4DX Functional Lung Imaging in the Diagnosis of Chronic Lung Allograft Dysfunction After Lung Transplantation

This is a pilot study to determine the utility of Novel Functional Lung Imaging and Ventilation (4DxV) Analysis software in measurement of lung ventilation abnormalities and diagnosis of chronic lung allograft dysfunction (CLAD) after lung transplantation.

Study Overview

• Status: Completed
• Conditions: Lung Transplant; Complications
• Intervention / Treatment: Diagnostic test: Fluoroscopic chest imaging with 4Dx technology software analysis

Detailed Description

This is a pilot study to determine the feasibility and utility of Novel Functional Lung Imaging and Ventilation (4DxV) Analysis software in measurement of lung ventilation abnormalities and diagnosis of CLAD after lung transplantation. 4DxV is a technology developed by 4Dx (4Dx Limited, Melbourne, Australia and Los Angeles, CA) and is a novel computational approach to the data obtained from standard fluoroscopic imaging that measures tissue motion of the lung at all locations and in all phases of breath. These motion measurements are used to calculate 4-dimensional ventilation (4DxV) of lung tissue to provide variety of outputs. The investigators will establish the sensitivity, specificity, and accuracy of this technology in diagnosis of CLAD compared to CT scan and pulmonary function results in patients with a known diagnosis of CLAD based on established diagnostic criteria.

The investigators will test the following hypotheses:

1. 4DxV scans will be able to detect quantitative ventilation abnormalities in patients with established CLAD and the severity of the abnormalities will correlate with severity of PFT decline
2. 4DxV will be able to diagnose patients with CLAD of the bronchiolitis obliterans syndrome (BOS) phenotype grades 0 (CLAD free) vs grades 1-3

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Greater than or equal to 18 years of age at the time of written informed consent
2. Recipient of a first bilateral lung transplantation performed at Duke University at least one year prior to written informed consent

3. Computed tomography (CT) scan of the chest performed at Duke as standard of care after transplantation but within 1 year prior to written informed consent 4a. CLAD grades 1, 2,or 3 (per ISHLT 2014 criteria [Meyer et al 2014]) prior to or at the time of screening

   • Grade 1 is defined as a fractional decrease in FEV1 to 66-80% of post-transplant baseline FEV1
   • Grade 2 is defined as a fractional decrease in FEV1 to 51%-65% of post-transplant baseline FEV1
   • Grade 3 is defined as a fractional decrease in FEV1 to <= 50% of post-transplant baseline FEV14b. CLAD free status (defined as most recent FEV1 at the time of screening >90% of post-transplant baseline FEV1)

Exclusion Criteria:

1. Recipients of a single lung transplant
2. Recipients of a redo-lung transplant
3. Recipients of bone marrow or stem cell transplant
4. Recipients of a multi-organ transplant
5. Patients with hospital admissions(excluding admissions for planned treatment of the CLAD and/or rejection)within one month of screening.
6. Patients who are unable to lie flat on the fluoroscopy table
7. Pregnant women (by subject's verbal report). Lung transplant recipients are routinely counseled to avoid pregnancy due to the teratogenic effects of necessary immunosuppressant medications. Pregnancy after lung transplantation is therefore extremely rare. As this is a minimal risk study which does not involve an experimental therapy, invasive devices, or increased risk procedures, pregnancy testing is deemed unnecessary for this population for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Participants who underwent a lung transplant at Duke; Participants will undergo fluoroscopic chest imaging with 4Dx technology software analysis

Diagnostic test: Fluoroscopic chest imaging with 4Dx technology software analysis; 4DxV utilizes a novel software algorithm to analyze data from cinefluoroscopy images to calculate regional ventilation and pulmonary function changes. Cinefluorography uses a fluorescent screen with X-rays to make real-time moving images the lung described below. This is the same x-ray fluoroscopy that is used in clinical imaging and the fluoroscopic imaging time is approximately 1 minute leading to an effective radiation dose of 2 mSv (200 mRem). This is significantly lower that the radiation exposure from a standard chest CT. Fluoroscopy images are acquired at each of five views for approximately enough time to capture at least one complete, continuous breath. The subject is required to remain in the same position for each of the five fluoroscopy imaging sequences. These images will be analyzed by the novel 4Dx technology to provide the 4Dx lung function analysis report.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation defect percentage (VDP) as measured by XV lung ventilation analysis software	Determine the VDP using XV Lung Ventilation Analysis Software to quantify ventilation in lung transplant patients	At least one year after lung transplantation
Regional ventilation heterogeneity percentage as measured by XV lung ventilation analysis software	Determine the ventilation heterogeneity percentage using XV Lung Ventilation Analysis Software to quantify ventilation in lung transplant patients	At least one year after lung transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculation of Bronchiolitis Obliterans Syndrome (BOS) Stage based on FEV1 decline	Determine BOS stage based on subject's pulmonary function test measurements of percent FEV1 decline compared to post transplant baseline FEV1	At least one year after lung transplantation

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: 4DMedical
• Investigators: Principal Investigator: Azfar Ali, MD, Duke University

Publications and helpful links

General Publications

• Meyer KC, Raghu G, Verleden GM, Corris PA, Aurora P, Wilson KC, Brozek J, Glanville AR; ISHLT/ATS/ERS BOS Task Force Committee; ISHLT/ATS/ERS BOS Task Force Committee. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014 Dec;44(6):1479-503. doi: 10.1183/09031936.00107514. Epub 2014 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Lung Transplantation; Chronic Lung Allograft Dysfunction
• Other Study ID Numbers: Pro00103179

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: Yes