Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant

Recruiting

• Conditions: Mechanical Ventilation Complication; Diaphragm Injury; Respiratory Failure
• Interventions: Device: Respiratory support

• Registration Number: NCT03667027
• Lead Sponsor: University Health Network, Toronto

Brief Summary

This study is designed to characterize the changes in diaphragm structure, function and biology during bridging to lung transplant by mechanical ventilation or extracorporeal life support.

Detailed Description

Mechanical ventilation has been linked to diaphragm injury and dysfunction. During mechanical ventilation, the amount of breathing work done by the diaphragm is unpredictable: the diaphragm could be completely rested, or it could be overworked. Either of these possibilities may cause injury to the diaphragm. Patients with an injured and dysfunctional diaphragm have greater difficulty weaning from mechanical ventilation - they become too weak to breathe. However, little is known about the relationship between changes in the diaphragm and the histological (structure of cells and tissue) basis of these changes. The investigators have developed a new technique employing beside ultrasound to measure diaphragm thickness. This allows them to observe changes in diaphragm muscle structure and function.

The goal of the study is to determine whether different forms of respiratory support (mechanical ventilation vs extracorporeal life support) lead to different degrees of diaphragm injury and to compare changes in the diaphragm seen on ultrasound to changes in the diaphragm tissues under a microscope. This will help the investigators to confirm the best way to avoid diaphragm injury and to understanding the meaning of diaphragm ultrasound images.

Study Timeline

• Study First Submitted: 2018-08-31
• Study First Submitted QC: 2018-09-10
• Study First Posted: 2018-09-12
• Study Start: 2019-04-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-11
• Primary Completion: 2025-08-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients undergoing LTx with respiratory failure (cases)	Respiratory support	Patients are receiving a respiratory support modality (mechanical ventilation and/or extracorporeal life support) as a bridge to lung transplantation (LTx).

Primary Outcome Measures

Name	Time	Method
Difference in diaphragm thickness and thickening fraction in patients using MV and patients using ECLS	Change from baseline diaphragm thickness and thickening fraction at 7 days after lung transplant	Diaphragm thickness and injury score will be tested for an interaction between the bridging modality (MV vs. ECLS) and the duration of exposure to the modality on the degree of diaphragm injury and atrophy

Secondary Outcome Measures

Name	Time	Method
Correlate changes in diaphragm thickness and histological features of diaphragm dysfunction	Assessed immediately after transplantation	Histological features to be assessed are: myofibril cross-sectional area, muscle fiber type, presence of cellular infiltrates, myofiber necrosis and regeneration, autophagy and fibro-fatty infiltration
Biomarkers for diaphragm dysfunction	Assessed immediately before transplantation	Biomarkers to be assessed are: skeletal troponin-I and markers of systemic inflammation (IL-1, IL-6, Tumor Necrosis Factor (TNF)-alpha)

Trial Locations

Locations (1)

Toronto General Hospital; 🇨🇦 Toronto, Canada