Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19

NCT05371522 | Unknown Phase 2

• 2 other identifiers: 2021.03332021-000781-15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroinflammation can be an important regulator of long COVID, specifically fatigue and cognitive complaints. There is evidence that peripheral inflammation and neuro-inflammation are involved in fatigue and cognitive complaints, but precise pathophysiological mechanisms and causal relationship with viral infections are still unknown. The primary aim of this study is to quantify neuroinflammation with \[18F\]DPA-714 (TSPO-binding) PET scans in post-COVID-19 patients with and without post-infectious fatigue and cognitive complaints and relate it to cognitive, psychiatric and post-infectious fatigue symptoms.

Conditions

COVID-19

Keywords

long COVID, imaging, (neuro)inflammation

Outcome Measures

Primary Outcomes (2)

• Quantitative neuroinflammation as measured with [18F]DPA-714 positron emission tomography (PET)

  60 minute dynamic brain scan

• Whole-body inflammation as measured with [18F]DPA-714 positron emission

  30 minute static whole-body scan

Study Arms (1)

[18F]DPA-714

EXPERIMENTAL

All individuals included will undergo a \[18F\]DPA-714 positron emission tomography (PET) scan, irrespective of the existence of post-COVID-19 complaints.

Radiation: [18F]DPA-714 positron emission tomography (PET) scan

Interventions

[18F]DPA-714 positron emission tomography (PET) scan RADIATION

60 minute dynamic brain \[18F\]DPA-714 positron emission tomography (PET) scan followed by a 30 minute static whole body positron emission tomography (PET) scan

[18F]DPA-714

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The individual was diagnosed with symptomatic COVID-19, confirmed by a positive PCR for SARS-CoV-2, positive SARS-CoV-2 serology or CO-RADS (COVID-19 Reporting and Data System) 4 or 5 on CT-scan, or antigen quicktest, or had typical symptoms and was part of a household in which another person was tested positive by PCR 2 weeks before or after the first day of illness;
• The individual is 3 months after being diagnosed with COVID-19 or after hospital discharge in case the patient was admitted.
• The individual is in the range 40-60 years of age (to ensure radiation safety)
• The individual has sufficient command of the Dutch language
• Genotyping of rs6971 must show that the individual is a mixed or high affinity binder
• The patient experiences severe levels of fatigue (≥ 40) on the fatigue subscale of the Checklist Individual Strength \[CIS-fatigue\]) and/or cognitive complaints (≥ 15) on the concentration subscale of the Checklist Individual Strength \[CIS-concentration\].The severe fatigue or cognitive complaints started with or increased substantially directly after the onset of symptoms of COVID-19;
• The patient reports physical/social disability (≤ 65 on the Rand36 physical functioning subscale or a score of ≥ 10 on the Work and Social Adjustment Scale \[WSAS\];
• The individual experiences no significant levels of fatigue (\< 35 on the fatigue subscale of the Checklist Individual Strength \[CIS-fatigue\]) or cognitive complaints (\<15 on the concentration subscale of the Checklist Individual Strength \[CIS-concentration\]) and does not subjectively major symptoms of fatigue or cognitive complaints. Based upon average of normal population +1SD.
• The individual reports no physical/social disability (\> 65 on the Rand36 physical functioning subscale or a score of \< 10 on the Work and Social Adjustment Scale \[WSAS\]
• Should be negatively tested for COVID-19 trough PCR, serology, antibodies, or via antigen quicktest
• No evidence for substantial fatigue or cognitive complaints as evidenced by the CIS subscale fatigue (\<35) and CIS subscale concentration (\<15) and does not subjectively major symptoms of fatigue or cognitive complaints. Based upon average of normal population +1SD
• The individual is in the range 40-60 years of age (to ensure radiation safety)
• The individual has sufficient command of the Dutch language
• Genotyping of rs6971 must show that the individual is a mixed or high affinity binder

You may not qualify if:

• Rs6971 shows low affinity binding
• Individuals who are unable to lay still for scanning due to claustrophobia or severe back pain or trypanophobia (fear of needles)
• Gross neurological pathology (strategic or lobar infarcts or stroke or neurotrauma) on MRI or CT that may interfere with the interpretation of the PET scan.
• Have a hemoglobin test (Hb) result of \< to 8 in males and \< to 7 in females;
• Are females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception. Females of childbearing potential must not be pregnant (negative serum β-HCG at the time of screening and negative urine β-HCG within 24 hours prior to injection) or breastfeeding at screening.
• Have donated blood within 6 months prior to the \[18F\]DPA-714 PET scan day;
• The individual has an already known psychiatric or somatic condition that can explain his/her fatigue or major psychiatric disorder other than somatic-symptom disorder (chronic fatigue) as a main diagnosis. We will also screen for the presence of Post-Traumatic Stress Disorder PTSD as a main diagnosis\] (PCL-5) which prevalence may be high in this patient group because of traumatic experiences during the acute phase of COVID-19. We will also screen for the presence of depressive disorder as a main diagnosis. To screen for PTSD and depressive disorder we will use the Diagnostic and Statistical Manual of Mental Disorders version 5 and verbally check if (any) symptoms do not meet the requirements for a PTSS or depression diagnostic/classification;
• Current use of benzodiazepines11brg

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

COVID-19; Post-Acute COVID-19 Syndrome

Interventions

2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bart NM van Berckel, Prof.

  Radiology & Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Molecular Brain Imaging

Model Details: All individuals included will undergo a \[18F\]DPA-714 positron emission tomography (PET) scan

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 12, 2022
• Study Start: February 3, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: May 12, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)