Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant (DIASPORA)

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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Failure; Mechanical Ventilation Complication; Diaphragm Injury
• Intervention / Treatment: Device: Respiratory 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 Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Rongyu (Cindy) Jin; Phone Number: 7613 416-340-4800; Email: rongyu.jin@uhn.ca

Study Locations

• Canada
  • Toronto, Canada
    • Recruiting
    • Toronto General Hospital
    • Contact: Jenna Wong, MSc; Phone Number: 7613 4163404800; Email: jenna.wong@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute respiratory failure awaiting lung transplantation who are being bridged to lung transplantation either by mechanical ventilation or extracorporeal life support.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients undergoing LTx with respiratory failure (cases); Patients are receiving a respiratory support modality (mechanical ventilation and/or extracorporeal life support) as a bridge to lung transplantation (LTx).	Device: Respiratory support; Mechanical ventilation or extracorporeal life support
Patients undergoing LTx without prior respiratory support; Patients undergoing lung transplantation but do not require prior bridging respiratory support.
Elective thoracic surgical patients; Patients undergoing elective thoracic surgery for planned lung or esophageal resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: The Hospital for Sick Children
• Investigators: Principal Investigator: Ewan Goligher, MD, PhD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Mechanical Ventilation; Acute Respiratory Failure; Diaphragm Dysfunction
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: 18-5660

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No