- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01306279
The Infective Pulmonary Exacerbations in Cystic Fibrosis - an Ecological Perspective
Given the treatment burden and excess morbidity and mortality associated with acute infective exacerbations in cystic fibrosis, a clear understanding of the mechanisms involved in the origins of an infective exacerbation and the response to antibiotics is vital to improving long-term outcomes in CF.
This study will examine 3 areas of interest in CF exacerbations.
- Bacterial biodiversity and its clinical significance
- The role of bacteria which are able to rapidly mutate (hypermutators)
- Inter-bacterial communication and its role in infective exacerbations
Study Hypothesis 1
Increased microbiological diversity represents a balanced community of bacteria. The presence of a diverse population of bacteria in CF infections therefore predicts a better outcome for treatment than when a population consists of a small number of more virulent organisms.
Study Hypothesis 2
Pseudomonas aeruginosa hypermutators can mutate much more often than ordinary Pseudomonas aeruginosa bacteria. Hypermutators are likely to grow better when the bacteria are under stress, such as during antibiotic treatment or during an infection. They are, however, weaker organisms because of the multiple mutations they have undergone. Their presence does not relate to clinical outcome but may be associated with the emergence of antibiotic resistance.
Study Hypothesis 3
Some Pseudomonas aeruginosa bacteria communicate with each other by secreting and responding to chemicals known as quorum sensing (QS)molecules. As well as affecting the behaviour of bacteria, these QS molecules can cause inflammation in the lung of CF patients. Selective growth of QS-producing organisms can trigger lung exacerbations in CF. If antibiotics kill this population of bacteria and QS molecule levels drop in the lung, patients recover from infection quickly. Failure to kill these bacteria with antibiotics allow QS molecule levels to remain elevated and patients to have prolonged infections.
Study Overview
Status
Conditions
Detailed Description
We will sequentially recruit patients attending our CF centre with an infective exacerbation of CF, who are chronically infected with Pseudomonas aeruginosa.
We will record spirometry, blood markers of inflammation, quality of life questionnaires and investigate sputum samples for:
- Routine microbiology
- Bacterial diversity using 16s RNA identification techniques
- Relative abundance of P.aeruginosa hypermutators
- Levels of quorum sensing molecules
These observations will be undertaken before commencing intravenous antibiotic therapy, on days 7, 10 and the last day of antibiotic therapy. Patients will also be reviewed one month after the end of antibiotic therapy where spirometry and a sputum sample will be collected for the above investigations.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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London, United Kingdom, SW3 6NP
- Department of Cystic Fibrosis, NHLI, Imperial College,
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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:
- Confirmed diagnosis of Cystic Fibrosis
- Chronic Pseudomonas aeruginosa
- Symptoms and signs of infective exacerbation
Exclusion Criteria:
- age under 16
- unable to give consent or patients with significant mental health problems
- co-existent active allergic bronchopulmonary aspergillosis requiring a change in steroid or antifungal therapy
- a previous participant in this study
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Cystic Fibrosis, infection
Cystic Fibrosis patients with an infective exacerbation
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Margaret Hodson, MD MSc FRCP, Imperial College London
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 11/H0713/7
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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