Clinical trial NCT03667027: Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant
Official title: Diaphragm Structure and Pathobiology in Patients Being Bridged to Lung Transplant
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diaphragm Injury
Respiratory Failure
Mechanical Ventilation Complication
Keywords: Diaphragm Dysfunction
Acute Respiratory Failure
Mechanical Ventilation
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: The Hospital for Sick Children
First posted: 2018-09-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in diaphragm thickness and thickening fraction in patients using MV and patients using ECLS
timeFrame: Change from baseline diaphragm thickness and thickening fraction at 7 days after lung transplant
Secondary outcomes:
measure: Correlate changes in diaphragm thickness and histological features of diaphragm dysfunction
timeFrame: Assessed immediately after transplantation
measure: Biomarkers for diaphragm dysfunction
timeFrame: Assessed immediately before transplantation
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
Study officials:
affiliation: University Health Network, Toronto
name: Ewan Goligher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: