Clinical trial NCT06911476: From Inflammation to Remodelling Towards Personalized Diagnosis in Post-acute Sequelae of COVID-19
Official title: From Inflammation Biomarkers to Remoddeling (FAPI PET/CT) Towards Personalized Diagnosis in Post-acute Sequelae of COVID-19
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: PASC Post Acute Sequelae of COVID 19
Long COVID
Long Covid-19
PASC
FAPI
FAP
Fibroblast Activation Protein Inhibitor
Fibroblast
Restrictive Lung Disease
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2025-04-04
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited from the P4O2 COVID-19 cohort (The Netherlands - www.p4o2.org). If too few patients from the P4O2 cohort are willing or eligible to participate in the LIBERATE study, 'healthy' controls from other cohorts may be included as a third control group to meet the required number of participants.

Brief summary: Rationale: The diagnosis and pathogenesis of long COVID remains unknown. We have previously shown that \[68Ga\]FAPI Positron Emission Tomography-Computed Tomography (PET/CT) imaging shows potential for diagnosis and molecular understanding of this syndrome. We have previously shown that fibroblast activation protein (FAP) can be imaged in the lung, muscle and nasopharynx of long COVID patients (with dyspnea and fatigue). However, these preliminary data are derived from a selective group of patients with long COVID after critical COVID-19. We aim to explore the generalizability of these findings in patients with long COVID with dyspnea and fatigue, irrespective of the severity of their acute SARS-CoV-2 infection.

Primary objective: To assess if pulmonary fibroblast activity, measured by \[68Ga\]FAPI-46 PET/CT, is higher in patients with current long COVID dyspnea and fatigue compared to patients with resolved complaints.

Study design: This is a ZonMw funded single centre prospective observational cohort study of long COVID-19 patients with dyspnea and fatigue.

Study population: We will recruit 60 adult long COVID patients (aged \>20 years) of which 30 have complaints of dyspnea and fatigue and compare them to 30 patients with resolved complaints and healthy controls.

Main study parameters/endpoints: The primary endpoint is FAP expression in the lung measured by \[68Ga\]FAPI-46 PET/CT. Secondary endpoints are the expression of FAP in other tissues (muscle) and the relation between FAP and inflammation and remodelling biomarkers in various biological samples (e.g. serum/nasal epithelium).

Study procedures: In a single visit day the following data and samples will be collected: questionnaires, a lung function test, 6-minute walking test, blood samples, nose swabs, \[68Ga\]FAPI PET/CT scan and HRCT scan. When increased \[68Ga\]FAPI uptake is measured in the muscles a muscle biopsy will be performed as well.


Eligibility criteria: Inclusion Criteria:

- Self-reported complaints of dyspnea or fatigue \> 3 months after SARS-CoV-2 infection confirmed with PCR, serology test or COVID-19 Reporting and Data System (CO-RADS) score 4/5.

Exclusion Criteria:

* Inability or unwilling to give informed consent.
* History of claustrophobia or feeling of inability to tolerate supine position for the PET/CT scans.
* Individuals who are pregnant or currently breastfeeding are not eligible to participate

Primary outcomes:
measure: Pulmonary FAP expression
timeFrame: Day 1
Secondary outcomes:
measure: Whole body FAP expression
timeFrame: Day 1
measure: Pulmonary FAP expression vs clinical endpoints
timeFrame: Day 1
measure: Whole body FAP expression vs clinical endpoints
timeFrame: Day 1
measure: Serum biomarkers
timeFrame: Day 1
Other outcomes:
measure: HRCT vs pulmonary FAP expression
timeFrame: Day 1
measure: Muscle biopsies
timeFrame: Day 1
Locations:
Study officials:
affiliation: Department of Intensive Care, University Medical Center Groningen
name: J Pillay, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: