau positive participants decreased less quickly.
Measured: baseline and 2 years
MTL UCB-J DVR Baseline Differences in a Cognitive Performance Age Slope in Non-demented Participants
Linear mixed effects will be used to model cognitively unimpaired participants' memory performance as a function of their age and synaptic density. Specifically, investigators will test whether those with higher synaptic density had less deterioration over time. Memory performance will be assessed using Rey Auditory Verbal Learning Test Delayed Recall. An interaction was tested, and a negative number means that those with higher synaptic density decreased faster over time, and a positive number means that they decreased slower over time.
Measured: baseline and 2 years
Secondary outcomes (6)
Difference Between ROC AUCs (MCI/AD vs CU) for Medial Temporal Lobe (MTL) UCB-J Distribution Volume Ratio (DVR) and Cerebrospinal Fluid (CSF) Neurofilament Light Chain Protein (NfL)
DeLong's method will test whether the MTL UCB-J ROC AUC has better MCI/AD prediction accuracy than the cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, CSF NfL.
Measured: baseline
Difference Between ROC AUCs (MCI/AD vs CU) for MTL UCB-J DVR and Cerebrospinal Fluid (CSF) Total-tau (T-tau)
DeLong's method will test whether the MTL UCB-J ROC AUC has better MCI/AD prediction accuracy than the cerebrospinal fluid (CSF) T-tau ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, CSF T-tau.
Measured: baseline
Difference Between ROC AUCs (MCI/AD vs CU) for MTL UCB-J and CSF Neurogranin
DeLong's method will test whether the MTL UCB-J ROC AUC has better MCI/AD prediction accuracy than the cerebrospinal fluid (CSF) neurogranin ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, CSF neurogranin.
Measured: baseline
Sex Differences in Annual Rate of Change in UCB-J DVR
Sex differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Sex determined from self report. Participants' synaptic density was examined in a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that male participants decreased in synaptic density more quickly and a positive number would mean that the male participants decreased less quickly.
Measured: baseline and 2 years
Age Differences in Annual Rate of Change in UCB-J DVR
Linear mixed effects will be used to model all participants' UCB-J DVR trajectories as a function of their baseline age. Specifically, investigators will test whether those who were older at baseline had more deterioration over time. An interaction was tested, and a negative number means that those who were older at baseline decreased faster over time, and a positive number means that they decreased slower over time.
Measured: baseline and 2 years
APOE4 Allele Status Differences in Annual Rate of Change in UCB-J DVR
APOE4 allele status differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. APOE4 allele status determined from genetic testing. Participants' synaptic density was examined in a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that APOE4 positive participants decreased in synaptic density more quickly and a positive number would mean that the APOE4 positive participants decreased less quickly.
Measured: baseline and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2021
- Study start18 Nov 2018
- Primary completion17 Oct 2023
- Study completion1 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Barbara Bendlin, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04871074
- Sponsor's protocol ID
- 2018-1283
- Other IDs
- A534255, SMPH/MEDICINE/GER-AD DEV, Protocol Version 3/7/2024, R01AG062285
- Status last verified
- Jun 2026
- First submitted
- 28 Apr 2021
- Last updated
- 26 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SV2A PET Imaging in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04871074
- Acronym / sponsor ID
- 2018-1283
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 18 Nov 2018 (actual)
- Primary completion
- 17 Oct 2023 (actual)
- Study completion
- 1 May 2025 (actual)
- First posted
- 4 May 2021 (actual)
- Results
- Posted 12 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overarching goal of this project is to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform Alzheimer's disease (AD) progression. The investigators propose to collect longitudinal amyloid, tau, and Synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) in participants in the Wisconsin Alzheimer's Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer's Prevention (WRAP) across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, mild cognitive impairment (MCI), and dementia due to AD.
Detailed description
Synaptic loss is a major feature of symptomatic AD. Conversely, abundance of synapses may confer resilience to cognitive decline in the presence of AD pathology. The pathology-defining features of AD are amyloid plaques and neurofibrillary tangles and their presence and distribution can be spatially estimated in-vivo with amyloid and tau PET. Although these biomarkers can inform on the degree and location of pathology, they do not provide an indicator of their effect on collocated or extended in-network neural damage including synaptic density.
SV2A is expressed ubiquitously in synapses and the capability of assessing SV2A in vivo may provide a direct indicator of synaptic health. Such information would be of high importance for staging the level of synaptic loss or conversely synaptic abundance in the AD continuum and may potentially improve prognostic precision. The PET radioligand [C-11]UCB-J is a marker of SV2A.
The overarching goal of this project is to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform upon disease progression. The investigators propose to collect longitudinal amyloid, tau, and SV2A PET in participants in the Wisconsin ADRC and WRAP across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, MCI, and dementia due to AD.
- Specific Aim 1). Determine the extent to which [C-11]UCB-J provides unique information from MRI regarding neurodegeneration. Approach: The investigators will recruit N=60 cognitively unimpaired participants, N=30 MCI participants, and N=30 participants with AD dementia to undergo PET imaging with [C-11]UCB-J. MRI will include anatomic and diffusion connectivity MRI. When available, ancillary cerebrospinal fluid (CSF) indicators of neurodegeneration and synapse function will be examined for relationships with UCB-J.
- Specific Aim 2). Determine the rate of synapse loss as reflected by [C-11]UCB-J signal across all participants. Rationale: Trajectories of synaptic loss are unknown in vivo. Approach: The investigators will determine the longitudinal trajectories of regional synapse loss that are observed over time among participants who undergo repeat [C-11]UCB-J (separated by two years, same participants scanned for Aim 1). The investigators will also examine trajectories by amyloid and tau load. Quantifying longitudinal synaptic loss is expected to eventually facilitate the identification of individuals who are progressing to dementia, as well as inform upon changes that are normal for age.
- Specific Aim 3). Determine the extent to which [C-11]UCB-J associates with cognitive decline. Rationale: The investigators expect that lower baseline SV2A density and longitudinal decline in SV2A density in the medial temporal lobe will be associated with faster progression of cognitive decline. The investigators will also test the extent to which harboring multiple pathologies (↑amyloid, ↑tau, and ↓SV2A density) contributes to cognitive decline. Approach: The investigators will examine core indices of cognitive status and continuous measures of cognitive function from the source cohorts and utilize mixed effects models to ascertain the effect of UCB-J amyloid and tau on cognition.
- Specific Aim 4). Determine factors which impact synapse loss. Rationale: Several risk factors for cognitive decline and dementia have been identified including potentially modifiable factors such as insulin resistance and vascular risk factors. Approach: The investigators will determine cross-sectional and longitudinal trajectories of regional synapse loss in relation to risk factors for cognitive decline and dementia. In order to determine insulin resistance, the investigators will perform blood draw and assess fasting glucose and insulin values to determine the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The impact of potentially modifiable risk factors on synapse loss in vivo is currently unknown. This aim will address this gap in knowledge, results which may translate to strategies for reducing dementia risk.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cognitively Impaired plus Cognitive Unimpaired Participants | Experimental | Drug: UCB-J, Device: MRI Scan, Device: PET ScanParticipants include both cognitively impaired and unimpaired populations to populate a single model to examine variables within the group as a whole. * Cognitively impaired participants have abnormal cognitive status of MCI or dementia as judged by consensus or expert review using National Institute of Aging and Alzheimer's Association (NIA-AA) 2018 criteria. * Cognitively unimpaired participants: results of most recent testing with the source cohort indicate the participant is cognitively unimpaired as judged by consensus or expert review. |
Who may qualify
- Ages
- 55 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Cognitively unimpaired adults-
- Mild dementia and amnestic Mild Cognitive Impairment-
Key exclusion criteria (11 listed)
- For women, pregnant, lactating or breastfeeding, or intention to become pregnant
- Evidence of unstable or untreated clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Stable, treated chronic medical conditions like hypertension, hypercholesterolemia, diabetes mellitus, non-metastatic dermatologic or prostatic cancer, etc. are acceptable as long as they do not, in the study investigator's opinion, contribute to cognitive dysfunction or limit participation in study procedures.
- Any illness or other consideration that makes it unlikely that the subject will be able to complete the 24-month study.
- Current or prior history (within past 5 years) of significant alcohol or substance abuse as determined by the investigator.
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 |
|---|---|---|
| UCB-JPET imaging with UCB-J | Drug | Cognitively Impaired plus Cognitive Unimpaired Participants |
| MRI ScanAlso: Magnetic Resonance ImagingMRI exams will be performed using a 3T MRI scanner, scan duration is typically 60 minutes | Device | Cognitively Impaired plus Cognitive Unimpaired Participants |
| PET ScanAlso: Positron Emission TomographyPET imaging may be collected using either a PET scanner or a PET/Computed Tomography (CT) scanner, a PET scan will be initiated with the injection of radiotracer | Device | Cognitively Impaired plus Cognitive Unimpaired Participants |
Primary outcome
ROC AUCs (MCI/AD vs Cognitively Unimpaired (CU)) for Medial Temporal Lobe (MTL) UCB-J Distribution Volume Ratio (DVR) and Hippocampal Volume
Time frame: Baseline
DeLong's method will test whether the MTL UCB-J receiver-operator characteristic (ROC) area under the curve (AUC) has better mild cognitive impairment/probable AD dementia (MCI/AD) prediction accuracy than the hippocampal volume ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, hippocampal volume.
ROC AUCs (MCI/AD vs CU) for MTL UCB-J and Hippocampal Cingulum Neurite Density Index
Time frame: Baseline
DeLong's method will test whether the MTL UCB-J ROC AUC has better MCI/AD prediction accuracy than the hippocampal cingulum neurite density index ROC AUC. ROC AUC is a measure of the correctness of group (where group is MCI/AD and cognitively unimpaired) classification using a continuous predictor, in this case, the medial temporal lobe UCB-J uptake (11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density). This ROC AUC was compared to that of the comparator continuous predictor, hippocampal cingulum neurite density index.
Annual Rate of Change in UCB-J DVR
Time frame: Baseline and 2 years
Linear mixed effects regression will model UCB-J distribution volume ratio (DVR) as a function of time since baseline. 11C-UCB-J is a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the human brain. It is considered a measure of synaptic density. Participants' synaptic density was examined as a change per year. A positive number would mean an increase in synaptic density, a negative number means a decrease.
Baseline Diagnosis Group Differences in Annual Rate of Change in UCB-J DVR
Time frame: baseline and 2 years
Baseline diagnosis (CU vs MCI/probable AD dementia) group differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Participants' synaptic density was examined as a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that impaired participants decreased in synaptic density more quickly and a positive number would mean that the impaired participants decreased less quickly.
Amyloid Positivity Status Differences in Annual Rate of Change in UCB-J DVR
Time frame: baseline and 2 years
Amyloid positivity status differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Amyloid positivity status will be determined from amyloid PET. Participants' synaptic density was examined in a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that amyloid positive participants decreased in synaptic density more quickly and a positive number would mean that the amyloid positive participants decreased less quickly.
Tau Positivity Status Differences in Annual Rate of Change in UCB-J DVR
Time frame: baseline and 2 years
Tau positivity status differences in rate of UCB-J DVR change will be estimated via group x time interaction term in a linear mixed effects model. Tau positivity status will be determined from tau PET. Participants' synaptic density was examined as a change per year. The difference in the rate of change in the two groups was estimated. A negative number means that tau positive participants decreased in synaptic density more quickly and a positive number would mean that the tau positive participants decreased less quickly.
MTL UCB-J DVR Baseline Differences in a Cognitive Performance Age Slope in Non-demented Participants
Time frame: baseline and 2 years
Linear mixed effects will be used to model cognitively unimpaired participants' memory performance as a function of their age and synaptic density. Specifically, investigators will test whether those with higher synaptic density had less deterioration over time. Memory performance will be assessed using Rey Auditory Verbal Learning Test Delayed Recall. An interaction was tested, and a negative number means that those with higher synaptic density decreased faster over time, and a positive number means that they decreased slower over time.
6 secondary outcomes
Difference Between ROC AUCs (MCI/AD vs CU) for Medial Temporal Lobe (MTL) UCB-J Distribution Volume Ratio (DVR) and Cerebrospinal Fluid (CSF) Neurofilament Light Chain Protein (NfL)
Time frame: baseline
Difference Between ROC AUCs (MCI/AD vs CU) for MTL UCB-J DVR and Cerebrospinal Fluid (CSF) Total-tau (T-tau)
Time frame: baseline
Difference Between ROC AUCs (MCI/AD vs CU) for MTL UCB-J and CSF Neurogranin
Time frame: baseline
Sex Differences in Annual Rate of Change in UCB-J DVR
Time frame: baseline and 2 years
Age Differences in Annual Rate of Change in UCB-J DVR
Time frame: baseline and 2 years
APOE4 Allele Status Differences in Annual Rate of Change in UCB-J DVR
Time frame: baseline and 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
Recruiting
Transcranial Alternating Current Stimulation (tACS) Combined With Cognitive Training in Alzheimer's Disease
Transcranial Alternating Current Stimulation, Alzheimer Disease (AD)
Not yet recruiting
Exercise in Alzheimer's Disease: Functional Biomarkers
Alzheimer's Dementia (AD), Alzheimer Disease (AD)
RecruitingObservational study
PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)
Aging
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.
Barbara Bendlin, PhD principal investigator
University of Wisconsin, Madison
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 UCB-J, MRI Scan and PET Scan in people with Alzheimer Disease, run by University of Wisconsin, Madison 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 12 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: finished, as of the sponsor's last update on 26 Jun 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?
Yes. Results are posted in the registry (first posted 12 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
ROC AUCs (MCI/AD vs Cognitively Unimpaired (CU)) for Medial Temporal Lobe (MTL) UCB-J Distribution Volume Ratio (DVR) and Hippocampal Volume (time frame: Baseline). The study lists 7 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 26 Jun 2026.