Integrated Radiographic and Metabolomics Risk Assessment in Patients With Interstitial Lung Diseases (IRM-ILD)

The purpose of this study is to find out if combining a state-of-the-art form imaging modality with metabolomics in different types of Interstitial Lung Diseases (ILD) patients compared to controls with chronic obstructive pulmonary disorder (COPD)/emphysema and healthy controls will be a better predictor of disease progression. ILD's are a group of chronic, progressive lung diseases. The most common ILD is idiopathic pulmonary fibrosis (IPF). Metabolomics provides a "snapshot" in time of all metabolites present in a biological sample. The imaging procedure should take approximately 20 minutes. All study related collections of samples will be done in a single visit if possible. There are no direct benefits to participants. This is not a treatment study.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Fibrosis; Lung Diseases, Interstitial
• Intervention / Treatment: Device: CT-V; Other: Metabolites

Detailed Description

Interstitial lung diseases (ILD) are a group of chronic, progressive lung disorders. The most common ILD is idiopathic pulmonary fibrosis (IPF) with an average survival ranging between 2.5-5 years after diagnosis. The term pulmonary fibrosis means scarring of the lung tissue and is the cause of worsening shortness of breath. IPF can frequently affect the tissue between the air sacs in the lung called the interstitium and many other areas in lung (blood vessels and air passage ways). Earlier diagnosis of ILD is a prerequisite for better long-term outcomes. However, disease detection and assessment of progression are reliant on many varying host and environmental influences. As a result, patients with ILD are often misdiagnosed early in the disease process. Moreover, patients diagnosed with ILD have different disease courses and predicting which patient is at risk of progression is a challenging problem. Many personalized medicine approaches are being developed but there is a lack of available biomarkers in clinical practice. Biomarkers comes from a new experimental technique called metabolomics which is becoming widely used in medicine and biology for studying living organisms. The method measures the levels of large numbers of naturally occurring small molecules (called metabolites) that are present in the blood, saliva, breath and tissues. The pattern, or fingerprint, of metabolites in human samples can be used to learn about the health of an organism and perhaps allow physicians to diagnose, treat, and follow the progress of specific diseases. Clinical and functional models lack predictive ability to detect patients at risk of disease progression. Thus, there is an urgent need to develop accurate prediction models for disease diagnosis and assess treatment effects.

CT-derived ventilation (CT-V) imaging includes quantitative lung function imaging and lung compliance imaging. CT-V is a newer image processing based technique that uses mathematical modeling and scientific computing to gather changes in lung tissue volumes during the breathing cycle. Beaumont is currently using CT-V for radiotherapy planning. CT-V produces a full 3D map of ventilation/breathing, has better image resolution, provides pertinent measurable imaging information, and does not require a contrast agent. Thus, high-resolution anatomical and functional information can be derived using CT-V.

To better understand the functional and radiographic changes seen in patients with ILD, there is a need to further examine the downstream changes occurring at the level of proteins and metabolites. Metabolomics provides a "snapshot" in time of all metabolites present in a biological sample. Proteins alone or integrated with other systems, is a particularly informative tool for understanding disease biology in ILD patients.Using an untargeted metabolomics platform and profiling serum and breathe from the patients will determine if additional or more robust biomarkers of disease can be identified and, in conjunction with the assessment of regional ventilation differences through CT-V, will provide a better insight into disease process and further help with accurate prognostication.

Participants who have consented for the study and have meet all the inclusion criteria and none of the exclusion criteria will have one full inspiration and expiration CT, and two 4D-CT scans under two different pressures (5 and 10 cm water), except for healthy volunteers. They will have their breath profiled using Owlstone platform and serum collected for metabolomics testing within one week period. Participants will be asked to refrain from smoking one day prior to the study date. All study related sampling will be done in a single visit if possible and if not possible all study procedures and samples will be collected within a one week period.

Disease progression will be assessed using chart review over the next 24 months to assess standard of care pulmonary function evaluation and corresponding CT features respiratory hospitalizations and mortality.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

• Study Contact: Name: Bobbie Lewis, BSN; Phone Number: 248-551-5958; Email: Bobbie.Lewis@beaumont.org

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Pulmonary outpatient clinic and interstitial lung disease clinic at Beaumont Hospital, Royal Oak

Description

Inclusion Criteria:

• Patients greater than 18 years of age
• Patients with a PFT-Pulmonary function test </=3 month plus seven days
• Patients with idiopathic pulmonary fibrosis (IPF), or
• Patients with interstitial lung disease (ILD) other than IPF, or
• Patients with chronic obstructive pulmonary disease COPD/emphysema based on Principal's Investigator's assessment/review, or
• Control subject, someone without a diagnosis of above and deemed and "healthy control" by the PI.

COPD/emphysema and control subjects will be age matched +/-10 years to the ILD subjects.

Exclusion Criteria:

• Patients less than 18 years of age
• Patients with active malignancy in past one year, except for basal and squamous cell skin cancer
• Patients without a PFT-Pulmonary function test </=3 month plus seven days
• Pregnant females
• Cognitive impairment and unable to follow directions, per PI discretion

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Interstitial Lung Disease (ILD); CT-V and metabolite analysis of breath and serum at baseline	Device: CT-V; CT-V is a newer computed tomography scan which is more comprehensive and tracks movement of the lungs.; Other Names: Quantitative lung function imaging and lung compliance imaging; Other: Metabolites; Metabolites are compounds which can be measured in biospecimens and may indicate a disease or biological process.
COPD/Emphysema: Age-matched control; CT-V and metabolite analysis of breath and serum at baseline	Device: CT-V; CT-V is a newer computed tomography scan which is more comprehensive and tracks movement of the lungs.; Other Names: Quantitative lung function imaging and lung compliance imaging; Other: Metabolites; Metabolites are compounds which can be measured in biospecimens and may indicate a disease or biological process.
Healthy Volunteers: Age-matched + /- 10 yrs controls; Metabolite analysis of breath and serum at baseline	Other: Metabolites; Metabolites are compounds which can be measured in biospecimens and may indicate a disease or biological process.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative image lung function	CT-V scores between inhalation and exhalation will be calculated at a voxel level on each lung using the "Integrated Jacobian Formulation" (IJV) CT-V method in patients with IPF, non-IPF ILD and COPD/emphysema patients. Several factors, including the volume of identified "cold spots" (areas with decreased ventilation), total ventilation (the integral of CT-V image over the whole lung), and texture analytics (local means, variances, etc.) will be used to define a CT-V pulmonary function metric. This measure is reported in liters with lower numbers indicating reduced lung function.	baseline
Forced Vital Capacity baseline	Maximum volume exhaled in liters measured on a spirometer at baseline	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Untargeted Metabolic profile of breath	Identity and mean relative concentration of the most discriminating 10 volatile organic compounds identified by Owlstone untargeted metabolomic analysis, using mass spectrometry coupled with liquid and/or gas chromatography and robust bioinformatics, and normalized to controls. A value greater than one indicates increased concentration of the compound, and a value less than one indicates decreased concentration of the compound relative to the concentration in controls.	baseline
Untargeted Metabolic profile of Serum	Identity and mean relative concentration of the most discriminating 10 compounds identified by untargeted metabolomic analysis of serum using mass spectrometry coupled with liquid and/or gas chromatography and robust bioinformatics and normalized to controls. A value greater than one indicates increased concentration of the compound, and a value less than one indicates decreased concentration of the compound relative to the concentration in controls.	baseline

Collaborators and Investigators

• Sponsor: William Beaumont Hospitals
• Investigators: Principal Investigator: Girish B Nair, MD, William Beaumont Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): October 20, 2022
• Study Completion (Actual): October 20, 2022

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: metabolomics; lung disease; precision medicine; pulmonary fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: 2019-241

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: No
• product manufactured in and exported from the U.S.: No