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The Coagulation Cascade in Idiopathic Pulmonary Fibrosis

Primary Purpose

Idiopathic Pulmonary Fibrosis, IPF, Interstitial Lung Disease

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Dabigatran
FDG PET scan
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Idiopathic Pulmonary Fibrosis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Other

    Arm Label

    Dabigatran

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Demonstrate changes in various coagulation factors
    This patient group have demonstrated a hyper coagulable state in a number of previous studies. We will demonstrate this using blood tests prior to administration of dabigatran. The coagulation markers (a blood test, many used in standard clinical practice) will be repeated during treatment to demonstrate target engagement.

    Full Information

    First Posted
    August 15, 2016
    Last Updated
    August 26, 2016
    Sponsor
    University College, London
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02885961
    Brief Title
    The Coagulation Cascade in Idiopathic Pulmonary Fibrosis
    Official Title
    Investigating the Role of the Coagulation Cascade in Idiopathic Pulmonary Fibrosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2016
    Overall Recruitment Status
    Unknown status
    Study Start Date
    August 2016 (undefined)
    Primary Completion Date
    August 2017 (Anticipated)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University College, London

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Idiopathic Pulmonary Fibrosis, IPF, Interstitial Lung Disease

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    12 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Dabigatran
    Arm Type
    Other
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Dabigatran
    Intervention Description
    Anti-coagulant
    Intervention Type
    Radiation
    Intervention Name(s)
    FDG PET scan
    Intervention Description
    Scan using PET combined with a high resolution CT scan (HRCT)
    Primary Outcome Measure Information:
    Title
    Demonstrate a change in FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) avidity
    Description
    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.
    Time Frame
    Approximately 4 weeks
    Secondary Outcome Measure Information:
    Title
    Demonstrate changes in various coagulation factors
    Description
    This patient group have demonstrated a hyper coagulable state in a number of previous studies. We will demonstrate this using blood tests prior to administration of dabigatran. The coagulation markers (a blood test, many used in standard clinical practice) will be repeated during treatment to demonstrate target engagement.
    Time Frame
    Approximately 4 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Joanna C Porter, PhD FRCP
    Phone
    02076796972
    Email
    joanna.porter@ucl.ac.uk
    First Name & Middle Initial & Last Name or Official Title & Degree
    Helen S Garthwaite, MB BS MRCP
    Phone
    07980690756
    Email
    helen.garthwaite@nhs.net
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Joanna C Porter, PhD FRCP
    Organizational Affiliation
    University College, London
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    The Coagulation Cascade in Idiopathic Pulmonary Fibrosis

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