The Coagulation Cascade in Idiopathic Pulmonary Fibrosis

NCT ID: NCT02885961

Last Updated: 2016-09-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31

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.

Detailed Description

Patients with IPF who meet all the inclusion criteria (and none of the exclusion criteria) will be assessed and invite to participate.

They will undergo baseline assessment with lung function, 6 minute walk test and health quality assessments.

Blood tests will assess the pro-coagulant state of these individuals. They will undergo a baseline FDG PET scan followed by manipulation of the coagulation cascade with 24 days (+/- 3 days) dabigatran. They will then complete a second FDG PET, health quality assessments and blood tests to demonstrate target engagement.

Conditions

Idiopathic Pulmonary Fibrosis; IPF; Interstitial Lung Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Dabigatran

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.

Group Type: OTHER

Dabigatran

Intervention Type: DRUG

Anti-coagulant

FDG PET scan

Intervention Type: RADIATION

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

Interventions

Dabigatran

Anti-coagulant

Intervention Type: DRUG

FDG PET scan

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

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joanna C Porter, PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

University College, London

Central Contacts

Joanna C Porter, PhD FRCP

Role: CONTACT

joanna.porter@ucl.ac.uk

02076796972

Helen S Garthwaite, MB BS MRCP

Role: CONTACT

helen.garthwaite@nhs.net

07980690756

Other Identifiers

IRAS191454

Identifier Type: -

Identifier Source: org_study_id