Treatment Resistant DepressionTPETNCT03537794
Characterizing Synaptic Density in Treatment Resistant Depression
An observational study of Treatment Resistant Depression and Depression - Major Depressive Disorder, run by Unity Health Toronto at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Treatment Resistant Depression, Depression - Major Depressive Disorder
- What is being tested?
- PET scans
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- 22 Aug 2025to Dec 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
- Ages between 25 and 65 years
- Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)
Who cannot join
- 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.
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- Pregnancy/lactation
- Medical condition requiring immediate investigation or treatment
- Lifetime history of any psychiatric disorder
- Lifetime history of receiving an antidepressant
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Unity Health Toronto
Toronto, Ontario, M5B 1M4
Hailey A Wright, H.B.Arts Sc., 416-360-4000 ext. 7844, hailey.wright@unityhealth.to
Leen Ghanayem, MSc, 416-360-4000 ext. 7844, Leen.Ghanayem@unityhealth.to
About this study
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. The investigators are particularly interested in synaptic density, which helps to understand how different parts of the brain communicate with one another. 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, investigators 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.
Read the 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, the investigators will collect detailed information about participants 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 used is called [18F]- SynVesT-1, which measures synaptic density. In addition, the MRI scan will be used to examine 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 the brain and how it relates to brain function during memory and reward learning tasks. This information will be important for advancing knowledge of the brain biology of TRD and potential new areas for treatment development.
- Being tested
- PET scans
- Keywords
- depression, synaptic density, trd, mdd, treatment resistant, brain imaging
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET scansDiagnostic test
PET scans and PHNO scans
| Study group | Role | What they receive |
|---|---|---|
| Treatment Resistant Depression | Unmedicated Individuals with Treatment Resistant Depression Receives: Diagnostic Test: PET scans | |
| Major Depressive Disorder | Unmedicated Individuals with Major Depressive Disorder Receives: Diagnostic Test: PET scans | |
| Healthy Control | healthy controls with no previous psychiatric disorders Receives: Diagnostic Test: PET scans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Synaptic Density
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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start22 Aug 2025
- Primary completionDec 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for Addiction and Mental Health
- Responsible party
- Sponsor
- Investigators
- Sakina J Rizvi, PhD, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537794
- Sponsor's protocol ID
- TPET-01
- Acronym
- TPET
- Status last verified
- Feb 2026
- First submitted
- 15 May 2018
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing Synaptic Density in Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT03537794
- Acronym / sponsor ID
- TPET / TPET-01
- Keywords
- depression, synaptic density, trd, mdd, treatment resistant, brain imaging
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Centre for Addiction and Mental Health
- Study start
- 22 Aug 2025 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 25 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. The investigators are particularly interested in synaptic density, which helps to understand how different parts of the brain communicate with one another. 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, investigators 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.
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, the investigators will collect detailed information about participants 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 used is called [18F]- SynVesT-1, which measures synaptic density. In addition, the MRI scan will be used to examine 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 the brain and how it relates to brain function during memory and reward learning tasks. This information will be important for advancing knowledge of the brain biology of TRD and potential new areas for treatment development.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment Resistant Depression | – | Diagnostic Test: PET scansUnmedicated Individuals with Treatment Resistant Depression |
| Major Depressive Disorder | – | Diagnostic Test: PET scansUnmedicated Individuals with Major Depressive Disorder |
| Healthy Control | – | Diagnostic Test: PET scanshealthy controls with no previous psychiatric disorders |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- Ages between 25 and 65 years
- Ability to undergo MRI scanning (absence of metal, pacemakers, etc.)
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| PET scansPET scans and PHNO scans | Diagnostic test | Healthy Control, Major Depressive Disorder, Treatment Resistant Depression |
Primary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: Undecided
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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.
Sakina J Rizvi, PhD principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Treatment Resistant Depression and Depression - Major Depressive Disorder, run by Unity Health Toronto at 1 site in Canada.
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 8 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 15 Sep 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 Canada. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sakina J Rizvi, PhD (416-864-6060 ext. 6489, rizvis@smh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Synaptic Density (time frame: 3 years). 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 15 Sep 2026.