PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT (PREDICT-ILD)

The interstitial lung diseases (ILD) are a heterogenous group of conditions with varying degrees of inflammation and scarring (fibrosis) of the lungs. ILD progression is unpredictable, making prognostication challenging. A proportion of patients will develop inexorably progressive disease termed progressive fibrosing ILD (PF-ILD).

Forced vital capacity (FVC), a lung function variable, is routinely used to monitor disease progression. However FVC can be a poor disease marker as it can be influenced by patient effort and can be difficult to perform. High resolution computed tomography (HRCT) is a necessary investigation for suspected fibrotic-ILD, making it a promising tool for research.

A quantitative-CT (qCT) approach uses computer software to analyse HRCT scans and has advantage over visual radiologist assessments which are limited by inter/intra-observer variance. The investigators will undertake a feasibility study to determine whether baseline and longitudinal qCT can predict and quantify disease progression in fibrotic-ILD.

The endothelial glycocalyx (EG) is a mesh-like layer that lines the small blood vessels. Injury to this layer has been implicated in non-thoracic fibrotic diseases. Telomeres are repetitive genetic sequences which cap chromosomes preventing their damage during cell replication. Prematurely shortened leucocyte telomere lengths (LTL) have been demonstrated in a wide range of ILDs. We will evaluate role of measuring EG health and LTL in disease prognostication.

Adult participants with fibrotic-ILD from 3 centres in England will be recruited alongside healthy controls. Case (disease) participants will undergo investigations at 0, 6 and 12 months from recruitment including:

• HRCT with quantitative analysis (qCT)
• Lung function testing
• EG and LTL measurement
• Health related quality of life assessments

The primary outcome will assess the correlation of disease progression status measured by standard of care (FVC) with baseline qCT and EG assessment. Healthy controls will only undergo EG assessment at all time points. Feasibility outcomes will be assessed including recruitment, consent and attrition rates.

The results will inform a subsequent multi-centre study to assess the clinical benefit of disease monitoring with the measures assessed in this study.

Study Overview

• Status: Enrolling by invitation
• Conditions: Interstitial Lung Disease
• Intervention / Treatment: Diagnostic test: HRCT Thorax; Device: Glycocheck Endothelial Glycocalyx Assessment; Diagnostic test: Blood biomarkers; Diagnostic test: Peripheral leucocyte telomere length; Diagnostic test: Pulmonary function testing; Diagnostic test: Patient reported outcome measures

• Study Type: Observational
• Enrollment (Estimated): 54

Contacts and Locations

Study Locations

• United Kingdom
  • Exeter, United Kingdom
    • University of Exeter Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants under the clinical care of the interstitial lung disease teams at the following hospitals:

• Royal University Hospitals Bath NHS Foundation Trust, UK
• Royal Devon University Healthcare, UK
• North Bristol NHS Foundation Trust

Description

Inclusion Criteria:

• Multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD
• Treatment naivety to anti-fibrotic therapy at entry to study
• Adult ≥18 years <85
• Informed consent

Exclusion Criteria:

• Forced expiratory volume in 1s/FVC <0.7,
• Significant other respiratory pathology including emphysema >15% on CT (radiologist determined)
• Evidence of ILD exacerbation at the time of CT

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD	Diagnostic test: HRCT Thorax; HRCT Thorax at 0, 6 and 12 months; Device: Glycocheck Endothelial Glycocalyx Assessment; Measure of EG degradation using GlycoCheck Microvascular Health Score at 0, 6 and 12 months; Diagnostic test: Blood biomarkers; Endothelial glycocalyx degradation blood biomarkers and angiogenesis markers at 0, 6 and 12 months; Diagnostic test: Peripheral leucocyte telomere length; HT-STELA (High-throughput single telomere length assessment) at 0, 6 and 12 months; Diagnostic test: Pulmonary function testing; Pulmonary Function Tests (Spirometry and Gas Transfer) and 6-minute walk distance at 0, 6 and 12 months; Diagnostic test: Patient reported outcome measures; Electronic collection of patient reported outcome measures
Healthy Control; 5 Age, sex and ethnicity matched controls	Device: Glycocheck Endothelial Glycocalyx Assessment; Measure of EG degradation using GlycoCheck Microvascular Health Score at 0, 6 and 12 months; Diagnostic test: Blood biomarkers; Endothelial glycocalyx degradation blood biomarkers and angiogenesis markers at 0, 6 and 12 months; Diagnostic test: Peripheral leucocyte telomere length; HT-STELA (High-throughput single telomere length assessment) at 0, 6 and 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of disease progression using multi-modal assessment	Correlation of disease progression status (progressor vs non-progressor) with baseline markers including: Endothelial glycocalyx health via GlycoCheckTM and blood biomarkers; qCT metrics; Peripheral leucocyte telomere length measured via HT-STELA	12 months
Feasibility of using qCT for disease prognostication and monitoring	Recruitment, consent and attrition rates and dropout reasons	12 months
Endothelial glycocalyx	III. Comparison of endothelial glycocalyx health between healthy controls and participants with fibrotic interstitial lung disease	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal disease progression	Correlation of longitudinal change of pulmonary function testing: Endothelial glycocalyx health via GlycoCheckTM and blood biomarkers; qCT metrics; Peripheral leucocyte telomere length measured via HT-STELA	12 months
Exploratory mechanisms	Exploratory analysis of the data to infer causal mechanisms of disease progression	12 months
Prediction of disease progression	III. Exploratory analysis of the ability of 6 month qCT and PFT change to predict progression at 12 months	12 months

Collaborators and Investigators

• Sponsor: University of Exeter
• Collaborators: North Bristol NHS Trust; Royal Devon and Exeter NHS Foundation Trust; Royal United Hospitals Bath NHS Foundation Trust
• Investigators: Principal Investigator: Giles Dixon, University of Exeter

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Disease Progression; Lung Diseases; Lung Diseases, Interstitial
• Other Study ID Numbers: 2021-22-54

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be available on an anonymised basis via Open Research Exeter data depository (https://ore.exeter.ac.uk/repository).
• IPD Sharing Time Frame: Study protocol will be available at the time of study recruitment Informed consent for will be available at the time of study recruitment. Clinical study report will be published within 12 months of study completion.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No