Idiopathic Pulmonary FibrosisRadiomicsNCT06323876
The Role of Quantitative CT and Radiomic Biomarkers for Precision Medicine in Pulmonary Fibrosis
An observational study of Idiopathic Pulmonary Fibrosis, run by University of Virginia at 1 site in United States.
Trial summary
This observational study involves obtaining 2 chest CT scans; a historical baseline CT within ±1 year of enrollment into PRECISIONS, and a follow-up CT (either historical or prospective) 12 months ± 180 days after the baseline CT. Read more about this study
- Who is it for?
- Ages 40 to 101 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- HRCT and Blood Draw
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2024to May 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 40 to 101 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients diagnosed with Pulmonary Fibrosis as described above in inclusion criteria.
Who may be able to join
- ≥ 40 years of age
- Diagnosed with IPF according to 2018 ATS/ERS/JRS/ALAT confirmed by the enrolling investigator
- Signed informed consent
Who cannot join
- Pregnancy or planning to become pregnant
- Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year during study participation*
- Significant medical, surgical or psychiatric illness that in the opinion of the investigator would affect subject safety or potential to complete the research study
- A woman is considered to be of childbearing potential if she is post-monarchical, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
- Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Diana Hsu, MA contact
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Roselove Asare, MA, 434-243-6074, rnn3b@uvahealth.org
Diana Hsu, MA, NBR2DF@uvahealth.org
About this study
This observational study involves obtaining 2 chest CT scans; a historical baseline CT within ±1 year of enrollment into PRECISIONS, and a follow-up CT (either historical or prospective) 12 months ± 180 days after the baseline CT. Many IPF patients will have a CT scan every 12 months for disease monitoring and cancer screening. Participants will have the option to share historical CTs only or they can choose to have a research CT done for the follow-up scan, if a scan for clinical purposes is not available.
Read the detailed description
Idiopathic pulmonary fibrosis (IPF) remains deadly despite two FDA-approved therapies. Forced vital capacity (FVC), a one-dimensional assessment of lung function that requires three effort-dependent and error-prone maneuvers, is the standard for evaluating disease severity and monitoring progression. FVC indirectly measures disease activity and is thus insensitive to subtle change. These limitations hamper therapeutic trials. The Gender, Age, and Physiology (GAP) score improves on FVC alone and is the most used scoring model for prognostication, but gender and age aren't influenced by treatment. Modifiable intermediate molecular markers and other metrics for assessing disease severity and progression remain unmet needs for aiding drug development and clinical decision-making. Computed tomography (CT) captures morphologic patterns and the extent of fibrosis noninvasively. Advances in quantitative CT enable objective detection and quantitation of anatomy, and highly dimensional image features, often termed radiomic, can identify sub-visual characteristics. The investigators seek to evaluate radiomic features alone and in conjunction with other disease dimensions for prognostication and response to treatment in IPF.
The investigators overall objectives are to identify and validate radiologic features, such as total extent of lung fibrosis, for disease activity and intermediate response to therapy, and understand where to position these powerful markers. The investigators hypothesize that DTA scores will contribute to prediction of disease progression and that molecular markers will enhance that performance.
Aim 1: The investigators will validate quantitative CT and radiomic markers for disease progression by independent replication in separate cohorts. The investigators hypothesize that quantitative CT markers will predict disease progression in UVA/Chicago cohorts. Baseline and subsequent CT scans have been voluntarily collected in many PFF-PR cases. The investigators propose collection of 1-year HRCTs in UVA/Chicago participants to evaluate: a) the prognostic value of baseline quantitative CT and radiomic markers (i.e. DTA) in predicting time to progression defined as either 10% relative decline in FVC, lung transplant, or death from any cause, b) associations between changes in CT biomarkers on sequential CT and changes in 1-year FVC and DLCO, and c) change in CT associated with drug treatment. This aim will establish the relative and synergistic value of CT to established physiologic markers.
Aim 2: The investigators will determine if candidate genetic variants for IPF susceptibility and survival are associated with the DTA score and improve predictive performance for survival. The investigators hypothesize that variants in MUC5B, TOLLIP, and Telomere lengths (TL) will enhance DTA fibrosis score associations with progression-free survival in IPF. The investigators will perform a cross-sectional analysis of PFF-PR cases comparing quantitative CT and radiomic markers at baseline with and without "at risk" genotypes for association with severity and progression (decline in FVC over time). This will ascertain what markers improve performance of the DTA fibrosis extent scores using Cox regression analysis and accuracy metrics from Aim 1. Findings will be replicated in UVA/Chicago cohort and in the prospective PRECISIONS cohort. This aim will establish the additive value of genetic markers.
Aim 3: The investigators will assess whether DTA and radiomic markers are additive/synergistic with plasma protein and blood transcriptome markers for disease progression. The investigators hypothesize that selected protein and transcriptomic markers will prove additive to DTA fibrosis extent for prediction of progression-free survival whereas other markers correlated with DTA will not. The investigators have chosen published markers from a 4-protein panel signature, along with CCL18, as examples, given their current level of replication and promise. The investigators will also include a 25-gene FVC predictor for disease progression. Similar analyses, as outlined in Aims 1 and 2, will determine their additive information value.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- HRCT, Blood Draw
- Keywords
- CT, biomarkers, gene expression, radiomic markers
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HRCTDiagnostic test
High resolution computed tomography (HRCT) scan is a medical imaging technique used to obtain detailed internal images of the body. HRCT images will be obtained at 0 and 12 months.
Blood DrawDiagnostic test
During blood draw, someone uses a needle to take blood from a vein, usually in your arm.
| Study group | Role | What they receive |
|---|---|---|
| University of Chicago | This cohort will have prior consent to the Natural History of Interstitial Lung Disease, which is an ongoing, longitudinal cohort of patients with clinically diagnosed ILD, including IPF. Patients are recruited from University of Chicago Interstitial Lung Disease Program during their clinic visit. Blood, plasma, and serum samples are collected upon enrollment and stored in a biorepository at University of Chicago. Subsets of patients have repeat blood draw at return clinic visits for specific research studies. The investigators propose collection of 1-year HRCTs, FVC, and DLCO. Receives: Diagnostic Test: HRCT; Diagnostic Test: Blood Draw | |
| University of Virginia | This cohort will have prior consent to the Natural History of Interstitial Lung Disease, which is an ongoing, longitudinal cohort of patients with clinically diagnosed ILD, including IPF. Patients are recruited from the UVA Interstitial Lung Disease Program during their clinic visit. Blood, plasma, and serum samples are collected upon enrollment and stored in a biorepository at UVA (Pinn Hall RM#2232B, IRB#20937). Subsets of patients have repeat blood draw at return clinic visits for specific research studies. The investigators propose collection of 1-year HRCTs, FVC, and DLCO. Receives: Diagnostic Test: HRCT; Diagnostic Test: Blood Draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Derivation of DTA in IPF only cases from the PFF-PR and its associations with disease severity and outcomes.
Driven texture analysis (DTA) is a machine learning method capable of automatic detection and quantification of lung fibrosis on HRCT. It is trained to discriminate fibrosis using radiologist-identified image regions demonstrating normal lung parenchyma and usual interstitial pneumonia patterns.
Changes in Forced Vital Capacity (FVC) measured in liters, reflect increased elastic recoil caused by fibrosis. We will use linear-mixed effects models with random intercept to examine associations of repeated DTA-fibrosis scores with repeated percent predicted FVC measurements over time (12 months minimum). This approach will provide a more precise estimate, power, and account for baseline FVC at an individual level which has implications of how rapid a decline we anticipate. This is the most common approach to examine longitudinal changes of FVC in IPF studies. FVC decline greater than 10% has been shown to be prognostic of worse survival and is a common endpoint in IPF clinical trials.
Measured: 12 months
Determine whether known IPF-risk genetic variants are associated with DTA score.
This is a cross-sectional analysis to determine whether genetic variants that confer higher risk of disease and progression are associated with higher DTA scores from CT.
Measured: 12 months
Identify novel genetic variants that associate with DTA score progression.
Determine novel genetic variants that indicate higher risk of disease progression and are associated with higher DTA scores.
Measured: 12 months
Determine if DTA or any constituent radiomic features correlate with select plasma proteins.
MMP-7, CA-125, YKL, OPN, CCL18 are plasma proteins that have been shown to be associated with risk and prognosis in IPF.
Measured: 12 months
Determine if DTA or any of constituent radiomic features correlate with transcriptomic
We have previously published a transcriptomic classifier that is predictive of FVC decline in IPF.
Measured: 12 months
Determine the best combination of markers (DTA, proteins and transcriptome) for machine learning algorithms for AUC evaluation of ROCs on all 3 cohorts.
12-month FVC decline is a validated marker of disease progression in IPF as it's predictive of worse mortality. Receiver operating characteristic curve (ROC) is an analytical method, represented as a graph, that is used to evaluate the performance of a binary diagnostic classification method. The diagnostic test results need to be classified into one of the clearly defined dichotomous categories, such as the presence or absence of a disease. Area under the ROC curve (AUC) measures the entire two-dimensional area underneath the entire ROC curve.
Measured: 12 months
Secondary outcomes (2)
Determine associations of changes in DTA scores with 12-month changes in FVC and DLCO.
FVC (L) and diffusing capacity of the lungs for carbon monoxide (DLCO) have been shown to be validated markers of disease progression in IPF. DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. The normal range for DLCO: 80-120% of its predicted value for men. 76-120% of its predicted value for women.
Measured: 12 months
Determine associations of changes in DTA scores with drug treatment (i.e., antifibrotics)
Changes in DTA scores have been shown correlate strongly with changes in lung function. By establishing that changes in DTA scores occur in response to patients with IPF who start antifibrotic therapy, will provide supportive evidence of DTA as a potential tool to track treatment responses.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2024
- Study start20 Jun 2024
- Primary completionMay 2028 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Imre Noth, MD, University of Virginia
- Investigators
- Noth Imre, MD, Principal investigator, Division of Pulmonary and Critical CareJohn Kim, Principal investigator, Division of Pulmonary and Critical Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06323876
- Sponsor's protocol ID
- HSR231590
- Other IDs
- R01HL171918
- Acronym
- Radiomics
- Status last verified
- Aug 2024
- First submitted
- 7 Mar 2024
- Last updated
- 16 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Plan to share de-identified dicom images with Ambrahealth for CT analysis
Publications
Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018 May 10;378(19):1811-1823. doi: 10.1056/NEJMra1705751. No abstract available.
PubMed 29742380Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, King TE Jr, Collard HR. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012 May 15;156(10):684-91. doi: 10.7326/0003-4819-156-10-201205150-00004.
PubMed 22586007Podolanczuk AJ, Kim JS, Cooper CB, Lasky JA, Murray S, Oldham JM, Raghu G, Flaherty KR, Spino C, Noth I, Martinez FJ; PRECISIONS Study Team. Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial. BMC Pulm Med. 2022 Dec 13;22(1):475. doi: 10.1186/s12890-022-02281-8.
PubMed 36514019Humphries SM, Swigris JJ, Brown KK, Strand M, Gong Q, Sundy JS, Raghu G, Schwarz MI, Flaherty KR, Sood R, O'Riordan TG, Lynch DA. Quantitative high-resolution computed tomography fibrosis score: performance characteristics in idiopathic pulmonary fibrosis. Eur Respir J. 2018 Sep 17;52(3):1801384. doi: 10.1183/13993003.01384-2018. Print 2018 Sep.
PubMed 30139770Humphries SM, Yagihashi K, Huckleberry J, Rho BH, Schroeder JD, Strand M, Schwarz MI, Flaherty KR, Kazerooni EA, van Beek EJR, Lynch DA. Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of Fibrosis at Baseline and 15-Month Follow-up. Radiology. 2017 Oct;285(1):270-278. doi: 10.1148/radiol.2017161177. Epub 2017 May 10.
PubMed 28493789King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18.
PubMed 24836312Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82. doi: 10.1056/NEJMoa1402584. Epub 2014 May 18.
PubMed 24836310Reichmann WM, Yu YF, Macaulay D, Wu EQ, Nathan SD. Change in forced vital capacity and associated subsequent outcomes in patients with newly diagnosed idiopathic pulmonary fibrosis. BMC Pulm Med. 2015 Dec 29;15:167. doi: 10.1186/s12890-015-0161-5.
PubMed 26714746Schmidt SL, Tayob N, Han MK, Zappala C, Kervitsky D, Murray S, Wells AU, Brown KK, Martinez FJ, Flaherty KR. Predicting pulmonary fibrosis disease course from past trends in pulmonary function. Chest. 2014 Mar 1;145(3):579-585. doi: 10.1378/chest.13-0844.
PubMed 24231810Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.
PubMed 28388260
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Quantitative CT and Radiomic Biomarkers for Precision Medicine in Pulmonary Fibrosis
- ClinicalTrials.gov ID
- NCT06323876
- Acronym / sponsor ID
- Radiomics / HSR231590
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- CT, biomarkers, gene expression, radiomic markers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 20 Jun 2024 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 21 Mar 2024 (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.
This observational study involves obtaining 2 chest CT scans; a historical baseline CT within ±1 year of enrollment into PRECISIONS, and a follow-up CT (either historical or prospective) 12 months ± 180 days after the baseline CT. Many IPF patients will have a CT scan every 12 months for disease monitoring and cancer screening. Participants will have the option to share historical CTs only or they can choose to have a research CT done for the follow-up scan, if a scan for clinical purposes is not available.
Detailed description
Idiopathic pulmonary fibrosis (IPF) remains deadly despite two FDA-approved therapies. Forced vital capacity (FVC), a one-dimensional assessment of lung function that requires three effort-dependent and error-prone maneuvers, is the standard for evaluating disease severity and monitoring progression. FVC indirectly measures disease activity and is thus insensitive to subtle change. These limitations hamper therapeutic trials. The Gender, Age, and Physiology (GAP) score improves on FVC alone and is the most used scoring model for prognostication, but gender and age aren't influenced by treatment. Modifiable intermediate molecular markers and other metrics for assessing disease severity and progression remain unmet needs for aiding drug development and clinical decision-making. Computed tomography (CT) captures morphologic patterns and the extent of fibrosis noninvasively. Advances in quantitative CT enable objective detection and quantitation of anatomy, and highly dimensional image features, often termed radiomic, can identify sub-visual characteristics. The investigators seek to evaluate radiomic features alone and in conjunction with other disease dimensions for prognostication and response to treatment in IPF.
The investigators overall objectives are to identify and validate radiologic features, such as total extent of lung fibrosis, for disease activity and intermediate response to therapy, and understand where to position these powerful markers. The investigators hypothesize that DTA scores will contribute to prediction of disease progression and that molecular markers will enhance that performance.
Aim 1: The investigators will validate quantitative CT and radiomic markers for disease progression by independent replication in separate cohorts. The investigators hypothesize that quantitative CT markers will predict disease progression in UVA/Chicago cohorts. Baseline and subsequent CT scans have been voluntarily collected in many PFF-PR cases. The investigators propose collection of 1-year HRCTs in UVA/Chicago participants to evaluate: a) the prognostic value of baseline quantitative CT and radiomic markers (i.e. DTA) in predicting time to progression defined as either 10% relative decline in FVC, lung transplant, or death from any cause, b) associations between changes in CT biomarkers on sequential CT and changes in 1-year FVC and DLCO, and c) change in CT associated with drug treatment. This aim will establish the relative and synergistic value of CT to established physiologic markers.
Aim 2: The investigators will determine if candidate genetic variants for IPF susceptibility and survival are associated with the DTA score and improve predictive performance for survival. The investigators hypothesize that variants in MUC5B, TOLLIP, and Telomere lengths (TL) will enhance DTA fibrosis score associations with progression-free survival in IPF. The investigators will perform a cross-sectional analysis of PFF-PR cases comparing quantitative CT and radiomic markers at baseline with and without "at risk" genotypes for association with severity and progression (decline in FVC over time). This will ascertain what markers improve performance of the DTA fibrosis extent scores using Cox regression analysis and accuracy metrics from Aim 1. Findings will be replicated in UVA/Chicago cohort and in the prospective PRECISIONS cohort. This aim will establish the additive value of genetic markers.
Aim 3: The investigators will assess whether DTA and radiomic markers are additive/synergistic with plasma protein and blood transcriptome markers for disease progression. The investigators hypothesize that selected protein and transcriptomic markers will prove additive to DTA fibrosis extent for prediction of progression-free survival whereas other markers correlated with DTA will not. The investigators have chosen published markers from a 4-protein panel signature, along with CCL18, as examples, given their current level of replication and promise. The investigators will also include a 25-gene FVC predictor for disease progression. Similar analyses, as outlined in Aims 1 and 2, will determine their additive information value.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| University of Chicago | – | Diagnostic Test: HRCT, Diagnostic Test: Blood DrawThis cohort will have prior consent to the Natural History of Interstitial Lung Disease, which is an ongoing, longitudinal cohort of patients with clinically diagnosed ILD, including IPF. Patients are recruited from University of Chicago Interstitial Lung Disease Program during their clinic visit. Blood, plasma, and serum samples are collected upon enrollment and stored in a biorepository at University of Chicago. Subsets of patients have repeat blood draw at return clinic visits for specific research studies. The investigators propose collection of 1-year HRCTs, FVC, and DLCO. |
| University of Virginia | – | Diagnostic Test: HRCT, Diagnostic Test: Blood DrawThis cohort will have prior consent to the Natural History of Interstitial Lung Disease, which is an ongoing, longitudinal cohort of patients with clinically diagnosed ILD, including IPF. Patients are recruited from the UVA Interstitial Lung Disease Program during their clinic visit. Blood, plasma, and serum samples are collected upon enrollment and stored in a biorepository at UVA (Pinn Hall RM#2232B, IRB#20937). Subsets of patients have repeat blood draw at return clinic visits for specific research studies. The investigators propose collection of 1-year HRCTs, FVC, and DLCO. |
Who may qualify
- Ages
- 40 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with Pulmonary Fibrosis as described above in inclusion criteria.
Key inclusion criteria (3 listed)
- ≥ 40 years of age
- Diagnosed with IPF according to 2018 ATS/ERS/JRS/ALAT confirmed by the enrolling investigator
- Signed informed consent
Key exclusion criteria (5 listed)
- Pregnancy or planning to become pregnant
- Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year during study participation*
- Significant medical, surgical or psychiatric illness that in the opinion of the investigator would affect subject safety or potential to complete the research study
- Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
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 |
|---|---|---|
| HRCTHigh resolution computed tomography (HRCT) scan is a medical imaging technique used to obtain detailed internal images of the body. HRCT images will be obtained at 0 and 12 months. | Diagnostic test | University of Chicago, University of Virginia |
| Blood DrawDuring blood draw, someone uses a needle to take blood from a vein, usually in your arm. | Diagnostic test | University of Chicago, University of Virginia |
Primary outcome
Derivation of DTA in IPF only cases from the PFF-PR and its associations with disease severity and outcomes.
Time frame: 12 months
Driven texture analysis (DTA) is a machine learning method capable of automatic detection and quantification of lung fibrosis on HRCT. It is trained to discriminate fibrosis using radiologist-identified image regions demonstrating normal lung parenchyma and usual interstitial pneumonia patterns. Changes in Forced Vital Capacity (FVC) measured in liters, reflect increased elastic recoil caused by fibrosis. We will use linear-mixed effects models with random intercept to examine associations of repeated DTA-fibrosis scores with repeated percent predicted FVC measurements over time (12 months minimum). This approach will provide a more precise estimate, power, and account for baseline FVC at an individual level which has implications of how rapid a decline we anticipate. This is the most common approach to examine longitudinal changes of FVC in IPF studies. FVC decline greater than 10% has been shown to be prognostic of worse survival and is a common endpoint in IPF clinical trials.
Determine whether known IPF-risk genetic variants are associated with DTA score.
Time frame: 12 months
This is a cross-sectional analysis to determine whether genetic variants that confer higher risk of disease and progression are associated with higher DTA scores from CT.
Identify novel genetic variants that associate with DTA score progression.
Time frame: 12 months
Determine novel genetic variants that indicate higher risk of disease progression and are associated with higher DTA scores.
Determine if DTA or any constituent radiomic features correlate with select plasma proteins.
Time frame: 12 months
MMP-7, CA-125, YKL, OPN, CCL18 are plasma proteins that have been shown to be associated with risk and prognosis in IPF.
Determine if DTA or any of constituent radiomic features correlate with transcriptomic
Time frame: 12 months
We have previously published a transcriptomic classifier that is predictive of FVC decline in IPF.
Determine the best combination of markers (DTA, proteins and transcriptome) for machine learning algorithms for AUC evaluation of ROCs on all 3 cohorts.
Time frame: 12 months
12-month FVC decline is a validated marker of disease progression in IPF as it's predictive of worse mortality. Receiver operating characteristic curve (ROC) is an analytical method, represented as a graph, that is used to evaluate the performance of a binary diagnostic classification method. The diagnostic test results need to be classified into one of the clearly defined dichotomous categories, such as the presence or absence of a disease. Area under the ROC curve (AUC) measures the entire two-dimensional area underneath the entire ROC curve.
2 secondary outcomes
Determine associations of changes in DTA scores with 12-month changes in FVC and DLCO.
Time frame: 12 months
Determine associations of changes in DTA scores with drug treatment (i.e., antifibrotics)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2024.
- Background: PubMed 29742380Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018 May 10;378(19):1811-1823. doi: 10.1056/NEJMra1705751. No abstract available.
- Background: PubMed 22586007Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, King TE Jr, Collard HR. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012 May 15;156(10):684-91. doi: 10.7326/0003-4819-156-10-201205150-00004.
- Background: PubMed 36514019Podolanczuk AJ, Kim JS, Cooper CB, Lasky JA, Murray S, Oldham JM, Raghu G, Flaherty KR, Spino C, Noth I, Martinez FJ; PRECISIONS Study Team. Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial. BMC Pulm Med. 2022 Dec 13;22(1):475. doi: 10.1186/s12890-022-02281-8.
- Background: PubMed 30139770Humphries SM, Swigris JJ, Brown KK, Strand M, Gong Q, Sundy JS, Raghu G, Schwarz MI, Flaherty KR, Sood R, O'Riordan TG, Lynch DA. Quantitative high-resolution computed tomography fibrosis score: performance characteristics in idiopathic pulmonary fibrosis. Eur Respir J. 2018 Sep 17;52(3):1801384. doi: 10.1183/13993003.01384-2018. Print 2018 Sep.
- Background: PubMed 28493789Humphries SM, Yagihashi K, Huckleberry J, Rho BH, Schroeder JD, Strand M, Schwarz MI, Flaherty KR, Kazerooni EA, van Beek EJR, Lynch DA. Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of Fibrosis at Baseline and 15-Month Follow-up. Radiology. 2017 Oct;285(1):270-278. doi: 10.1148/radiol.2017161177. Epub 2017 May 10.
- Background: PubMed 24836312King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18.
- Background: PubMed 24836310Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82. doi: 10.1056/NEJMoa1402584. Epub 2014 May 18.
- Background: PubMed 26714746Reichmann WM, Yu YF, Macaulay D, Wu EQ, Nathan SD. Change in forced vital capacity and associated subsequent outcomes in patients with newly diagnosed idiopathic pulmonary fibrosis. BMC Pulm Med. 2015 Dec 29;15:167. doi: 10.1186/s12890-015-0161-5.
- Background: PubMed 24231810Schmidt SL, Tayob N, Han MK, Zappala C, Kervitsky D, Murray S, Wells AU, Brown KK, Martinez FJ, Flaherty KR. Predicting pulmonary fibrosis disease course from past trends in pulmonary function. Chest. 2014 Mar 1;145(3):579-585. doi: 10.1378/chest.13-0844.
- Background: PubMed 28388260Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.
- Individual participant dataSharing planned: No. Plan to share de-identified dicom images with Ambrahealth for CT analysis
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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.
Diana Hsu, MA contact
Noth Imre, MD principal investigator
Division of Pulmonary and Critical Care
John Kim principal investigator
Division of Pulmonary and Critical Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Idiopathic Pulmonary Fibrosis, run by University of Virginia 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 3 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 16 Aug 2024. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roselove Nunoo-Asare (4342436074, rnn3b@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Derivation of DTA in IPF only cases from the PFF-PR and its associations with disease severity and outcomes. (time frame: 12 months). The study lists 6 primary outcomes in all. 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 NCT06323876, which also lists 10 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 16 Aug 2024.