Clinical trial NCT04854785: Neuroinflammation in COVID-19 and Depression
Official title: Imaging Neuroinflammation in COVID-19 and Persistent Depression With/Without Other Neuropsychiatric Symptoms
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Major Depressive Episode
Covid19
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2021-04-22
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants that have recovered from mild or moderate COVID-19 respiratory symptoms and have a new onset major depressive episode (MDE).

Brief summary: The purpose of this study is to use state of the art brain imaging technology to investigate neuroinflammation in participants with depression after the respiratory symptoms of coronavirus disease 2019 (COVID-19) have passed.

Detailed description: Participants will undergo two positron emission tomography (PET) scans: one \[18F\]FEPPA scan (for translocator protein (TSPO)) and one \[11C\]SL25.1188 scan (for monoamine oxidase B (MAO-B)) - as well as one magnetic resonance imaging (MRI) scan.

The primary hypotheses are:

1. TSPO total distribution volume (TSPO VT) and MAO-B total distribution volume (MAO-B VT) are greater in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampus in COVID-19 with new onset, persistent major depressive episode (MDE) with or without other neuropsychiatric symptoms after recovery from mild respiratory symptoms (DNP-mild).
2. TSPO VT and MAO-B VT are greater in the PFC, ACC, and hippocampus in COVID-19 with new onset, persistent MDE with or without other persistent neuropsychiatric symptoms after recovery from moderate respiratory symptoms (DNP-moderate).

Exploratory hypotheses are:

1. Greater TSPO VT and MAO-B VT in the PFC, ACC, and hippocampus will be positively associated with severity of MDE symptoms and poorer performance on cognitive tasks.
2. TSPO VT and MAO-B VT will be positively correlated in the PFC, ACC and hippocampus in COVID-DNP.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 80
* Diagnosis of COVID-19
* Recovered from mild or moderate COVID-19 symptoms. Mild is defined as no evidence of pneumonia or hypoxia. Moderate is defined as presence of clinical symptoms of pneumonia but not severe enough to require ongoing use of supplementary oxygen.
* Recovered from physical COVID-19 symptoms including cough, shortness of breath, fever, chills, or gastrointestinal upset for at least 4 weeks
* New onset major depressive episode (MDE) within 3 months after COVID-19, as verified by the Research Version of Structured Clinical Interview for DSM 5 (SCID-5-RV)
* High-affinity-binder (HAB) or mixed-affinity-binder (MAB) genotype for rs6971 polymorphism, based on saliva genetic testing

Exclusion Criteria:

* Lifetime history of an autoimmune disease
* Lifetime history of a neurological disease, excluding migraine
* Lifetime diagnosis of Antisocial or Borderline Personality disorder
* Lifetime history of psychotic symptoms prior to COVID-19
* Lifetime diagnosis of Substance of Alcohol Use Disorder
* Use of street drugs, including marijuana, in the past two months
* Presence of cigarette smoking in the past two months
* Positive urine drug or cotinine screen at any timepoint during the study
* Currently pregnant
* Currently breastfeeding
* Use of aspirin or ibuprofen within the past 2 weeks
* Use of any other anti-inflammatory medication or MAO-B inhibitors within the past 4 weeks
* Use of herbal remedies in the past month
* Presence of metal implant, object or electrical devices that are contraindicated for MRI
* Current disorders of coagulation, blood or ongoing use of anticoagulant medication
* Claustrophobia
* Weight over 400lbs and height over 7ft
* History of undergoing a number of PET scans that will lead participants to exceed the annual (20mSv) / lifetime (8 PET scans) radiation by completing this study
* Current participation in another research study

Primary outcomes:
measure: Translocator protein total distribution volume in prefrontal cortex, anterior cingulate cortex, and hippocampus
timeFrame: within 3 to 4 weeks after initiation of screening
measure: Monoamine oxidase B total distribution volume in prefrontal cortex, anterior cingulate cortex, and hippocampus
timeFrame: within 3 to 4 weeks after initiation of screening
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Brain Health Imaging Centre, Centre for Addiction and Mental Health (CAMH)
name: Jeffrey H Meyer, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References: