Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant

Respiratory Failure Clinical Trial

— DIASPORA  

Official title:

Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03667027
• Other study ID #: 18-5660
• Status: Recruiting
• Start date: April 1, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: April 2023
• Source: University Health Network, Toronto
• Contact: Rongyu (Cindy) Jin
• Phone: 416-340-4800
• Email: rongyu.jin[@]uhn.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 30, 2024
• Est. primary completion date: October 30, 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (Cases):

• Receiving a respiratory support modality as a bridge to lung transplantation
• Formally listed for transplantation

Inclusion Criteria (Control Group 1):

• Undergoing lung transplantation for either obstructive or restrictive lung disease

Inclusion Criteria (Control Group 2):

• Undergoing elective thoracic surgery without any prior history of chronic pulmonary parenchymal disease

Exclusion Criteria (Cases and Controls):

• Previously diagnosed with neuromuscular disorder
• Received invasive mechanical ventilation for >48 hours in the preceding four weeks
• Thoracic cage deformity

Related Conditions & MeSH terms

• Diaphragm Injury
• Mechanical Ventilation Complication
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Device:
• Respiratory support
Mechanical ventilation or extracorporeal life support

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in diaphragm thickness and thickening fraction in patients using MV and patients using ECLS	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	Change from baseline diaphragm thickness and thickening fraction at 7 days after lung transplant
Secondary	Correlate changes in diaphragm thickness and histological features of diaphragm dysfunction	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	Assessed immediately after transplantation
Secondary	Biomarkers for diaphragm dysfunction	Biomarkers to be assessed are: skeletal troponin-I and markers of systemic inflammation (IL-1, IL-6, Tumor Necrosis Factor (TNF)-alpha)	Assessed immediately before transplantation