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Target Validation and Discovery in Idiopathic Bronchiectasis

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ClinicalTrials.gov Identifier: NCT03750734
Recruitment Status : Not yet recruiting
First Posted : November 22, 2018
Last Update Posted : March 28, 2019
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Papworth Hospital NHS Foundation Trust

Tracking Information
First Submitted Date November 20, 2018
First Posted Date November 22, 2018
Last Update Posted Date March 28, 2019
Estimated Study Start Date May 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 21, 2018)
Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues. [ Time Frame: 2 years ]
Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03750734 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: November 21, 2018)
  • Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells [ Time Frame: 2 years ]
    Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells
  • Functional characterisation of airway epithelium [ Time Frame: 2 years ]
    Functional characterisation of airway epithelium
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Target Validation and Discovery in Idiopathic Bronchiectasis
Official Title Target Validation and Discovery in Idiopathic Bronchiectasis
Brief Summary

Bronchiectasis is a long-term lung condition where the airways become abnormally enlarged, leading to a build-up of mucus and inflammation that makes the lungs more susceptible to recurrent infection. Patients with bronchiectasis have subtle abnormalities in the way their airway cells respond to infection that are, in part, responsible for the development of their condition. At present there are no licensed treatments for bronchiectasis.

This study will aim to characterise in depth some of these abnormalities with a view to future studies that will try to develop treatments that can directly target those abnormalities at a molecular level.

Patients known to have bronchiectasis who have provided written informed consent will be enrolled alongside healthy volunteers and patients with chronic obstructive pulmonary disease and cystic fibrosis, for comparison. Participants will give a blood sample and have a bronchoscopy. This is a thin telescopic tube, passed through the nose or mouth, under sedation, into the airways that will allow a sample of bronchial epithelial cells to be taken.

The main objective of the study is to achieve a greater understanding of some of the key biological processes/pathways and disease marker genes that play a role in the development of bronchiectasis. This is important because, at present, little is known about the underlying disease mechanisms and there are no licensed treatments for bronchiectasis.

The investigator's hope this in-depth characterisation of specific bronchial epithelial cell abnormalities in bronchiectasis will shed light on novel targets for future drug discovery.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Whole blood, bronchial biopsy, bronchial brushings, bronchoalveolar lavage
Sampling Method Non-Probability Sample
Study Population Secondary care respiratory clinics
Condition
  • Bronchiectasis
  • Idiopathic Bronchiectasis
Intervention
  • Diagnostic Test: Bronchoscopy
    Flexible bronchoscopy will be performed under sedation (typically a sedative such as intravenous midazolam and/or fentanyl) with local anaesthetic to the throat and vocal cords. Bronchial epithelial tissue (via bronchial brushing and biopsy forceps) and bronchial lavage samples will be taken for analysis.
  • Diagnostic Test: Blood test
    Peripheral blood will be taken to collect peripheral blood monocytes, which will then allow the production of induced pluripotent stem cell derived bronchial epithelial tissues.
Study Groups/Cohorts
  • Idiopathic bronchiectasis
    Idiopathic bronchiectasis participants
    Interventions:
    • Diagnostic Test: Bronchoscopy
    • Diagnostic Test: Blood test
  • COPD
    Chronic obstructive pulmonary disease participants
    Interventions:
    • Diagnostic Test: Bronchoscopy
    • Diagnostic Test: Blood test
  • Cystic fibrosis
    Cystic fibrosis participants
    Interventions:
    • Diagnostic Test: Bronchoscopy
    • Diagnostic Test: Blood test
  • Healthy volunteers
    Healthy volunteers
    Interventions:
    • Diagnostic Test: Bronchoscopy
    • Diagnostic Test: Blood test
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: November 21, 2018)
50
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

Bronchiectasis participants

  1. Confirmed HRCT diagnosis of bronchiectasis in more than 1 lobe
  2. Bronchiectasis not attributable to another cause, e.g. cystic fibrosis/ABPA/PCD
  3. Absence of significant emphysema, COPD or asthma
  4. Have provided written informed consent that they are willing to participate in the study prior to sample collection

COPD participants (disease controls)

  1. Confirmed diagnosis of COPD according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria (FEV1/FVC ratio < 0.70)
  2. Absence of significant bronchiectasis on HRCT
  3. Have provided written informed consent that they are willing to participate in the study prior to sample collection

Cystic fibrosis participants (disease controls)

  1. Have a confirmed diagnosis of cystic fibrosis
  2. Have provided written informed consent that they are willing to participate in the study prior to sample collection

Healthy controls

  1. No history or diagnosis of clinically significant lung disease
  2. Be a non-smoker for > 1 year at screening and have < 5 pack year history of smoking
  3. Have provided written informed consent that they are willing to participate in the study prior to sample collection

Exclusion Criteria:

  1. Any clinically significant acute illness, including recent exacerbation of lung disease requiring treatment with oral or intravenous antibiotics, in 6 weeks prior to screening
  2. Any contraindication to safe bronchoscopy as judged by CI or clinical team (FEV1 < 30% predicted, oxygen saturations < 92% on room air etc.)
  3. Any clinically significant bleeding disorder or use of anticoagulant/antiplatelet therapy that could place participants at risk of bleeding
  4. Any contraindication to sedation or local anaesthetic medications used for bronchoscopy
  5. Current smoking within 6 months prior to screening (defined as someone who has smoked at least one cigarette per day (or pipe, cigar, or cannabis) for ≥ 30 days within 6 months prior to screening)
  6. Acute MI, acute stroke or major surgery within 6 months prior to screening
  7. History of uncontrolled ischaemic heart disease that place participants at risk during bronchoscopy
  8. History of ventilatory failure or hypercapnia that may complicate bronchoscopy
  9. Any known active tuberculous or non-tuberculous mycobacterial infection
  10. Any use of oral corticosteroids within 4 weeks of screening
  11. Any systemic immunomodulatory or immunosuppressive therapy within 3 months of screening
  12. Known current malignancy or current evaluation for a potential malignancy
  13. Any other clinically significant medical disease that is uncontrolled despite treatment, that is likely, in the opinion of the investigators, to impact the patient's ability to safely participate in the study
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Listed Location Countries Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number NCT03750734
Other Study ID Numbers P02437
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Papworth Hospital NHS Foundation Trust
Study Sponsor Papworth Hospital NHS Foundation Trust
Collaborators GlaxoSmithKline
Investigators Not Provided
PRS Account Papworth Hospital NHS Foundation Trust
Verification Date March 2019