PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT

Interstitial Lung Disease Clinical Trial

— PREDICT-ILD  

Official title:

PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05609201
• Other study ID #: 2021-22-54
• Status: Enrolling by invitation
• Start date: June 1, 2023
• Est. completion date: October 31, 2024

Study information

• Verified date: May 2024
• Source: University of Exeter
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 54
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Disease Progression
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial

Intervention

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
• Peripheral leucocyte telomere length
HT-STELA (High-throughput single telomere length assessment) at 0, 6 and 12 months
• Pulmonary function testing
Pulmonary Function Tests (Spirometry and Gas Transfer) and 6-minute walk distance at 0, 6 and 12 months
• Patient reported outcome measures
Electronic collection of patient reported outcome measures

Locations

Country	Name	City	State
United Kingdom	University of Exeter Medical School	Exeter

Sponsors (4)

Lead Sponsor	Collaborator
University of Exeter	North Bristol NHS Trust, Royal Devon and Exeter NHS Foundation Trust, Royal United Hospitals Bath NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Feasibility of using qCT for disease prognostication and monitoring	Recruitment, consent and attrition rates and dropout reasons	12 months
Primary	Endothelial glycocalyx	III. Comparison of endothelial glycocalyx health between healthy controls and participants with fibrotic interstitial lung disease	12 months
Secondary	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
Secondary	Exploratory mechanisms	Exploratory analysis of the data to infer causal mechanisms of disease progression	12 months
Secondary	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