PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT

Study Overview
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Brief Summary
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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.

Official Title
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PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT

Conditions
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Interstitial Lung Disease

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |