The Coagulation Cascade in Idiopathic Pulmonary Fibrosis

NCT02885961 | Unknown

• 1 other identifier: IRAS191454
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is incompletely understood but recurrent epithelial injury occurs which evokes the coagulation cascade. Thrombin is produced as a result and is over expressed in IPF patients, so may be important in propagating disease activity. We aim to recruit patients with IPF and then complete FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) PET (positron emission tomography) scans pre and post manipulation of the coagulation cascade to assess the role of this biological pathway in disease activity. Previous studies from our institution have demonstrated increased FDG avidity in the lungs of patients with IPF (assessed using FDG PET scans) but to date the cells and pathways responsible for this signal have not been identified and thus need further exploration.

Conditions

Idiopathic Pulmonary Fibrosis; IPF; Interstitial Lung Disease

Outcome Measures

Primary Outcomes (1)

• Demonstrate a change in FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) avidity

  FDG avidity describes the degree of tissue uptake of the labelled glucose. It is a numerical continuous variable. It is calculated from the scan using several methods, manually on a workstation and using a mathematical modelling computer programme. The main number generated is called the standardised uptake value (SUV) and the higher the number the higher the metabolic activity in the area. The degree of activity will be quantified for each individual and compared with standard measures of disease activity i.e. lung function measures and quality of life questionnaires. For each individual the change in the SUV measure will be analysed from the scan performed before and then after manipulation of the coagulation cascade.

  Approximately 4 weeks

Secondary Outcomes (1)

• Demonstrate changes in various coagulation factors

  Approximately 4 weeks

Study Arms (1)

Dabigatran

OTHER

All patients will be entered into the arm, i.e. this is a single arm study. All patients will complete 2 FDG PET scans. All patients will receive dabigatran (direct thrombin inhibitor) at a dose of 110mg twice daily (oral). The drug will be given for 24 days (+/-3 days). The variation in duration reflects that scans are completed Monday to Friday only.

Drug: Dabigatran; Radiation: FDG PET scan

Interventions

Dabigatran DRUG

Anti-coagulant

Dabigatran

FDG PET scan RADIATION

Scan using PET combined with a high resolution CT scan (HRCT)

Dabigatran

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of IPF based on multi disciplinary meeting discussion following review of the clinical history, characteristic features on HRCT (high resolution CT scan) and/or usual interstitial pneumonia (UIP) histology.
• Written informed consent obtained from subject.

You may not qualify if:

• Age \<40 or \>80 years
• Renal impairment as defined by a creatinine clearance of \<30 millilitres/min
• Significant liver impairment with evidence of synthetic dysfunction
• Any contraindication to anti-coagulation including previous life threatening or serious bleed or bleeding tendency.
• Co-administration of any concomitant medications prohibited in full protocol. N-acetyl cysteine, prednisolone up to 10mg daily and pirfenidone are permitted.
• Pregnant, breast feeding or unwilling to practice birth control during participation in the study (females of child bearing age).
• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient of the quality of the data.

Sponsors & Collaborators

• University College, London: lead

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Joanna C Porter, PhD FRCP

  University College, London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joanna C Porter, PhD FRCP

CONTACT

02076796972; joanna.porter@ucl.ac.uk

Helen S Garthwaite, MB BS MRCP

CONTACT

07980690756; helen.garthwaite@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: September 1, 2016
• Study Start: August 1, 2016
• Primary Completion: August 1, 2017
• Last Updated: September 1, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share