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The Infective Pulmonary Exacerbations in Cystic Fibrosis - an Ecological Perspective

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Andrew Jones, Imperial College London
ClinicalTrials.gov Identifier:
NCT01306279
First received: February 28, 2011
Last updated: March 25, 2013
Last verified: March 2013
History of Changes
  Purpose

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.

  1. Bacterial biodiversity and its clinical significance
  2. The role of bacteria which are able to rapidly mutate (hypermutators)
  3. 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.


Condition
Cystic Fibrosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Infective Pulmonary Exacerbations in Cystic Fibrosis - an Ecological Perspective

Resource links provided by NLM:

MedlinePlus related topics: Cystic Fibrosis
U.S. FDA Resources

Further study details as provided by Imperial College London:

Biospecimen Retention:   Samples Without DNA

Sputum


Estimated Enrollment: 50
Study Start Date: February 2011
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Cystic Fibrosis, infection
Cystic Fibrosis patients with an infective exacerbation

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:

  1. Routine microbiology
  2. Bacterial diversity using 16s RNA identification techniques
  3. Relative abundance of P.aeruginosa hypermutators
  4. 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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult patients with Cystic Fibrosis attending to commence intravenous antibiotics for a pulmonary exacerbation of CF

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01306279

Locations
United Kingdom
Department of Cystic Fibrosis, NHLI, Imperial College,
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Margaret Hodson, MD MSc FRCP Imperial College London
  More Information

No publications provided

Responsible Party: Andrew Jones, Clinical Research Fellow, Imperial College London
ClinicalTrials.gov Identifier: NCT01306279     History of Changes
Other Study ID Numbers: 11/H0713/7
Study First Received: February 28, 2011
Last Updated: March 25, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Cystic Fibrosis
Infection
Pulmonary exacerbation
 Hypermutators
Bacterial diversity
Quorum sensing

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
 Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 16, 2013