Constrictive BronchiolitisNCT04489758
4DX for the Diagnosis of Constrictive Bronchiolitis
A study testing X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis in people with Constrictive Bronchiolitis, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
Constrictive bronchiolitis is an uncommon lung disease that has been described in Veterans of conflicts in Iraq and Afghanistan. Although these Veterans have evidence of constrictive bronchiolitis on lung biopsies, non-invasive tests such as pulmonary function tests (PFTs) are often normal. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Constrictive Bronchiolitis
- What is being tested?
- X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jun 2021to 27 May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Constrictive bronchiolitis arm:
- Biopsy demonstrating constrictive bronchiolitis
- Prior CT Chest
- 18-60 years old
- < 1 pack year history of tobacco use
- Control arm:
Show all 10Show fewer
- 18-60 years old
- Prior CT Chest without evidence chronic lung disease as judged by a Pulmonologist
- No clinically significant dyspnea or functional limitations
- < 1 pack year history of tobacco use
Who cannot join
- Pregnancy (as determined by testing on the morning prior to fluoroscopy)
- Inability to undergo PFTs or fluoroscopy
- Inability to raise arms above a 90-degree angle
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Utility of a Novel Imaging Algorithm (4DX) for the Diagnosis of Constrictive Bronchiolitis
Constrictive bronchiolitis is an uncommon lung disease that has been described in Veterans of conflicts in Iraq and Afghanistan. Although these Veterans have evidence of constrictive bronchiolitis on lung biopsies, non-invasive tests such as pulmonary function tests (PFTs) are often normal. This study will determine whether analysis of fluoroscopy images using the 4Dx XV Ventilation Analysis software developed by 4D Medical will be able to detect constrictive bronchiolitis in Veterans better than PFTs.
Read the detailed description
Constrictive (or obliterative) bronchiolitis is a rare pulmonary disease characterized by subepithelial inflammatory and fibrotic narrowing of the bronchioles on histologic analysis, which often presents with nonspecific symptoms such as progressive dyspnea on exertion and nonproductive cough over weeks to months. Constrictive bronchiolitis may be triggered by autoimmune disease, chronic allograft rejection in lung transplant recipients, graft versus host disease in stem cell transplant recipients, viral illness, or inhaled toxins. Although pulmonary function tests (PFTs) may be helpful for the diagnosis of constrictive bronchiolitis, a study performed by King and colleagues in 2009 found that many Veterans with biopsy-proven constrictive bronchiolitis had normal PFTs. Thus, for these patients, more sensitive methods of noninvasive testing are needed.
4Dx XV Ventilation Analysis is a new imaging analysis algorithm which utilizes standard fluoroscopy to quantify ventilation with sufficient fidelity to identify regional differences. Fluoroscopic images of a single tidal breath are obtained at 5 distinct angles (direct AP, +/- 36 degrees, and +/- 72 degrees). Readouts from the 4Dx XV Ventilation Analysis include absolute value of total lung ventilation, heterogeneity of lung ventilation, a frequency distribution of lung ventilation as a line plot, and a regional map of lung ventilation. In addition, an expiratory time constant (time to exhale 63% of the tidal volume), heterogeneity of the expiratory time constant, frequency distribution of expiratory time constant as a line plot, and a regional map of expiratory time constant are also calculated. Pilot studies performed by 4D Medical show data generated by the 4Dx XV Ventilation Analysis software applied to fluoroscopy is reproducible in individuals with normal lung function and the heterogeneity index increases in individuals undergoing radiation therapy.
The investigators hypothesize that the 4Dx XV Ventilation Analysis program, when applied to standard fluoroscopic images, is more sensitive for the diagnosis of constrictive bronchiolitis than PFTs in Veterans with constrictive bronchiolitis. Specific metrics that will be evaluated with the software include ventilation heterogeneity and expiratory phase constants, among other metrics. Endpoints will be compared during tidal breathing and a full exhalation to residual volume from functional residual capacity.
- Conditions
- Constrictive Bronchiolitis
- Being tested
- X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis
- Keywords
- fluoroscopy, X-ray velocimetry
- Medical subject headings
- Bronchiolitis Obliterans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
X-ray velocimetry analyzed by 4Dx XV Ventilation AnalysisDiagnostic test
Fluoroscopy will be performed for a complete tidal breath and full exhalation at 5 angles (AP, +/- 36 degrees from AP, and +/- 72 degrees from AP) while the patient's arms are raised overhead. 4Dx XV Ventilation Analysis software will be used to analyze these images. Both groups will also undergo pulmonary function testing and take a questionnaire regarding respiratory symptoms.
| Study group | Role | What they receive |
|---|---|---|
| Constrictive Bronchiolitis | Experimental | Veterans with surgical lung biopsy-proven constrictive bronchiolitis Receives: Diagnostic Test: X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis |
| Controls | Active comparator | Control patients with minimal smoking history and no chronic lung disease or respiratory symptoms Receives: Diagnostic Test: X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
X-ray velocimetry results
Heterogeneity of ventilation as detected by X-ray velocimetry
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2020
- Study start25 Jun 2021
- Primary completion27 May 2022
- Study completion27 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Constrictive BronchiolitisStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 4Dx XV Ventilation Analysis applied to fluoroscopic images
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- 4DMedical
- Responsible party
- Principal investigator, Bradley Richmond, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04489758
- Sponsor's protocol ID
- 200473
- Status last verified
- Aug 2022
- First submitted
- 23 Jul 2020
- Last updated
- 30 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
King MS, Eisenberg R, Newman JH, Tolle JJ, Harrell FE Jr, Nian H, Ninan M, Lambright ES, Sheller JR, Johnson JE, Miller RF. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011 Jul 21;365(3):222-30. doi: 10.1056/NEJMoa1101388.
PubMed 21774710Richmond BW, Lester MG, Lui V, Dusting J, Raju S, Snell GI, Blackburn JB, Douglas K, Miller RF, Siddharthan T, Fouras A. X-ray velocimetry provides temporally and spatially-resolved biomarkers of lung ventilation in small airways disease. Respir Res. 2025 Jul 2;26(1):226. doi: 10.1186/s12931-025-03295-6.
PubMed 40604808
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Utility of a Novel Imaging Algorithm (4DX) for the Diagnosis of Constrictive Bronchiolitis
- ClinicalTrials.gov ID
- NCT04489758
- Acronym / sponsor ID
- 200473
- Conditions
- Constrictive Bronchiolitis
- Keywords
- fluoroscopy, X-ray velocimetry
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- 4DMedical
- Study start
- 25 Jun 2021 (actual)
- Primary completion
- 27 May 2022 (actual)
- Study completion
- 27 May 2022 (actual)
- First posted
- 28 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Constrictive bronchiolitis is an uncommon lung disease that has been described in Veterans of conflicts in Iraq and Afghanistan. Although these Veterans have evidence of constrictive bronchiolitis on lung biopsies, non-invasive tests such as pulmonary function tests (PFTs) are often normal. This study will determine whether analysis of fluoroscopy images using the 4Dx XV Ventilation Analysis software developed by 4D Medical will be able to detect constrictive bronchiolitis in Veterans better than PFTs.
Detailed description
Constrictive (or obliterative) bronchiolitis is a rare pulmonary disease characterized by subepithelial inflammatory and fibrotic narrowing of the bronchioles on histologic analysis, which often presents with nonspecific symptoms such as progressive dyspnea on exertion and nonproductive cough over weeks to months. Constrictive bronchiolitis may be triggered by autoimmune disease, chronic allograft rejection in lung transplant recipients, graft versus host disease in stem cell transplant recipients, viral illness, or inhaled toxins. Although pulmonary function tests (PFTs) may be helpful for the diagnosis of constrictive bronchiolitis, a study performed by King and colleagues in 2009 found that many Veterans with biopsy-proven constrictive bronchiolitis had normal PFTs. Thus, for these patients, more sensitive methods of noninvasive testing are needed.
4Dx XV Ventilation Analysis is a new imaging analysis algorithm which utilizes standard fluoroscopy to quantify ventilation with sufficient fidelity to identify regional differences. Fluoroscopic images of a single tidal breath are obtained at 5 distinct angles (direct AP, +/- 36 degrees, and +/- 72 degrees). Readouts from the 4Dx XV Ventilation Analysis include absolute value of total lung ventilation, heterogeneity of lung ventilation, a frequency distribution of lung ventilation as a line plot, and a regional map of lung ventilation. In addition, an expiratory time constant (time to exhale 63% of the tidal volume), heterogeneity of the expiratory time constant, frequency distribution of expiratory time constant as a line plot, and a regional map of expiratory time constant are also calculated. Pilot studies performed by 4D Medical show data generated by the 4Dx XV Ventilation Analysis software applied to fluoroscopy is reproducible in individuals with normal lung function and the heterogeneity index increases in individuals undergoing radiation therapy.
The investigators hypothesize that the 4Dx XV Ventilation Analysis program, when applied to standard fluoroscopic images, is more sensitive for the diagnosis of constrictive bronchiolitis than PFTs in Veterans with constrictive bronchiolitis. Specific metrics that will be evaluated with the software include ventilation heterogeneity and expiratory phase constants, among other metrics. Endpoints will be compared during tidal breathing and a full exhalation to residual volume from functional residual capacity.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 4Dx XV Ventilation Analysis applied to fluoroscopic images
| Arm | Type | Receives |
|---|---|---|
| Constrictive Bronchiolitis | Experimental | Diagnostic Test: X-ray velocimetry analyzed by 4Dx XV Ventilation AnalysisVeterans with surgical lung biopsy-proven constrictive bronchiolitis |
| Controls | Active comparator | Diagnostic Test: X-ray velocimetry analyzed by 4Dx XV Ventilation AnalysisControl patients with minimal smoking history and no chronic lung disease or respiratory symptoms |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Biopsy demonstrating constrictive bronchiolitis
- Prior CT Chest
- 18-60 years old
- < 1 pack year history of tobacco use
- 18-60 years old
Key exclusion criteria (3 listed)
- Pregnancy (as determined by testing on the morning prior to fluoroscopy)
- Inability to undergo PFTs or fluoroscopy
- Inability to raise arms above a 90-degree angle
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| X-ray velocimetry analyzed by 4Dx XV Ventilation AnalysisFluoroscopy will be performed for a complete tidal breath and full exhalation at 5 angles (AP, +/- 36 degrees from AP, and +/- 72 degrees from AP) while the patient's arms are raised overhead. 4Dx XV Ventilation Analysis software will be used to analyze these images. Both groups will also undergo pulmonary function testing and take a questionnaire regarding respiratory symptoms. | Diagnostic test | Constrictive Bronchiolitis, Controls |
Primary outcome
X-ray velocimetry results
Time frame: 1 month
Heterogeneity of ventilation as detected by X-ray velocimetry
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2022.
- Background: PubMed 21774710King MS, Eisenberg R, Newman JH, Tolle JJ, Harrell FE Jr, Nian H, Ninan M, Lambright ES, Sheller JR, Johnson JE, Miller RF. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011 Jul 21;365(3):222-30. doi: 10.1056/NEJMoa1101388.
- Derived from this study: PubMed 40604808Richmond BW, Lester MG, Lui V, Dusting J, Raju S, Snell GI, Blackburn JB, Douglas K, Miller RF, Siddharthan T, Fouras A. X-ray velocimetry provides temporally and spatially-resolved biomarkers of lung ventilation in small airways disease. Respir Res. 2025 Jul 2;26(1):226. doi: 10.1186/s12931-025-03295-6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis in people with Constrictive Bronchiolitis, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
X-ray velocimetry results (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04489758, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2022.