Presynaptic Imaging in Major Depressive Episodes After COVID-19

Recruiting

• Conditions: Long COVID; Major Depressive Disorder; Major Depressive Episode
• Interventions: Other: [11C]DTBZ PET scan; Other: [18F]SDM8 PET scan; Other: MRI scan

• Registration Number: NCT06086366
• Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary

The goal of this observational study focuses on understanding and addressing a subset of persistent neuropsychiatric symptoms occurring within 3 months after mild to moderate COVID-19 infection (COVID-DNP). COVID-DNP encompasses major depressive episodes (MDE) with or without additional neuropsychiatric symptoms.

Detailed Description

Participants will undergo two positron emission tomography (PET) scans, one \[11C\]DTBZ scan (for vesicular monoamine transporter 2 (VMAT2) and one \[18F\]SDM8 scan (for synaptic vesicle glycoprotein 2A (SV2A)), as well as one magnetic resonance imaging (MRI) scan.

The main question\[s\] it aims to answer are:

1. The investigators will determine if VMAT2 binding potential (VMAT2 BPND) is reduced in ventral striatum and dorsal putamen in COVID-DNP.

2. The investigators will determine if SV2A total distribution volume (SV2A VT) is reduced in ventral striatum and dorsal putamen in COVID-DNP

Study Timeline

• Study Start: 2023-08-22
• Study First Submitted: 2023-09-05
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-15
• Last Update Submitted: 2023-10-15
• Study First Posted: 2023-10-17
• Last Update Posted: 2023-10-17
• Primary Completion: 2025-09-10
• Study Completion: 2025-09-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• New onset MDE within 3 months after mild or moderate COVID-19, with MDE verified by the research version SCID for DSM 5. See "Positive COVID-19 diagnosis" listed after inclusion/exclusion criteria for a description of how this is determined.
• Age 18 to 75.
• Good general physical health with no active medical conditions based on self-report (except migraine or PASC).

Exclusion Criteria

• Use of antidepressants in the previous month (6 weeks for fluoxetine).
• Use of stimulant medication affecting dopamine release in the previous month
• Use of antipsychotics in the previous month
• History of neurological disease (except migraine, and PASC) based on self-report
• Use of medications or herbal products or natural health products with central nervous system effects in past 2 weeks based on self-report
• Presence of cigarette smoking in the past two months, based on self-report
• Lifetime diagnosis of severe Substance or Alcohol Use Disorder, or diagnosis of mild to moderate Substance or Alcohol Use Disorder in the past two years, based on self-report and verified by the Research Version of Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5-RV)
• Use of recreational drugs, including marijuana, in the past two months, based on self-report and verified by the Research Version of Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5-RV)
• Positive urine drug or cotinine screen at any timepoint during the study
• History of psychotic symptoms secondary to schizophrenia, schizophreniform, bipolar disorder, or brief psychotic disorder prior to COVID-19, based on self-report and verified by the Research Version of Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID-5-RV)
• Currently pregnant, based on self-report or positive pregnancy test at any timepoint during the study, in females (in our PET Centre females up to 65 years of age are given a urine pregnancy test prior to every PET scan)
• Breastfeeding (for females)
• Current disorders of coagulation, blood or ongoing use of anticoagulant medication, based on self-report
• Claustrophobia, based on self-report
• Weight over 400lbs and height over 7ft (requirements for fitting in the scanners and hospital gowns)
• Presence of metal implant, object or electrical devices that are contraindicated for MRI, based on self-report
• Severe allergic reaction to alcohol

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
COVID-DNP	[18F]SDM8 PET scan	Participants that have recovered from mild or moderate COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).
Healthy Control	[11C]DTBZ PET scan	Participants in good physical health, age- and sex-matched to Group 1 and 2 participants.
COVID-DNP	[11C]DTBZ PET scan	Participants that have recovered from mild or moderate COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).
Healthy Control	MRI scan	Participants in good physical health, age- and sex-matched to Group 1 and 2 participants.
COVID-DNP	MRI scan	Participants that have recovered from mild or moderate COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).
Healthy Control	[18F]SDM8 PET scan	Participants in good physical health, age- and sex-matched to Group 1 and 2 participants.

Primary Outcome Measures

Name	Time	Method
Vesicular Monoamine Transporter 2 Binding Potential (VAMT2 BPND)	within 3 to 4 weeks after initiation of screening	The investigators will determine if VMAT2 BPND is changed in ventral striatum and dorsal putamen in COVID-DNP.
Synaptic Vesicle Glycoprotein 2A Total Distribution Volume (SV2A VT)	within 3 to 4 weeks after initiation of screening	The investigators will determine if SV2A VT is changed in ventral striatum and dorsal putamen in COVID-DNP

Trial Locations

Locations (1)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada