Effects of COVID-19 Infection and Critical Illness on Diaphragm Tissue Characteristics and Movement, Visualized With MRI

Covid19 Clinical Trial

Official title:

Effects of COVID-19-infection and Mechanical Ventilation on Movement and Tissue Characteristics of the Diaphragm, Visualized by Magnetic Resonance Imaging: a Proof-of-concept Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04735757
• Other study ID #: NL 72271.029.19
• Status: Recruiting
• Start date: February 3, 2021
• Est. completion date: January 19, 2023

Study information

• Verified date: March 2021
• Source: VU University Medical Center
• Contact: Leo Heunks, Prof. Dr.
• Phone: (020) 444 4444
• Email: l.heunks[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

COVID-19-infection has a large impact on the respiratory system and possibly on the diaphragm, the main respiratory muscle. In ICU-patients, diaphragm weakness is associated with prolonged ICU-stay, difficult weaning and increased mortality. Our research group recently found evidence for fibrosis and expression of genes involved in fibrosis as well as viral infiltration of the SARS-CoV-2 virus in diaphragm biopsies from COVID-19 ICU patients. This finding suggests a unique manifestation of diaphragm injury in COVID-19 patients after mechanical ventilation. However, it remains unclear what the exact nature and location of diaphragm injury is. Additionally, it is largely unknown whether this injury affects the movement of the diaphragm, but this might have important clinical implications. Therefore, we aim at visualizing the tissue characteristics and movement of the diaphragm in COVID-19 patients who recently received long-term mechanical ventilation, other ICU patients and healthy controls, using magnetic resonance imaging (MRI). MRI of the diaphragm was already shown feasible in previous research from our group (article currently under review). New insights in the characteristics of diaphragm weakness and injury in COVID-19 patients and control ICU-patients will contribute to strategies to prevent it and monitor the diaphragm of patients under mechanical ventilation, which can contribute to better patient outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 19, 2023
• Est. primary completion date: January 19, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria In order to be eligible to participate in this study, a subject in the case group must meet

all of the following criteria:

• Invasive mechanical ventilation > 72 hours during current hospital admission
• Admitted for COVID-19-infection (n = 10)
• Currently negative COVID-19 PCR test
• Discharged from the ICU = 7 days ago
• Signed informed consent
• Age = 18 years In order to be eligible to participate in this study, a subject in the control group must

meet all of the following criteria:

• Signed informed consent
• Age = 18 years
• Similar age (max 5 years difference) and gender of one of the subjects in case group Exclusion criteria A potential subject for the case group who meets any of the following criteria will be

excluded from participation in this study:

• Known history of:
• Diaphragmatic injury or weakness prior to ICU stay
• COPD (GOLD IV)
• Neuromuscular disease (including pathology of the n. phrenicus)
• Connective tissue disease
• Chronic use of corticosteroids (>7.5 mg/day for at least 3 months before hospital admission)
• >10% weight loss within last 6 months prior to ICU admission
• Obesity (BMI > 30 kg/m2 at hospital admission)
• Known pregnancy
• Contraindications for MRI
• Electrical/metallic implants
• Claustrophobia
• Unable to hold breath for 10 seconds
• Hierarchical relation with one of the collaborating investigators
• Incapacitation
• Contraindications for the use of a Gadolinium based contrast agent for MRI
• Known eGFR < 30 ml/min/1.73m2
• Known history of allergic reactions to an MRI contrast medium
• Known history of allergic reactions requiring immediate treatment
• Known history of atopy
• Asthma These exclusion criteria are based on the guidelines for contrast agents from the European Society for Urogenital Radiology (http://www.esur.org/guidelines/).

Additional exclusion criteria for the case group, subset non-infected patients are:

• History of COVID-19-infection (confirmed with positive test)

Additional exclusion criteria for the control group are:

• History of mechanical ventilation > 24 hours
• History of COVID-19-infection (confirmed with positive test)

Related Conditions & MeSH terms

• Covid19
• Diaphragm Disease
• Infection

Intervention

Other:
• Contrast-enhanced MRI
Contrast-enhanced MRI
• Measurement of respiratory muscle force
Measurement of the maximum inspiratory and expiratory pressure.

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC, location VUmc	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of diaphragm tissue characteristics with tissue characteristics of the abdominal muscles		1 hour
Primary	Tissue characteristics of the diaphragm	Extracted from contrast enhanced imaging	1 hour
Primary	Movement of the diaphragm	Description of the movement of the diaphragm in 4D fashion.	1 hour
Secondary	Quantitative dynamic contrast enhanced imaging of the diaphragm	Application of modelling to describe tissue characteristics of the diaphragm using contrast inflow.	1 hour
Secondary	Correlation of movement and tissue characteristics of the diaphragm with measurements of maximum inspiratory and expiratory pressure		1 hour
Secondary	Correlation of movement and tissue characteristics of the diaphragm with clinical parameters	Clinical parameters include ventilator settings, biomarkers for inflammation (CRP, white blood cell count) during ICU admission, daily dosage of drugs known with adverse effects on respiratory muscles, fluid balance, protein intake, primary reason for ICU admission and weaning duration.	1 hour