68Ga-FAPI PET/CT to Detect Ongoing Fibroblast Activity in Post-acute COVID-19

Pulmonary Fibrosis Clinical Trial

— FAPI CLIMATE  

Official title:

68Ga-FAPI PET/CT to Detect Ongoing Fibroblast Activity in Post-acute COVID-19 With Respiratory Impairment After Hospital Discharge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05981885
• Other study ID #: 202100802
• Status: Completed
• Start date: June 9, 2022
• Est. completion date: May 17, 2024

Study information

• Verified date: May 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of this observational study is to investigate the role fibroblasts play in the persistent respiratory complaints after a COVID-19 infection. Fibroblasts are involved in tissue remodeling and repair by creating scar-tissue (fibrosis) after tissue damage has occurred. The hypothesis is that this process of fibrosis is ongoing in patients with persistent complaints. To evaluate the roll of fibroblasts a new type of scan is used that is capable of imaging active fibroblasts, a 68Ga-FAPI PET/CT scan.

Description:

Rationale: The pathogenesis of post-acute COVID-19 with respiratory complaints remains unknown. We aim to explore the pulmonary pattern and fibrosis activity in patients with post-acute COVID-19 with respiratory complaints using 68Ga-FAPI Positron Emission Tomography-Computed Tomography (PET/CT) imaging.

Objective: To relate pulmonary fibroblast activity, measured by FAPI-PET/CT at least 3 months after hospital discharge, to interstitial lung abnormalities on high resolution CT (HRCT) at the same time point in post-acute COVID-19 patients with respiratory complaints.

Study design: This is a ZonMw funded single center prospective observational cohort study of post-acute COVID-19 patients with respiratory complaints.

Study population: We will recruit 20 adult patients, all post-ICU or post High-Flow Nasal Oxygen therapy due to there COVID-19 infection, with post-acute COVID-19 and respiratory complaints that will undergo 68Ga-FAPI PET/CT imaging to establish pulmonary fibrosis activity.

Main study parameters/endpoints: To assess the degree of Fibroblast Activation Protein expression on 68Ga-FAPI PET/CT at least 3 months after hospital discharge and to relate this to interstitial lung abnormalities on HRCT at the same time point.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 17, 2024
• Est. primary completion date: November 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male patients >18 years and female patients >20 years discharged from hospital after PCR-confirmed COVID-19 infection.

• Previous ICU or ward admission with high flow nasal oxygen (HFNO) or mechanical ventilation.

• Persistent respiratory complaints (shortness of breath) at least 3 months after hospital discharge.

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.

• Severe or significant comorbidity, defined as COPD GOLD stage II or higher and/or known interstitial lung disease.

• Women who are pregnant or breastfeeding.

Related Conditions & MeSH terms

• COVID-19
• Pulmonary Fibrosis

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary SUV values	Based on the FAPI PET/CT scan 3-dimensinal volumes of intrest (VOI) are drawn of high FAPI uptake areas (leasions) and non-uptake areas. Using these VOIs SUV values and metabolic active volume (MAV) can be calculated which then can be used to calculate: total lesion FAPI (TL-FAPI), whole-lung FAPI-MAV (wl FAPI-MAV), wlSUVmean and whole lung TL-FAPI (wlTL-FAPI).	At time of inclusion (T0)
Secondary	Correlate biomarkers to pulmonary SUV values	A correlation between the pulmonary FAPI uptake, reported as SUV values (see outcome 1) will be correlated with fibrosis and inflammatory specific biomarkers using Pearson's or Spearman's test.	At time of inclusion (T0)
Secondary	6 minute walking test vs pulmonary SUV values	The total walked distance in meters during 6 minutes is correlated with pulmonary FAPI uptake, reported as SUV values (see outcome 1) using Pearson's or Spearman's test.	At time of inclusion (T0)
Secondary	DCLO and VC vs pulmonary SUV values	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with DCLO and VC using Pearon's or Spearman's test.	At time of inclusion (T0)
Secondary	Daily impairments (EQ-5D questionnaire) vs pulmonary SUV values	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.	At time of inclusion (T0)
Secondary	Cellular phenotypes	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to systemic and upper respiratory tract cellular phenotypes determined by single cell RNA sequencing using Pearon's or Spearmen's test.	At time of inclusion (T0)
Secondary	HRCT	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).	At time of inclusion (T0)
Secondary	Follow-up HRCT	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings in case of persistent respiratory complaints 8-10 months after T0. Findings that are correlated are: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).	10 months after T0
Secondary	Follow-up daily impairments (EQ-5D questionnaire) vs pulmonary SUV values	Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.	10 months after T0