Macrophage Programing in Acute Lung Injury: MiniBAL

NCT05767671 | Recruiting

• 1 other identifier: HS3076
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational clinical trial is to learn about the role white blood cells (macrophages) play in lung inflammation in people with Acute Respiratory Distress Syndrome (ARDS). The main questions it aims to answer are:

1. 1.How does the immune system respond to different kinds of lung injury and inflammation and how do those processes differ from each other?
2. 2.What roles do the cells that live in the lungs (macrophages) play in turning off inflammation? How does their role differ from other cells that are called to the lung to help repair injury (recruited macrophages)?
3. 3.Will more frequent testing of lung cell samples help reduce the time it takes to start treatment for ventilator-associated pneumonia (VAP) and therefore reduce the rates of initial therapy failure?
4. 4.Participants will be given 100% oxygen through the breathing machine (mechanical ventilator) for 3-5 minutes. This is called pre-oxygenation.
5. 5.A lung specialist (pulmonologist), a member of Dr. Janssen's research team, or respiratory therapist will place small amount of saline into the lung using a long catheter going through the breathing tube.
6. 6.The fluid will be removed with suction and will be sent to the laboratory for testing.
7. 7.This will be repeated two more times over the course of 10 days, or less if participants are taken off of the ventilator. The procedure will be performed no more than three times.
8. 8.Two nasal brushings will be taken from the participants' nose.
9. 9.Approximately 3 tablespoons of blood will be removed by putting a needle into the participants vein. This is the standard method used to obtain blood for tests. A total of 9 tablespoons will be taken for research purposes over the course of this study
10. 10.Data including the participants age, sex, severity of illness, and other medical conditions will be recorded to determine how these can affect the white blood cells.
11. 11.If bacteria are isolated from the fluid in the participants lung, the participants' physician may choose to place the participants on antibiotics to treat an infection.
12. 12.A follow-up phone call may be made by a member of the research team after discharge from the hospital. At this time, the participant may be invited to participate in the Post-ICU clinic at National Jewish Health.

Conditions

Acute Respiratory Distress Syndrome; Ventilator Associated Pneumonia

Outcome Measures

Primary Outcomes (4)

• Evaluate host response to ARDS

  Compare host response due to ARDS caused by COVID19 versus other forms of ARDS and to determine how resident and recruited macrophages influence inflammation during ARDS and how they differentially contribute to lung repair.

  Days on ventilator 1-2, 4-6 and 8-10

• Macrophage signaling

  1\. The host response to COVID19 includes a robust inflammatory response with exceedingly high levels of pro-inflammatory cytokines such as IL-6. We hypothesize that macrophage signaling plays a major role in these responses.

  Days on ventilator 1-2, 4-6 and 8-10

• Resident alveolar Macrophages

  2\. Resident alveolar macrophages will remain constant in number throughout the course of ARDS whereas recruited macrophages will increase in number and then ultimately undergo apoptosis as inflammation resolves. Alveolar macrophages will be isolated from mini BAL of ARDS subjects and mechanically ventilated controls. Macrophage subsets will be distinguished with flow cytometry and enumerated.

  Days on ventilator 1-2, 4-6 and 8-10

• Recruited versus resident macrophages

  3\. Recruited macrophages from ARDS subjects will be more pro-inflammatory than resident macrophages at early time points (i.e. days 1-2) and produce pro-reparative molecules at later time points. Macrophage subsets will be isolated using FACS and subjected to RNA sequencing. Pro-inflammatory and pro-reparative modules will be assessed in the data set expression of transcription factors reported to drive macrophage polarization (HIF-1α, NF-kB, STAT-1, STAT-3, STAT-6, PPARγ, PU.1) will be assessed. Macrophages from control subjects will be used to determine baseline activation and transcriptional status.

  Days on ventilator 1-2, 4-6 and 8-10

Secondary Outcomes (1)

• Ventilator associated pneumonia (VAP)

  Days on ventilator 1-2, 4-6 and 8-10

Study Arms (1)

Study Population Group

OTHER

People in the ICU on mechanical ventilation due to a diagnosis of ARDS or any other diagnosis that requires mechanical ventilation (following surgery, sepsis without lung involvement, seizures)

Other: Non-Bronchoscopic Mini Bronchoalveolar Lavage

Interventions

Non-Bronchoscopic Mini Bronchoalveolar Lavage OTHER

A minimally invasive technique frequently used in the ICU to obtain alveolar fluid samples from mechanically ventilated patients. The technique uses a commercially available telescoping catheter with a curved distal tip that allows the operator to direct the catheter into the right or left lung. The catheter is passed through an air-tight adapter on the distal end of the endotracheal tube and gently advanced to the desired lung until resistance is encountered. The inner catheter is then advanced until resistance is again encountered, signifying that the distal catheter tip is "wedged." 20ml of sterile saline is instilled into the catheter followed by 5 ml of air, and the fluid aspirated. Two additional 20ml aliquots of sterile saline are injected and aspirated in a similar fashion. Specimens are pooled and on average provide a combined volume of 10ml.

Study Population Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent (by LAR if subject unconscious or has altered mental status) prior to any study procedures. Verbal consent may be used as necessary
• Adults greater than 18 years of age
• Admission to the intensive care unit.
• Orally/nasally intubated or expected to be intubated within 48 hours

You may not qualify if:

• History of solid organ or bone marrow transplantation
• Severe or massive hemoptysis
• At significant risk for bleeding (INR \> 3 or PTT \> 3x normal)
• Presence of pneumomediastinum or pneumothorax on recent imaging
• Presence of an advanced directive with Do Not Intubate (DNI) status (Do Not Resuscitate (DNR) is acceptable)
• Morbid state or expected to survive less than 24 hours because of an advanced co-morbid medical condition in the opinion of the PI and/or clinical team and attending physician.
• Pregnancy

Sponsors & Collaborators

• William Janssen, MD: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Intermountain Health - St. Joseph's Hospital - National Jewish Health

Denver, Colorado, 80218, United States

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome; Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Olivia VerBurg

CONTACT

303-398-1201; verburgo@njhealth.org

William Janssen, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Section Head of Critical Care, Professor of Medicine, Principle Investigator

Model Details: The population to be studied are patients identified to have ARDS, admitted to the intensive care unit, and placed on a mechanical ventilator. Control subjects will be individuals on mechanical ventilation for non-pulmonary reasons (i.e. following surgery, sepsis without lung involvement). A total of 56 subjects will be enrolled. As described below (in Research Methods and Enrollment) a 2:1 ratio of ARDS to control subjects will be targeted.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 14, 2023
• Study Start: April 10, 2020
• Primary Completion (Estimated): September 18, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)