Synaptic Imaging for Schizophrenia

Recruiting at 1 trial location

Overseen By Study Coordinator 2

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Davidzon, Guido, M.D.

Must be taking: Antipsychotics

Disqualifiers: Substance use, Neurological illness, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore brain changes in people with schizophrenia by using a special PET scan to measure synapse numbers (connections between nerve cells). Researchers believe that excessive synapse removal might contribute to schizophrenia. The study will include two groups: individuals with schizophrenia and healthy individuals, both undergoing PET scans with the [11C]UCB-J radiotracer. Those with a stable diagnosis of schizophrenia and consistent medication for at least two weeks might qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that participants with schizophrenia be on a stable medication regimen for at least two weeks before testing, so you will not need to stop taking your current medications.

What prior data suggests that this imaging method is safe?

Research shows that the [11C]UCB-J tracer, used for brain scans, is generally safe for people. Some studies have explored how this tracer works, particularly its ability to show the number of connections between nerve cells in the brain. These studies have not identified any major safety concerns or serious side effects from using [11C]UCB-J.

In one study, researchers used the tracer to compare the brains of people with schizophrenia to those of healthy individuals. The results did not reveal any significant safety issues with the tracer. Another study confirmed that [11C]UCB-J works well for its intended purpose without major risks.

Since this is an early-phase trial, the main goal is to assess the tracer's safety for humans. Early-phase trials often test a treatment's safety for the first time, and so far, the findings are promising for the safety of [11C]UCB-J. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of the [11C]UCB-J radiotracer for schizophrenia imaging because it offers a new way to visualize synaptic density in the brain. Unlike current treatments that primarily focus on managing symptoms through medications like antipsychotics, [11C]UCB-J targets synaptic vesicle glycoprotein 2A (SV2A), giving researchers a direct look at synaptic changes associated with schizophrenia. This could lead to better understanding and potentially more effective interventions for the condition by providing precise insights into how the brain's synapses are functioning.

What evidence suggests that this imaging method is effective for studying schizophrenia?

Research has shown that the [11C]UCB-J radiotracer is a promising tool for studying connections between brain cells. It helps visualize the loss of these connections in conditions like mild cognitive impairment and Alzheimer's disease. In this trial, participants with schizophrenia will undergo imaging with [11C]UCB-J to measure the decrease in these connections, a well-known finding in schizophrenia. This imaging tool could support the idea that excessive loss of these connections contributes to schizophrenia, potentially leading to new diagnostic and treatment methods for the condition. ^{1 4 6 7 8}

Who Is on the Research Team?

Jong H Yoon, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with a clinical diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder. Participants must be on stable medication for at least two weeks and able to undergo a PET-MR scan without sedation.

Inclusion Criteria

I have been diagnosed with schizophrenia or a related disorder.

I can undergo a PET-MR scan without needing sedation.

My medication has not changed in the last two weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the [11C]UCB-J radiotracer

120 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [11C]UCB-J radiotracer

Trial Overview The study uses [11C]UCB-J radiotracer in a PET-MR imaging technique to measure synaptic density in the brain and test the neural synaptic pruning hypothesis related to schizophrenia.

How Is the Trial Designed?

Group I: Schizophrenia (SZ) Participants Experimental Treatment 2 Interventions

Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the \[11C\]UCB-J radiotracer

Group II: Healthy Control (HC) Participants Experimental Treatment 2 Interventions

Participants will undergo positron emission tomography-magnetic resonance (PET-MR) imaging using the \[11C\]UCB-J radiotracer

Who Is Running the Clinical Trial?

Davidzon, Guido, M.D.

Lead Sponsor

Trials

3

Recruited

60+

Weston Havens Foundation

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

A comprehensive review of 18 meta-analyses involving over 50,000 subjects indicates that schizophrenia is linked to lower grey matter volumes, cortical thickness, and abnormal brain structure, suggesting significant synaptic alterations.

Key brain regions affected include the frontal, anterior cingulate, and temporal cortices, as well as the hippocampi, with evidence pointing towards lower synaptic density in these areas compared to healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes. Howes, OD., Cummings, C., Chapman, GE., et al.[2023]

In a study of 42 participants (21 with schizophrenia and 21 healthy volunteers), no significant differences in synaptic terminal density were found early in schizophrenia, suggesting that major changes in synaptic density may develop later in the illness.

However, subtle reductions in synaptic terminal density were observed in specific brain regions, such as the temporal lobe and anterior cingulate cortex, indicating that early synaptic changes may still occur in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synaptic Terminal Density Early in the Course of Schizophrenia: An In Vivo UCB-J Positron Emission Tomographic Imaging Study of Synaptic Vesicle Glycoprotein 2A. Onwordi, EC., Whitehurst, T., Shatalina, E., et al.[2023]

The study assessed the radiation dosimetry of the radioligand 11C-UCB-J in four healthy adults, finding that it is safe for use in both adults and adolescents to measure synaptic density, which is important for understanding neuropsychiatric disorders.

The urinary bladder was identified as the dose-limiting organ for adult males, while the liver was the limit for adult females, and the large intestine for adolescents, indicating specific safety considerations for different demographics when using this imaging technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J. Bini, J., Holden, D., Fontaine, K., et al.[2023]

In a study involving 18 patients with schizophrenia and 18 controls, researchers found significantly lower levels of synaptic vesicle glycoprotein 2A (SV2A) in the frontal and anterior cingulate cortices of patients, suggesting a link between synaptic dysfunction and schizophrenia symptoms.

The study also showed that antipsychotic medications did not significantly affect SV2A levels in rats, indicating that the observed lower levels in schizophrenia are not due to medication effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats. Onwordi, EC., Halff, EF., Whitehurst, T., et al.[2023]

The newly developed PET radiotracer [18F]UCB-J, with a longer half-life of 110 minutes, shows promising pharmacokinetic properties and high brain uptake in nonhuman primates, making it a potential tool for studying synaptic abnormalities in neuropsychiatric disorders.

[18F]UCB-J demonstrated imaging characteristics similar to the previously developed [11C]UCB-J, indicating its effectiveness for in vivo imaging of synaptic vesicle glycoprotein 2A (SV2A) and potentially aiding in the diagnosis and understanding of conditions like epilepsy and Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A). Li, S., Cai, Z., Zhang, W., et al.[2020]

Patients with schizophrenia showed significantly lower synaptic vesicle density, as measured by the PET ligand [11C]UCB-J, across multiple brain regions compared to healthy controls, indicating a potential biomarker for the disease.

The study found that lower synaptic vesicle density in the frontal cortex was associated with more severe psychotic symptoms and poorer cognitive performance, suggesting a link between synaptic health and the severity of schizophrenia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo evidence of lower synaptic vesicle density in schizophrenia. Radhakrishnan, R., Skosnik, PD., Ranganathan, M., et al.[2023]

In a study involving 18 participants (9 with schizophrenia and 9 healthy controls), significant reductions in synaptic binding were observed in early-course schizophrenia patients, supporting the hypothesis of excess synaptic pruning as a key mechanism in the disease.

The findings showed widespread synaptic deficits in specific brain regions, correlating with cognitive performance and severity of delusions, indicating that these synaptic binding deficits are consistent and may be present even in the early stages of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reductions in synaptic marker SV2A in early-course Schizophrenia. Yoon, JH., Zhang, Z., Mormino, E., et al.[2023]

The radioligand [11C]UCB-J selectively binds to synaptic vesicle glycoprotein 2A (SV2A) in mice, demonstrating its potential as a tool for measuring synaptic density in brain disorders.

The study confirmed that [11C]UCB-J has optimal kinetics for imaging, with a 60-minute scan duration being sufficient for reliable quantification, making it a promising method for investigating neuropsychiatric and neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation and noninvasive kinetic modeling of [11C]UCB-J PET imaging in mice. Bertoglio, D., Verhaeghe, J., Miranda, A., et al.[2021]

Citations

1. biorxiv.org biorxiv.org/content/10.1101/2024.09.25.614893v1.full.pdf

a combined [11C]UCB-J PET and fMRI study In control subjects, there was a significant positive. 62 relationship between [11C]UCB-J distribution volume ratio (DVRcs) and ALFF in the ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/437270

Imaging Synapses With [11C] UCB-J in the Human Brain The purpose of this study is to utilize the radioactive positron emission tomography (PET) tracer \[11C\]UCB-J to test the neural synaptic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6339829/

PET Imaging of Synaptic Density: A New Tool for Investigation ... A SV2A PET imaging study using [11C]UCB-J in 10 MCI/AD patients and 11 age-matched cognitively normal subjects demonstrated significant synapse loss in the ...

4. analyticalsciencejournals.onlinelibrary.wiley.com analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jlcr.3828

Automated radiosynthesis of [11C]UCB‐J for imaging synaptic ... The nondecay corrected radiochemical yield was 11 ± 1% (n = 7) and if decay corrected 35 ± 4% (n = 7). The QC analysis of the produced [11C]UCB- ...

5. researchgate.net researchgate.net/figure/Comparison-of-synaptic-densityCUCB-J-BPND-in-schizophreniaSCZ-and-healthy_fig1_352453219

Comparison of synaptic density ([¹¹C]UCB-J BPND) in ... Decreased synaptic spine density has been the most consistently reported postmortem finding in schizophrenia (SCZ). A recently developed in vivo measure of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37330164/

An In Vivo UCB-J Positron Emission Tomographic Imaging ... These findings indicate that large differences in synaptic terminal density are not present early in SCZ, although there may be more subtle effects.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006322323013537

An In Vivo UCB-J Positron Emission Tomographic Imaging ... Therefore, we conducted a clinical imaging study using [11C]UCB-J positron emission tomography (PET) to test the hypothesis that [11C]UCB-J ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03995121

NCT03995121 | SV2 PET Imaging With [11C]APP311 The aim of this study is to evaluate a new SV2A tracer, [11C]APP311, in healthy aging and neuropsychiatric disorders including psychotic disorders and cannabis ...