Clinical trial NCT02885961: The Coagulation Cascade in Idiopathic Pulmonary Fibrosis
Official title: Investigating the Role of the Coagulation Cascade in Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Idiopathic Pulmonary Fibrosis
IPF
Interstitial Lung Disease
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2016-09-01
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Demonstrate a change in FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) avidity
timeFrame: Approximately 4 weeks
Secondary outcomes:
measure: Demonstrate changes in various coagulation factors
timeFrame: Approximately 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: University College, London
name: Joanna C Porter, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References: