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.
Study Type
Observational
Primary Outcome
Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.
Secondary Outcome
Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells
Condition
Bronchiectasis
Intervention
Bronchoscopy
Study Arms / Comparison Groups
Idiopathic bronchiectasis
Description: Idiopathic bronchiectasis participants
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Diagnostic Test
Estimated Enrollment
50
Start Date
September 10, 2019
Completion Date
January 2022
Primary Completion Date
January 2022
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
Gender
All
Ages
18 Years - 80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Dr W Flowers, 01223638000, [email protected]
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT03750734
Organization ID
P02437
Responsible Party
Sponsor
Study Sponsor
Papworth Hospital NHS Foundation Trust
Collaborators
GlaxoSmithKline
Study Sponsor
Dr W Flowers, Principal Investigator, Royal Papworth Hospital
Verification Date
August 2020