PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT

NCT05609201 | Enrolling By Invitation DMC

• 1 other identifier: 2021-22-54
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Interstitial Lung Disease

Outcome Measures

Primary Outcomes (3)

• Prediction of disease progression using multi-modal assessment

  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-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 Outcomes (3)

• Longitudinal disease progression

  12 months

• Exploratory mechanisms

  12 months

• Prediction of disease progression

  12 months

Study Arms (2)

Cases

36 participants with a multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD

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

Healthy Control

5 Age, sex and ethnicity matched controls

Device: Glycocheck Endothelial Glycocalyx Assessment; Diagnostic Test: Blood biomarkers; Diagnostic Test: Peripheral leucocyte telomere length

Interventions

HRCT Thorax DIAGNOSTIC_TEST

HRCT Thorax at 0, 6 and 12 months

Cases

Glycocheck Endothelial Glycocalyx Assessment DEVICE

Measure of EG degradation using GlycoCheck Microvascular Health Score at 0, 6 and 12 months

Cases; Healthy Control

Blood biomarkers DIAGNOSTIC_TEST

Endothelial glycocalyx degradation blood biomarkers and angiogenesis markers at 0, 6 and 12 months

Cases; Healthy Control

Peripheral leucocyte telomere length DIAGNOSTIC_TEST

HT-STELA (High-throughput single telomere length assessment) at 0, 6 and 12 months

Cases; Healthy Control

Pulmonary function testing DIAGNOSTIC_TEST

Pulmonary Function Tests (Spirometry and Gas Transfer) and 6-minute walk distance at 0, 6 and 12 months

Cases

Patient reported outcome measures DIAGNOSTIC_TEST

Electronic collection of patient reported outcome measures

Cases

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Exeter: lead
• North Bristol NHS Trust: collaborator
• Royal United Hospitals Bath NHS Foundation Trust: collaborator
• Royal Devon and Exeter NHS Foundation Trust: collaborator

Study Sites (1)

University of Exeter Medical School

Exeter, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Each time point the following blood samples will be required: 1. 5ml EDTA for FBC 2. 5ml SST for CRP 3. 10ml EDTA for plasma, buffy coat and red blood cell layers for study of peripheral leucocyte telomere length and ELISA for endothelial glycocalyx and angiogenesis markers 4. 10ml EDTA and 10ml Plasma for stored sample for future ancillary research

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Respiratory Function Tests

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Giles Dixon

  University of Exeter

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 8, 2022
• Study Start: June 1, 2023
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• 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.

Locations

GB (1)