Imaging Techniques for Depression and Bipolar Disorder

Overseen By Sarah O'Grady, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Anticoagulants

Disqualifiers: Significant medical disorder, Suicidal ideation, Pregnancy, Substance use, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the involvement of the brain's glutamate system and synaptic connections in depression and bipolar disorder. Participants will undergo brain scans (such as MRI and PET) and cognitive tests to aid researchers in understanding these conditions better. The study examines two substances, [11C]APP311 (an imaging agent) and [18F]FPEB, to assess their effects on brain activity. Individuals diagnosed with major depressive disorder or bipolar disorder might be suitable for this trial. As an unphased trial, it offers participants a unique opportunity to contribute to groundbreaking research that could enhance the understanding and treatment of these mental health conditions.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team during the screening appointment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both investigational treatments, [11C]APP311 and [18F]FPEB, have promising safety records in humans.

[11C]APP311, also known as [11C]UCB-J, is a PET scan tracer used to view brain connections. Studies indicate it is safe for humans, as the kidneys and liver process it without issues. No significant side effects have been reported, making it well-tolerated.

Similarly, [18F]FPEB is another PET scan tracer that helps image certain brain receptors. Research indicates this treatment is safe and well-tolerated. Safety tests after its use showed no major problems, suggesting it is generally safe for humans.

Previous studies have tested both treatments and have not shown any major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative imaging techniques to better understand psychiatric disorders like major depressive disorder (MDD) and bipolar disorder. While current treatments often focus on balancing neurotransmitters or mood stabilization through medications like SSRIs or mood stabilizers, this trial uses [11C]APP311 and [18F]FPEB PET scans to visualize synaptic density and mGluR5 receptor activity in the brain. By offering a clearer picture of brain function and changes, these imaging agents could lead to more personalized and effective treatment strategies in the future.

What evidence suggests that this trial's treatments could be effective for depression and bipolar disorder?

In this trial, participants will undergo PET scans using either [11C]APP311 or [18F]FPEB. Research has shown that [11C]APP311 aids in understanding changes in brain connections related to depression and bipolar disorder. Animal studies indicate that depression and stress can alter the brain's structure, which [11C]APP311 can detect. This enables researchers to observe changes in brain cell connections.

For [18F]FPEB, studies suggest it targets a brain receptor called mGluR5, linked to mood disorders. This could help differentiate between depression and bipolar disorder. It may also address symptoms of depression and improve cognitive function. These findings provide a basis for how these treatments might work in studying mental health conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Irina Esterlis, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Inclusion Criteria

-Inclusion criteria for healthy controls: no current, or history of any DSM-5 diagnosis

Inclusion criteria for MDD subjects clinical diagnosis of major depressive disorder

Inclusion criteria for bipolar subjects clinical diagnosis of bipolar disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging and Testing

Participants undergo MRI or fMRI scans, MRS scans, PET scans, and cognitive testing

1-2 months

2-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and testing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [11C]APP311
• [18F]FPEB

How Is the Trial Designed?

Group I: MDD Experimental Treatment 2 Interventions

30 subjects with major depressive disorder (MDD) may participate in MRI or fMRI, \[1H\]MRS and/or \[13C\]MRS, \[18F\]FPEB and/or \[11C\]APP311 PET scans, cognitive testing

Group II: Healthy control Experimental Treatment 2 Interventions

60 psychiatrically-healthy subjects will be enrolled as controls may participate in MRI or fMRI, \[1H\]MRS and/or \[13C\]MRS, \[18F\]FPEB and/or \[11C\]APP311 PET scans, cognitive testing

Group III: Bipolar Experimental Treatment 2 Interventions

30 subjects with bipolar disorder may participate in MRI or fMRI, \[1H\]MRS and/or \[13C\]MRS, \[18F\]FPEB and/or \[11C\]APP311 PET scans, cognitive testing

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10119194/

PET imaging of animal models with depressive-like phenotypes ... depressive symptoms [138]. [11C]UCB-J -PET data can also serve as an input for connectivity studies to describe brain networks [139], which suggest a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03898297

NCT03898297 | Imaging mGluR5 and Synaptic Density in ... Synaptic density and [11C]APP311: There is strong preclinical evidence showing that chronic stress and depression lead to structural changes, which include ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0969805122020662

Healthy brain aging assessed with [18F]FDG and [11C] ... The aim of this study was to assess healthy brain aging using [ 18 F]FDG as a measure of cerebral glucose consumption and [ 11 C]UCB-J PET as an indicator of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8049341/

Simplified Quantification of 11C-UCB-J PET Evaluated in a ... Conclusion: The 60- to 90-min period provided the best match between SUVR-1 and BPND (−1% ± 7%); thus, a short scan is sufficient for accurate ...

5. researchgate.net researchgate.net/publication/395414218_Motor_signs_in_late_life_depression_relate_to_altered_subcortical_synaptic_density_and_gray_matter_volume_an_11C-UCB-J_PET-MR_study

Motor signs in late life depression relate to altered ... Motor signs in late life depression relate to altered subcortical synaptic density and gray matter volume: an 11C-UCB-J PET-MR study. September ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03995121

NCT03995121 | SV2 PET Imaging With [11C]APP311 It has been shown that radiotracer [11C]APP311 (aka [11C]UCB-J) displays high specificity and selectivity for the synaptic vesicle protein SV2A. Since this ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8065069/

UCB-J, a PET radiotracer for imaging synaptic density [11C]-UCB-J administration was safe and showed mixed renal and hepatobiliary clearance, with largest organ absorbed dose coefficients for the ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0001299824000667

Toward Functional PET Imaging of the Spinal Cord [11C]UCB-J is a PET radiotracer with high affinity for synaptic vesicle glycoprotein 2A (SV2A), a presynaptic protein regulating neurotransmitter release. Three ...

9. researchgate.net researchgate.net/publication/351084959_Human_biodistribution_and_dosimetry_of_11C-UCB-J_a_PET_radiotracer_for_imaging_synaptic_density

Human biodistribution and dosimetry of [11C]-UCB-J, a ... Results: [11C]-UCB-J administration was safe and showed mixed renal and hepatobiliary clearance, with largest organ absorbed dose coefficients ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6259313/

Kinetic evaluation and test–retest reproducibility of [11C ... 11 C UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative ...