PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT
- Conditions
- Interstitial Lung Disease
- Interventions
- Diagnostic Test: HRCT ThoraxDiagnostic Test: Blood biomarkersDevice: Glycocheck Endothelial Glycocalyx AssessmentDiagnostic Test: Peripheral leucocyte telomere lengthDiagnostic Test: Pulmonary function testingDiagnostic Test: Patient reported outcome measures
- Registration Number
- NCT05609201
- Lead Sponsor
- University of Exeter
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 54
- 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
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Healthy Control Blood biomarkers 5 Age, sex and ethnicity matched controls Healthy Control Peripheral leucocyte telomere length 5 Age, sex and ethnicity matched controls Cases Blood biomarkers 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD Cases Pulmonary function testing 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD Cases HRCT Thorax 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD Cases Peripheral leucocyte telomere length 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD Cases Glycocheck Endothelial Glycocalyx Assessment 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD Cases Patient reported outcome measures 36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD Healthy Control Glycocheck Endothelial Glycocalyx Assessment 5 Age, sex and ethnicity matched controls
- Primary Outcome Measures
Name Time Method Prediction of disease progression using multi-modal assessment 12 months Correlation of disease progression status (progressor vs non-progressor) with baseline markers including:
1. Endothelial glycocalyx health via GlycoCheckTM and blood biomarkers
2. qCT metrics
3. Peripheral leucocyte telomere length measured via HT-STELAEndothelial glycocalyx 12 months III. Comparison of endothelial glycocalyx health between healthy controls and participants with fibrotic interstitial lung disease
Feasibility of using qCT for disease prognostication and monitoring 12 months Recruitment, consent and attrition rates and dropout reasons
- Secondary Outcome Measures
Name Time Method Exploratory mechanisms 12 months Exploratory analysis of the data to infer causal mechanisms of disease progression
Longitudinal disease progression 12 months Correlation of longitudinal change of pulmonary function testing:
1. Endothelial glycocalyx health via GlycoCheckTM and blood biomarkers
2. qCT metrics
3. Peripheral leucocyte telomere length measured via HT-STELAPrediction of disease progression 12 months III. Exploratory analysis of the ability of 6 month qCT and PFT change to predict progression at 12 months
Trial Locations
- Locations (1)
University of Exeter Medical School
🇬🇧Exeter, United Kingdom