COVID-19NCT05433324
"Long COVID-19" on the Human Brain
An observational study of COVID-19 and Long Covid, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Over one million Canadians have been infected by COVID-19. Many people who have been infected by COVID-19 experience negative mental symptoms, such as "brain fog" and fatigue. For many of these people, they continue to feel these negative mental symptoms even after recovering from COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19, Long Covid, Post Acute Sequelae of COVID-19
- What is being tested?
- MRI and PET Scans
- How many people
- 48 participants
- Where
- 1 siteCanada
- Study dates
- 5 Aug 2022to 5 Nov 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Individuals with or without prior infection with COVID-19
Who may be able to join
- Persons of all races, ethnicities, genders, and sex.
- 18 years of age or older.
- Fully vaccinated for COVID-19 with authorized vaccines in Canada.
- Participants in COVID-19 groups (Group A and B) will have the following additional inclusion criteria:
- Previously infected with mild-moderate COVID-19 (i.e., out-patients never hospitalized for COVID-19), as confirmed by review of clinical history.
- Not currently infected with SARS-COV-2, as confirmed by COVID-19 Rapid Antigen Test (RAT).
- Additionally, participants enrolled as part of the CNS-PASC group (Group A), must also:
- 1. Currently experience CNS-PASC symptoms, not present prior to infection, as confirmed by the "Long COVID-19 Symptom Assessment" scale.
Who cannot join
- Participants will be excluded if they meet ANY of the criteria listed below:
- Unstable medical conditions and/or active uncontrolled autoimmune or inflammatory conditions.
- Neurological conditions and/or concussion present prior to COVID-19 infection.
- Substance abuse disorder (except caffeine, nicotine, and cannabis/marijuana) within 6 months of entering the study, as determined by the Structured Clinical Interview (37)
- Positive urine drug screen for drugs of abuse at the screening visit (except for cannabis/marijuana).
- Pregnancy (Note: Females up to age 65 must have negative urine pregnancy test at screening), or breastfeeding.
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- Score <32 on the Wide Range Achievement Test-III.
- Receiving treatment with medications such as levetiracetam that blocks SV2a binding.
- Pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan.
- Body size/weight above the limits for PET and MRI scanners.
- Exceeding allowed annual radiation exposure levels for research scans of 20 mSv in the past 12 months as outlined by our PET Centre guidelines.
- Having completed multiple PET scans in the past, such that participation in this study would cause participant to exceed lifetime limit (8 PET scans).
- Currently receiving active treatment for cancer.
- Claustrophobia.
Trial locations and contacts
1 site in 1 country.
About this study
Over one million Canadians have been infected by COVID-19. Many people who have been infected by COVID-19 experience negative mental symptoms, such as "brain fog" and fatigue. For many of these people, they continue to feel these negative mental symptoms even after recovering from COVID-19. However, scientists still do not know how COVID-19 harms the human brain and causes these mental problems. Our goal is to use advanced brain imaging to determine whether people who have been infected with COVID-19 show damage in their brain. We hope that this information will help doctors determine what treatments should be provided to help people who are suffering from continuing mental problems after being infected with COVID-19.
Read the detailed description
This is a cross-sectional study composed of three participant groups. 1) persons previously infected with COVID-19 experiencing CNS-PASC (central nervous system Post-Acute Sequelae of COVID-19) within 6 months of recovery, 2) persons previously infected with COVID-19 without CNS-PASC symptoms within 6 months of recovery, and 3) a control group of persons not previously infected with COVID-19. Groups will be as similar as possible for age and substance use. This study will examine synaptic vesicular density (henceforth, synaptic density), as measured with positron emission tomography (PET), and neuroinflammation markers, as measured with Magnetic resonance imaging (MRI), as well as clinical, cognitive, and peripheral biomarkers between the groups.
Participants that meet the inclusion and exclusion criteria at the initial screening visit (Visit 1) and provide written consent will be enrolled into the study. Participants will undergo PET scans with the novel PET tracer [18F]SDM-8 to quantify synaptic density levels. MRI scans will be collected, and clinical assessments will be completed at the same time. Each participant will participate in four study visits at defined time points over the course of their enrolment, including the initial participant screening visit (Visit 1). Brain imaging scans and PASC/cognitive assessments will occur at visits 2 and 3, followed by a subsequent PASC/cognitive assessment follow-up at visit 4, occurring 2-3 months after Visit 3.
- Conditions
- COVID-19, Long Covid, Post Acute Sequelae of COVID-19
- Being tested
- MRI and PET Scans
- Keywords
- Magnetic resonance imaging, Positron emission tomography
- Medical subject headings
- COVID-19, Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI and PET ScansOther
All groups will undergo cognitive tests and brain imaging scans (MRI \& PET)
| Study group | Role | What they receive |
|---|---|---|
| Group A | Persons previously infected with COVID-19 experiencing CNS-PASC within 6 months of recovery Receives: Other: MRI and PET Scans | |
| Group B | Persons previously infected with COVID-19 without CNS-PASC symptoms within 6 months of recovery Receives: Other: MRI and PET Scans | |
| Group C | A control group of persons not previously infected with COVID-19. Receives: Other: MRI and PET Scans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Synaptic Density (PET Scan)
[18F]SDM-8's regional binding potential non-displaceable (BPND) will be calculated using the simplified reference tissue model (SRTM) (31) using as reference the centrum semiovale (32). The PET data will be analyzed using both a priori regions of interest and exploratory whole-brain voxel-based analysis method.
Measured: At baseline
Presence and Severity of CNS and PASC Symptoms
A Likert-type scale of the most common COVID-19 sequela symptoms will be employed. The "Long COVID-19 Symptom Assessment" self-report consists of 46 common COVID-19 sequela symptoms, both neurological and non-neurological.
Measured: At screening, baseline and at 3-month follow-up
Secondary outcomes (3)
Changes in Quality of Life
The World Health Organization Disability Assessment Schedule (WHODAS 2.0) will be administrated. The WHODAS 2.0 is a short, easily administered test that takes approximately 5-20 minutes to complete. It covers 6 domains of function to assess a person's quality of life which include cognition, mobility, self-care, getting along, life activities and participation.
Measured: At baseline and at 3-month follow-up
Cognitive, Emotional, Motor and Sensation Measures
Assessment of neurological and behavioural function will be done using the National Institute of Health (NIH) Toolbox (www.nihtoolbox.org). The measures in the toolbox are administered in two hours and have been validated for the assessment of longitudinal epidemiologic outcomes.
Measured: At baseline and at 3-month follow-up
Biomarker Measures
COVID-19 Humoral Status, CNS Humoral Autoreactivities in Tissue Microarrays, Biobanking of Live PBMC, COVID-19-specific T Cell Cytokine Response, Mucosal immune response, Metabolic Markers
Measured: At screening, baseline and at 3-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2022
- Study start5 Aug 2022
- Primary completion5 Nov 2024
- Study completion5 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies 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
- Prospective
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre
- Responsible party
- Sponsor
- Investigators
- Ariel Graff, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05433324
- Sponsor's protocol ID
- 139/2021
- Status last verified
- Mar 2025
- First submitted
- 23 Jun 2022
- Last updated
- 28 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Long COVID-19" on the Human Brain
- ClinicalTrials.gov ID
- NCT05433324
- Acronym / sponsor ID
- 139/2021
- Conditions
- COVID-19, Long Covid, Post Acute Sequelae of COVID-19
- Keywords
- Magnetic resonance imaging, Positron emission tomography
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre
- Study start
- 5 Aug 2022 (actual)
- Primary completion
- 5 Nov 2024 (actual)
- Study completion
- 5 Nov 2024 (actual)
- First posted
- 27 Jun 2022 (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.
Over one million Canadians have been infected by COVID-19. Many people who have been infected by COVID-19 experience negative mental symptoms, such as "brain fog" and fatigue. For many of these people, they continue to feel these negative mental symptoms even after recovering from COVID-19. However, scientists still do not know how COVID-19 harms the human brain and causes these mental problems. Our goal is to use advanced brain imaging to determine whether people who have been infected with COVID-19 show damage in their brain. We hope that this information will help doctors determine what treatments should be provided to help people who are suffering from continuing mental problems after being infected with COVID-19.
Detailed description
This is a cross-sectional study composed of three participant groups. 1) persons previously infected with COVID-19 experiencing CNS-PASC (central nervous system Post-Acute Sequelae of COVID-19) within 6 months of recovery, 2) persons previously infected with COVID-19 without CNS-PASC symptoms within 6 months of recovery, and 3) a control group of persons not previously infected with COVID-19. Groups will be as similar as possible for age and substance use. This study will examine synaptic vesicular density (henceforth, synaptic density), as measured with positron emission tomography (PET), and neuroinflammation markers, as measured with Magnetic resonance imaging (MRI), as well as clinical, cognitive, and peripheral biomarkers between the groups.
Participants that meet the inclusion and exclusion criteria at the initial screening visit (Visit 1) and provide written consent will be enrolled into the study. Participants will undergo PET scans with the novel PET tracer [18F]SDM-8 to quantify synaptic density levels. MRI scans will be collected, and clinical assessments will be completed at the same time. Each participant will participate in four study visits at defined time points over the course of their enrolment, including the initial participant screening visit (Visit 1). Brain imaging scans and PASC/cognitive assessments will occur at visits 2 and 3, followed by a subsequent PASC/cognitive assessment follow-up at visit 4, occurring 2-3 months after Visit 3.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Other: MRI and PET ScansPersons previously infected with COVID-19 experiencing CNS-PASC within 6 months of recovery |
| Group B | – | Other: MRI and PET ScansPersons previously infected with COVID-19 without CNS-PASC symptoms within 6 months of recovery |
| Group C | – | Other: MRI and PET ScansA control group of persons not previously infected with COVID-19. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with or without prior infection with COVID-19
Key inclusion criteria (8 listed)
- Persons of all races, ethnicities, genders, and sex.
- 18 years of age or older.
- Fully vaccinated for COVID-19 with authorized vaccines in Canada.
- Participants in COVID-19 groups (Group A and B) will have the following additional inclusion criteria:
- Previously infected with mild-moderate COVID-19 (i.e., out-patients never hospitalized for COVID-19), as confirmed by review of clinical history.
Key exclusion criteria (14 listed)
- Unstable medical conditions and/or active uncontrolled autoimmune or inflammatory conditions.
- Neurological conditions and/or concussion present prior to COVID-19 infection.
- Substance abuse disorder (except caffeine, nicotine, and cannabis/marijuana) within 6 months of entering the study, as determined by the Structured Clinical Interview (37)
- Positive urine drug screen for drugs of abuse at the screening visit (except for cannabis/marijuana).
- Pregnancy (Note: Females up to age 65 must have negative urine pregnancy test at screening), or breastfeeding.
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 |
|---|---|---|
| MRI and PET ScansAll groups will undergo cognitive tests and brain imaging scans (MRI \& PET) | Other | Group A, Group B, Group C |
Primary outcome
Synaptic Density (PET Scan)
Time frame: At baseline
[18F]SDM-8's regional binding potential non-displaceable (BPND) will be calculated using the simplified reference tissue model (SRTM) (31) using as reference the centrum semiovale (32). The PET data will be analyzed using both a priori regions of interest and exploratory whole-brain voxel-based analysis method.
Presence and Severity of CNS and PASC Symptoms
Time frame: At screening, baseline and at 3-month follow-up
A Likert-type scale of the most common COVID-19 sequela symptoms will be employed. The "Long COVID-19 Symptom Assessment" self-report consists of 46 common COVID-19 sequela symptoms, both neurological and non-neurological.
3 secondary outcomes
Changes in Quality of Life
Time frame: At baseline and at 3-month follow-up
Cognitive, Emotional, Motor and Sensation Measures
Time frame: At baseline and at 3-month follow-up
Biomarker Measures
Time frame: At screening, baseline and at 3-month follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Ariel Graff, MD, PhD principal investigator
Centre for Addiction and Mental Health
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 COVID-19 and Long Covid, run by Centre for Addiction and Mental Health 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 14 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: finished, as of the sponsor's last update on 28 Mar 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Synaptic Density (PET Scan) (time frame: At baseline). The study lists 2 primary outcomes in all. 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 28 Mar 2025.