Characterizing Synaptic Density in Treatment Resistant Depression (TPET)

August 27, 2026 updated by: Unity Health Toronto
The purpose of this study is to better understand how certain brain systems work in people with depression, especially in those whose symptoms have not improved with antidepressant treatments. We are particularly interested in synaptic density, which helps us understand how different parts of the brain communicate with each other. Synaptic density levels have implications on overall brain function and cognition. By comparing brain function in people with treatment-resistant depression, people with treatment-responsive depression, and healthy controls, we hope to better understand why some individuals do not respond to antidepressants. This research may help guide the development of more effective treatments in the future.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This research project examines synaptic density in the brain. Synaptic density refers to the number of communication connections that exist between brain cells in a given area, which provides researchers with information about how efficiently brain regions communicate. Researchers are studying synaptic density to better understand how brain communication may differ in people with depression.

It is estimated that 30% of individuals with Major depressive Disorder (MDD) fail to respond to conventional antidepressant medication. Treatment resistant depression (TRD) patients also are more likely to have other psychiatric and medical diagnoses, poorer quality of life, and increased suicidal ideation. There are few treatment strategies available to target TRD and there is not a lot of evidence about how TRD differs from depression that responds to treatment.

In this study, we will be collecting detailed information about your psychiatric history and depression symptoms, as well as two brain scans using positron emission tomography (PET) and magnetic resonance imaging (MRI). PET imaging uses a radioactive agent (also called a tracer) to obtain pictures of the brain. The tracer we will use is called [18F]- SynVesT-1, which measures synaptic density. In addition, the MRI scan will be used to examine your brain function when performing tasks involved in memory and learning about rewards. The ultimate goal of this study is to better understand synaptic density in your brain and how it relates to brain function during memory and reward learning tasks. This information will be important for advancing our knowledge of the brain biology of TRD and potential new areas for treatment development.

Study Type

Observational

Enrollment (Estimated)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ariel Graff-Guerrero, MD, PhD
  • Phone Number: 34834 416-535-850
  • Email: ariel.graff@camh.ca

Study Contact Backup

  • Name: Sakina J Rizvi, PhD
  • Phone Number: 6489 416-864-6060
  • Email: rizvis@smh.ca

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5B 1M4
        • Recruiting
        • Unity Health Toronto
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sakina J Rizvi, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 55 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited from clinics at St. Michael's Hospital and the Centre for Addiction and Mental Health as well as from research programs at the two sites, which have ongoing MDD clinical trials where patients are required to be unmedicated prior to initiating treatment.

Description

Inclusion Criteria:

  • Key inclusion criteria for the MDD patients:

    • DSM-5 criteria for a Major Depressive Episode (MDE) within a MDD, confirmed through MINI diagnosis (Sheehan et al, 2015)
    • Age between 25 and 65 years
    • Hamilton Depression Rating Scale - 17 item (HRSD-17; Hamilton, 1960) > 14 (moderate to severe symptoms)
    • Free of psychotropic medications (with the exception of SSRIs or SNRIs) for at least 5 half-lives before PET scanning per investigator discretion, after which an insignificant amount of drug is circulating through the body and accessing the brain. This determination will be based on self-report from the participant of when their last dose was. Use of benzodiazepines (except for diazepam) or sedative hypnotics (e.g. zopiclone) is allowable, but the last dose must be at least 72 hours prior to scanning.
    • Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)
    • For non-resistant patients: Previous history of response to an antidepressant, in order to increase signal to noise between resistant and non-resistant patients

Key inclusion criteria for the Healthy Controls:

  • Ages between 25 and 65 years
  • Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)

Exclusion Criteria:

Key exclusion criteria for the MDD patients:

  • Pregnancy/lactation
  • Medical condition requiring immediate investigation or treatment
  • Recent (< 6 months)/current history of drug abuse/dependence
  • Lifetime history of psychosis, other Axis I comorbidities are allowable
  • Use of any psychotropic use within 5 half-lives before the PET scanning, with the exception of SSRIs and SNRIs
  • For non-resistant patients: Failure of > 2 antidepressant treatments of adequate dose and duration for current MDE.

Key exclusion criteria for the Healthy Controls:

  • Pregnancy/lactation
  • Medical condition requiring immediate investigation or treatment
  • Lifetime history of any psychiatric disorder
  • Lifetime history of receiving an antidepressant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Treatment Resistant Depression
Unmedicated Individuals with Treatment Resistant Depression
Diagnostic test: PET scans
PET scans and PHNO scans
Major Depressive Disorder
Unmedicated Individuals with Major Depressive Disorder
Diagnostic test: PET scans
PET scans and PHNO scans
Healthy Control
healthy controls with no previous psychiatric disorders
Diagnostic test: PET scans
PET scans and PHNO scans

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Synaptic Density
Time Frame: 3 years
Synaptic density represents a promising biomarker for TRD, as it provides a direct index of neural circuit integrity and synaptic architecture (Appelbaum et al, 2022; Serano et al, 2022). Interventions shown to be effective in treatment-resistant populations, including rapid-acting antidepressants and neuromodulatory approaches, have been proposed to engage in synaptic plasticity-related mechanisms (Duman et al, 2016). As such, synaptic density measured using SV2A PET may offer insight into circuit-level abnormalities relevant to depression severity and treatment resistance, therefore offering a mechanistically informed approach for characterizing the biological correlates of TRD and supports its use in PET-based investigations of this population
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Unity Health Toronto

Collaborators

Centre for Addiction and Mental Health

Investigators

  • Principal Investigator: Sakina J Rizvi, PhD, Unity Health Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 22, 2025

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

May 15, 2018

First Submitted That Met QC Criteria

May 15, 2018

First Posted (Actual)

May 25, 2018

Study Record Updates

Last Update Posted (Actual)

September 1, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TPET-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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