Recruiting

TRD Neurobiology

Sponsor:

Unity Health Toronto

Code:

NCT03537794

Conditions

Treatment Resistant Depression

Depression - Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 25 - 65

Healthy Volunteers: Accepted

Interventions

PET scans

Study Details

Brief 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. 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.

Conditions

Treatment Resistant Depression

Depression - Major Depressive Disorder

Study ID

NCT03537794

Start date

Aug 22, 2025

Status verified date

Feb, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 25 - 65

Healthy Volunteers: Accepted

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 Design

Enrollment

45 participants

Anticipated

Interventions and Outcome Measures

Arms

Treatment Resistant Depression

Unmedicated Individuals with Treatment Resistant Depression

Major Depressive Disorder

Unmedicated Individuals with Major Depressive Disorder

Healthy Control

healthy controls with no previous psychiatric disorders

Interventions

PET scans

PET scans and PHNO scans

Primary outcome measure

  • Synaptic Density [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

Sakina J Rizvi, PhD

416-864-6060rizvis@smh.ca

Ariel Graff-Guerrero, MD, PhD

416-535-850ariel.graff@camh.ca

Locations

Unity Health Toronto

Recruiting

Toronto, Ontario, Canada, M5B 1M4

Contacts

Hailey A Wright, H.B.Arts Sc.

416-360-4000hailey.wright@unityhealth.to

Leen Ghanayem, MSc

416-360-4000Leen.Ghanayem@unityhealth.to

Principal Investigator:

Sakina J Rizvi, PhD

More Information

Sponsor

Unity Health Toronto

Last update posted

Sep 1, 2026

Last verified

Feb, 2026

Keywords

  • depression
  • synaptic density
  • trd
  • mdd
  • treatment resistant
  • brain imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Unity Health Toronto on 2026-09-01.