- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03750734
Target Validation and Discovery in Idiopathic Bronchiectasis
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Cambridge, United Kingdom
- Royal Papworth Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Bronchiectasis participants
- Confirmed HRCT diagnosis of bronchiectasis in more than 1 lobe
- Bronchiectasis not attributable to another cause, e.g. cystic fibrosis/ABPA/PCD
- Absence of significant emphysema, COPD or asthma
- Have provided written informed consent that they are willing to participate in the study prior to sample collection
COPD participants (disease controls)
- Confirmed diagnosis of COPD according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria (FEV1/FVC ratio < 0.70)
- Absence of significant bronchiectasis on HRCT
- Have provided written informed consent that they are willing to participate in the study prior to sample collection
Cystic fibrosis participants (disease controls)
- Have a confirmed diagnosis of cystic fibrosis
- Have provided written informed consent that they are willing to participate in the study prior to sample collection
Healthy controls
- No history or diagnosis of clinically significant lung disease
- Be a non-smoker for > 1 year at screening and have < 5 pack year history of smoking
- Have provided written informed consent that they are willing to participate in the study prior to sample collection
Exclusion Criteria:
- Any clinically significant acute illness, including recent exacerbation of lung disease requiring treatment with oral or intravenous antibiotics, in 6 weeks prior to screening
- Any contraindication to safe bronchoscopy as judged by CI or clinical team (FEV1 < 30% predicted, oxygen saturations < 92% on room air etc.)
- Any clinically significant bleeding disorder or use of anticoagulant/antiplatelet therapy that could place participants at risk of bleeding
- Any contraindication to sedation or local anaesthetic medications used for bronchoscopy
- 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)
- Acute MI, acute stroke or major surgery within 6 months prior to screening
- History of uncontrolled ischaemic heart disease that place participants at risk during bronchoscopy
- History of ventilatory failure or hypercapnia that may complicate bronchoscopy
- Any known active tuberculous or non-tuberculous mycobacterial infection
- Any use of oral corticosteroids within 4 weeks of screening
- Any systemic immunomodulatory or immunosuppressive therapy within 3 months of screening
- Known current malignancy or current evaluation for a potential malignancy
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Healthy volunteers
|
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.
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.
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Idiopathic bronchiectasis
Idiopathic bronchiectasis participants
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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.
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.
Time Frame: 2 years
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Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells
Time Frame: 2 years
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Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells
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2 years
|
Functional characterisation of airway epithelium
Time Frame: 2 years
|
Functional characterisation of airway epithelium
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2 years
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Dr W Flowers, Royal Papworth Hospital
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P02437
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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