The Role of Quantitative CT and Radiomic Biomarkers for Precision Medicine in Pulmonary Fibrosis

NCT06323876 | Recruiting

• 2 other identifiers: HSR231590R01HL171918
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

CT; biomarkers; gene expression; radiomic markers

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  12 months

Secondary Outcomes (2)

• Determine associations of changes in DTA scores with 12-month changes in FVC and DLCO.

  12 months

• Determine associations of changes in DTA scores with drug treatment (i.e., antifibrotics)

  12 months

Study Arms (2)

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.

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.

Diagnostic Test: HRCT; Diagnostic Test: Blood Draw

Interventions

HRCT DIAGNOSTIC_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.

University of Chicago; University of Virginia

Blood Draw DIAGNOSTIC_TEST

During blood draw, someone uses a needle to take blood from a vein, usually in your arm.

University of Chicago; University of Virginia

Eligibility Criteria

• Age: 40 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with Pulmonary Fibrosis as described above in inclusion criteria.

You may qualify if:

• ≥ 40 years of age
• Diagnosed with IPF according to 2018 ATS/ERS/JRS/ALAT confirmed by the enrolling investigator
• Signed informed consent

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Virginia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

Related Publications (10)

• 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.

  PMID: 29742380 BACKGROUND

• Ley 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.

  PMID: 22586007 BACKGROUND

• Podolanczuk 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.

  PMID: 36514019 BACKGROUND

• Humphries 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.

  PMID: 30139770 BACKGROUND

• Humphries 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.

  PMID: 28493789 BACKGROUND

• King 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.

  PMID: 24836312 BACKGROUND

• Richeldi 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.

  PMID: 24836310 BACKGROUND

• Reichmann 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.

  PMID: 26714746 BACKGROUND

• Schmidt 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.

  PMID: 24231810 BACKGROUND

• Paterniti 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.

  PMID: 28388260 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimens are blood DNA, RNA, and plasma proteins.

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Noth Imre, MD

  Division of Pulmonary and Critical Care

  PRINCIPAL INVESTIGATOR

• John Kim

  Division of Pulmonary and Critical Care

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roselove Nunoo-Asare

CONTACT

4342436074; rnn3b@uvahealth.org

Diana Hsu, MA

CONTACT

NBR2DF@uvahealth.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department Chair of Pulmonary & Critical Care

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: March 21, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: August 16, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)