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

Phase 2

• Conditions: COVID-19
• Interventions: Radiation: [18F]DPA-714 positron emission tomography (PET) scan

• Registration Number: NCT05371522
• Lead Sponsor: Amsterdam UMC, location VUmc

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.

Detailed Description

In this study we will include 20 post-COVID-19 patients (\>3 months after diagnosis or discharge from hospital) (50% with post-infectious fatigue and/or cognitive complaints) and 50% without post-infectious fatigue/cognitive complaints; matched for disease severity). We will also include 10 age/sex-matched healthy controls without history of COVID-19 or severe fatigue/cognitive complaints. RS6971 polymorphism of the TSPO receptor will be determined and low affinity binders will be excluded from this study.

The main study parameter is the measurement of in vivo neuroinflammation with a \[18F\]DPA-714 90 minutes PET scan, alternately capturing brain (60 minutes) and body (30 minutes) with both continuous on-line and manual arterial blood sampling for full quantification (\[18F\]DPA-714 volume of distribution). The 30-minutes body scan will be performed to examine whole-body inflammation. Brain MRI will be performed for functional and anatomical information. We will use questionnaires and neuropsychological evaluation to assess chronic fatigue, depressive, anxiety and cognitive symptoms, partially for descriptive purposes.

Study Timeline

• Study Start: 2022-02-03
• Status Verified: 2022-05
• Study First Submitted: 2022-05-11
• Study First Submitted QC: 2022-05-11
• Last Update Submitted: 2022-05-11
• Study First Posted: 2022-05-12
• Last Update Posted: 2022-05-12
• Primary Completion: 2023-09
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

VU University Medical Center; 🇳🇱 Amsterdam, Netherlands