FYI- Bronchiectasis: breaking the cycle of inflammation and infection - Lancet

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The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of BronchiectasisVerified by: The First Affiliated Hospital of Guangzhou Medical University, January 2013
First Received: January 15, 2013 | Last Updated: January 17, 2013
Phase: Phase 4 | Start Date: July 2013
Overall Status: Not yet recruiting | Estimated Enrollment: 60

[h=2]Brief Summary[/h]Skip to Participation Criteria

Official Title: “The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis”
The purpose of this study is to examine the efficacy and safety of 24 weeks treatment with theophylline plus low-dose formoterol-budesonide in subjects with bronchiectasis.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
  • Study Primary Completion Date: June 2014
[h=2]Detailed Clinical Trial Description[/h]Non-cystic fibrosis bronchiectasis is an orphan disease caused by the pathogenic vicious circle including infection, inflammation and airway repair. Today's principle of treatment is to break the cycle of inflammation and infection. Nowadays, most clinical trials are anti-infective treatment by antibiotics trying to break this cycle by reducing the bacterial load, which may cause bacterial resistance. There were still some anti-inflammation trials by using inhaled corticosteroids(ICS). Tsang and Martínez-García showed that inhaled corticosteroids reduced IL-1,IL-8 levels and sputum inflammation cells, and improved sputum volume as well as quality of life, though the corticosteroid must be high dose or medium dose combined with long-acting ß2 adrenergic agonists. As described in asthma and chronic obstructive pulmonary disease(COPD), theophylline can improve the activity of histone deacetylase (HDAC) and then enhanced the anti-inflammatory effect of steroids. We hypothesis that theophylline may have the same effect in subjects with bronchiectasis. Theophylline plus inhaled low-dose formoterol-budesonide may improve quality of life and reduce airway inflammation.
[h=2]Interventions Used in this Clinical Trial[/h]
  • Drug: Formoterol-budesonide
    • Formoterol-budesonide combined treatment (4.5µg/160µg Q12H)
  • Drug: Theophylline
    • Theophylline 0.1 Q12H
  • Drug: Placebo
    • Placebo for theophylline 0.1 Q12H
[h=2]Arms, Groups and Cohorts in this Clinical Trial[/h]
  • Placebo Comparator: Placebo+formoterol-budesonide
    • Placebo(for Theophylline sustained-release tablet) tablet by mouth 100mg every 12hours for 24weeks. Inhaled Formoterol-budesonide combined treatment 4.5µg/160µg every 12hours for 24weeks.
  • Experimental: Theophylline+formoterol-budesonide
    • Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks. Inhaled formoterol-budesonide combined treatment 4.5µg/160µg every 12hours for 24weeks.
[h=2]Outcome Measures for this Clinical Trial[/h][h=3]Primary Measures[/h]
  • Quality of Life Assessment with St George’s Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ)
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
[h=3]Secondary Measures[/h]
  • Mean number of exacerbations per patient per 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of sputum characteristics from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of 24 hour sputum volume from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of mean forced expiratory flow between 25% and 75% of the FVC(FEF25-75)from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of forced vital capacity(FVC) from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of peak expiratory flow(PEF) from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Induced sputum cytology count
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Changes of sputum culture from baseline to 24 weeks
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Interleukin-1ß(IL-1ß)
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • IL-6
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • IL-8
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • IL-10
    • Time Frame: At 24 weeks
      Safety Issue?: No
  • Tumor necrosis factor(TNF)α
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Activity of histone deacetylase(HDAC)
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Activity of histone acetyltransferase(HAT)
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Superoxide Dismutase
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • 8-Isoprostane
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Neutrophilic granulocytes in blood routine examination
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • White blood cells in blood routine examination
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Monocytes in blood routine examination
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Eosinophilic granulocytes in blood routine examination
    • Time Frame: Baseline and 24 weeks
      Safety Issue?: No
  • Number of participants with Adverse events as a measure of safety and tolerability
    • Time Frame: 24 weeks
      Safety Issue?: Yes
  • Plasma Concentration of Theophylline
    • Time Frame: 24 weeks
      Safety Issue?: Yes
[h=2]Criteria for Participation in this Clinical Trial[/h]
[h=3]Inclusion Criteria[/h]
  • Patients between 18-70 years old with non-cystic fibrosis(CF) bronchiectasis, free from acute exacerbations for at least 3 months.Stable phase of the disease.
[h=3]Exclusion Criteria[/h]
  • Patients with a cigarette smoking history of more than 10 packs-year. Patients with COPD. Patients with traction bronchiectasis due to advanced fibrosis. Patients with known intolerance for theophylline. Patients with asthma. Patients with other disease disturbing outcomes of the trials. Patients without consent.
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: 70 Years
Are Healthy Volunteers Accepted for this Clinical Trial: No
[h=2]Clinical Trial Investigator Information[/h]
  • Lead Sponsor
    • The First Affiliated Hospital of Guangzhou Medical University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Xugang, Medical Doctor – The First Affiliated Hospital of Guangzhou Medical University
  • Overall Official(s)
    • Chen Rongchang, Professor, Study Director, institute vice director
    • Zhong Nanshan, Professor, Study Director, institute director
[h=2]Additional Information on this Clinical Trial[/h]Information obtained from ClinicalTrials.gov on February 10, 2013
Link to the current ClinicalTrials.gov record. – http://clinicaltrials.gov/show/NCT01769898
Study ID Number: theophylline in bronchiectasis
ClinicalTrials.gov Identifier: NCT01769898
Health Authority: China: Ethics Committee

[h=2]Source[/h]Clinical Trials content is provided directly by the US National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of information about a specific clinical trial contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01769898
 
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JustaCFmom said:
If anyone likes reading this stuff....
http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70005-5/fulltext
Click to expand...


[h=1]Airway Clearance in Bronchiectasis: Breaking the Infection–Inflammation Cycle[/h]
+ Author Affiliations

  • The Alfred Hospital
    Melbourne, Victoria, Australia

To the Editor:
Therapies aimed at airway mucus clearance in bronchiectasis are broadly recommended (1–3) and may reduce airway microbial and inflammatory burden. In the short term, these therapies may have an impact on symptoms and exacerbation frequency, while long-term impacts may benefit neutrophilic airway inflammation and consequent airway wall damage and airflow obstruction. A variety of mucoactive agents have been trialled in bronchiectasis, although little is understood of the mechanisms of action.
Reeves and coworkers (4) describe a decrease in sputum IL-8 in patients with cystic fibrosis (CF) after inhaled hypertonic saline (HTS). This finding is compelling, potentially linking mucoactive therapy with HTS with antiinflammatory effect by reduced neutrophil chemotaxis, reduced neutrophil recruitment, and thereby reduced neutrophilic airway inflammation. Isotonic saline (0.9%), however, may also provide some airway clearance benefit in bronchiectasis (5), and so an effect specifically attributed to HTS and not IS needs rigorous confirmation.
In the current study, bronchoalveolar lavage fluid from individuals with CF, incubated with increasing concentrations of NaCl (thought to disaggregate IL-8–glycosaminoglycan [GAG] complexes) was associated with a fall in detectable GAG–IL-8 complexes. Unfortunately, the difference in generation of free IL-8 between HTS and IS was not reported.
The degradation of free IL-8 is reported to be inhibited by the use of protease inhibitors (PMSF and Pefabloc), yet when CF sputum samples were treated with protease inhibitors no difference in IL-8 was observed before or after HTS inhalation, and the effects of IS on sputum IL-8 levels were not reported. Encouragingly, neutrophilic chemotactic activity was diminished after treatment with HTS, although again the impact of IS on neutrophil chemotaxis was not reported and cannot be inferred. The design of the serine protease inhibitor experiments appears to show significant impact of intrinsic serine proteases (presumably including neutrophil-derived neutrophil elastase) on both IL-8 detection in airway and neutrophil chemotactic activity.
The vicious cycle of infection, inflammation, and tissue damage in bronchiectasis is yet to unravel. This study suggests that HTS may reduce airway inflammation in CF bronchiectasis, and this benefit may derive from the clearance of IL-8. However, this benefit may also be ascribed to the clearance of serine proteases and other mediators from the airway. Unfortunately, the current study design does not allow us to distinguish between a benefit derived from airway clearance, such as repeated expectoration (or repeated bronchoalveolar lavage), or the mucoactive agent HTS. Similarly, no conclusion can be drawn regarding a difference of effect between HTS and IS.

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[h=2]Footnotes[/h]


  • Copyright © 2012 by the American Thoracic Society
Previous Section

[h=2]References[/h]
  • 1.↵
    • Chang AB,
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    . British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010;65:577.
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  • 4.↵
    • Reeves EP,
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    . Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis. Am J Respir Crit Care Med 2011;183:1517–1523.
    Abstract/FREE Full Text

  • 5.↵
    • Nicolson CH,
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    . The long term effect of inhaled hypertonic saline (6%) in non cystic fibrosis bronchiectasis [abstract]. Am J Respir Crit Care Med 2010;181:A3183.
    FREE Full Text
 
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