Clinical trial NCT04892719: 4DX Functional Lung Imaging in the Diagnosis of Chronic Lung Allograft Dysfunction After Lung Transplantation
Official title: 4DX Functional Lung Imaging in the Diagnosis of Chronic Lung Allograft Dysfunction After Lung Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lung Transplant; Complications
Keywords: Lung Transplantation
Chronic Lung Allograft Dysfunction
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: 4DMedical
First posted: 2021-05-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study uses a case control design and approximately 15 lung transplant recipients will be enrolled (10 CLAD cases/5 CLAD free controls). The study procedures will be performed during a single research visit.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Ventilation defect percentage (VDP) as measured by XV lung ventilation analysis software
timeFrame: At least one year after lung transplantation
measure: Regional ventilation heterogeneity percentage as measured by XV lung ventilation analysis software
timeFrame: At least one year after lung transplantation
Secondary outcomes:
measure: Calculation of Bronchiolitis Obliterans Syndrome (BOS) Stage based on FEV1 decline
timeFrame: At least one year after lung transplantation
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Azfar Ali, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.