- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05433324
"Long COVID-19" on the Human Brain
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Philip Gerretsen, MD, PhD
- Phone Number: 39426 416-535-8501
- Email: philip.gerretsen@camh.ca
Study Contact Backup
- Name: Ariel Graff, MD, PhD
- Phone Number: 34834 416-535-8501
- Email: ariel.graff@camh.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5T1R8
- Recruiting
- Centre for Addiction and Mental Health
-
Contact:
- Philip Gerretsen, MD, PhD
- Phone Number: 39426 416-535-8501
- Email: philip.gerretsen@camh.ca
-
Contact:
- Ariel Graff, MD, PhD
- Phone Number: 34834 416-535-8501
- Email: ariel.graff@camh.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
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.
- 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.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Group A
Persons previously infected with COVID-19 experiencing CNS-PASC within 6 months of recovery
|
All groups will undergo cognitive tests and brain imaging scans (MRI & PET)
|
Group B
Persons previously infected with COVID-19 without CNS-PASC symptoms within 6 months of recovery
|
All groups will undergo cognitive tests and brain imaging scans (MRI & PET)
|
Group C
A control group of persons not previously infected with COVID-19.
|
All groups will undergo cognitive tests and brain imaging scans (MRI & PET)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
At screening, baseline and at 3-month follow-up
|
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.
|
At baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Quality of Life
Time Frame: At baseline and at 3-month follow-up
|
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.
|
At baseline and at 3-month follow-up
|
Cognitive, Emotional, Motor and Sensation Measures
Time Frame: At baseline and at 3-month follow-up
|
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.
|
At baseline and at 3-month follow-up
|
Biomarker Measures
Time Frame: At screening, baseline and at 3-month follow-up
|
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
|
At screening, baseline and at 3-month follow-up
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Ariel Graff, MD, PhD, Centre for Addiction and Mental Health
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 139/2021
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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