UCB-J for Alzheimer's Disease

Overseen By Mary-Elizabeth Pasquesi

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must not be taking: Levetiracetam

Disqualifiers: Pregnancy, Alcohol abuse, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand Alzheimer's disease by examining brain synapses (connections between nerve cells) using a special imaging technique called UCB-J. It tracks changes in the brain's structure over time in individuals at different stages of Alzheimer's, from no symptoms to dementia. Participants with mild memory issues or those who are cognitively healthy are needed and must be willing to undergo a few specific brain scans. These scans will help researchers learn more about Alzheimer's progression, potentially leading to better treatments in the future. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potential breakthroughs in Alzheimer's care.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using the anti-seizure medication Levetiracetam. Stable, treated chronic conditions are generally acceptable if they don't affect cognition or participation.

What prior data suggests that UCB-J is safe for use in Alzheimer's research?

Research has shown that UCB-J is safe for humans. One study found it has a low radiation dose when used as a PET imaging agent, making it suitable for repeated brain scans. This indicates it is generally well-tolerated for brain imaging.

Another study found UCB-J promising for tracking brain changes related to Alzheimer's disease, suggesting it does not cause significant side effects for this purpose. Although detailed safety data for Alzheimer's patients is not available, its use in other research without major side effects is reassuring. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike current treatments for Alzheimer's disease, which typically focus on managing symptoms with medications like donepezil or memantine, UCB-J is unique because it aims to provide insights into the disease's progression by targeting specific biomarkers in the brain. Researchers are excited about UCB-J because it uses a novel imaging agent that binds to tau proteins, which are associated with Alzheimer's disease, potentially allowing for earlier and more accurate diagnosis. This approach could not only improve understanding of the disease but also lead to more personalized and effective treatment strategies in the future.

What evidence suggests that UCB-J might be an effective treatment for Alzheimer's?

Research has shown that UCB-J is promising for detecting brain changes related to Alzheimer's disease. Studies have found that individuals with mild cognitive impairment or early Alzheimer's experience a 41% decrease in synaptic density, which this method can measure. Synaptic loss is a key factor in Alzheimer's and is linked to memory problems. In this trial, participants, both cognitively impaired and unimpaired, will undergo assessment using UCB-J to examine synaptic density. Researchers have identified lower synaptic density in important brain areas like the hippocampus using UCB-J. This finding suggests that UCB-J could help track Alzheimer's progression by highlighting these changes in the brain. ^{6 7 8 9 10}

Who Is on the Research Team?

Barbara Bendlin, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adults aged 50-89 with Alzheimer's Disease, ranging from normal cognition to mild dementia. Participants must be willing to undergo specific PET scans and have a recent MRI. Exclusions include pregnancy, substance abuse history, major psychiatric disorders, MRI-incompatible implants, or conditions that could affect cognition or study completion.

Inclusion Criteria

Normal cognition (results of most recent testing with the source cohort indicate the participant is cognitively unimpaired as judged by consensus or expert review)

I am willing to have specific PET scans for my condition.

I have mild memory loss or mild dementia.

Exclusion Criteria

I am currently taking Levetiracetam for seizures.

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial PET imaging and cognitive assessments are conducted to establish baseline measurements

1-2 weeks

1 visit (in-person)

Longitudinal Imaging

Participants undergo repeat PET imaging to assess synapse loss and cognitive decline over time

2 years

Multiple visits (in-person) over 2 years

Follow-up

Participants are monitored for changes in cognitive function and synaptic density

6 months

What Are the Treatments Tested in This Trial?

Interventions

• UCB-J

Trial Overview [C-11]UCB-J is being tested in The Synapse Project to track neuronal synapse density and understand Alzheimer's progression. Participants will receive longitudinal amyloid, tau, and SV2A PET imaging across various stages of cognitive impairment within the Wisconsin Alzheimer's research cohorts.

How Is the Trial Designed?

Group I: Cognitively Impaired plus Cognitive Unimpaired Participants Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2213158223001468

Principal component analysis of synaptic density measured ... Synaptic loss is considered an early pathological event and major structural correlate of cognitive impairment in Alzheimer's disease (AD).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6894376/

In Vivo Synaptic Density Imaging with 11C-UCB-J Detects ... Recently, we conducted 11C-UCB-J PET on patients with mild cognitive impairment or early Alzheimer disease (AD) and found a 41% decrease in specific binding ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/62/supplement_1/119

[C-11]UCB-J uptake and Ab accumulation across the cognitive ... Results: Among participants with cognitive impairment, [11C]UCB-J DVR was lower in the hippocampus (0.54 ± 0.07) relative to the cognitively ...

4. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-020-00742-y

Association of Aβ deposition and regional synaptic density in ... In our subsequent study of [11C]UCB-J in early AD in a larger cohort, we observed more extensive cortical and subcortical reductions in SV2A ...

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12097

In vivo measurement of widespread synaptic loss in ... Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11848344/

Post mortem validation and mechanistic study of UCB‐J in ... We report an in‐depth post mortem validation and mechanistic study of UCB‐J in PSP and control brains using radioligand/autoradiography binding studies.

7. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13720

Tracing synaptic loss in Alzheimer's brain with SV2A PET ... The recently developed novel synaptic vesicle 2A protein (SV2A) PET-tracer UCB-J has shown great promise in tracking synaptic loss in AD.

8. ejnmmiphys.springeropen.com ejnmmiphys.springeropen.com/articles/10.1186/s40658-021-00384-5

Human biodistribution and dosimetry of [11C]-UCB-J, a PET ... Clinical use of [11C]-UCB-J is safe and results in an ED of 5.1 ± 0.8 μSv/MBq, confirming previous findings and allowing multiple serial PET ...

9. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-024-01382-2

A pilot study to evaluate the effect of CT1812 treatment on ... CT1812 was found to be generally safe and well tolerated in a placebo-controlled phase 1 clinical trial in healthy volunteers and phase 1a/2 ...

10. clinicaltrials.eu clinicaltrials.eu/inn/ucb-j/

UCB-J: A Novel Imaging Agent for Brain Research This article explores the use of UCB-J in various clinical trials, focusing on its potential to measure synaptic density in conditions such as schizophrenia, ...