The Effect of Theophylline in the Treatment of Bronchiectasis

Sponsor

The First Affiliated Hospital of Guangzhou Medical University (Other)

Overall Status

Completed

CT.gov ID

NCT01684683

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Theophylline was well recommended in the treatment of chronic obstructive pulmonary disease (COPD) and asthma. However, there is no supporting evidence for their efficacy in the treatment of bronchiectasis. Our hypothesis is that theophylline will play a role in bronchiectasis. Our purpose is to examine the efficacy and safety of 24 weeks treatment with theophylline in subjects with non-cystic fibrosis bronchiectasis.

Condition or Disease	Intervention/Treatment	Phase
Bronchiectasis	Drug: Theophylline Drug: Placebo(for Theophylline)	Phase 4

Detailed Description

For the reasons of lack of sufficient clinical trial evidences, there are no standard therapy recommendations for bronchiectasis. Currently the treatments for bronchiectasis are mostly based on experience gained from the treatment of COPD and cystic fibrosis(CF). The aims of treatment for bronchiectasis are to improve the health-related quality of life, to slow down the decrease of lung function, to reduce the exacerbation frequence and the mortality. The mechanism of treatment are including: treating the underlying disease; improving drainage of sputum; anti-infection; anti-inflammation; treating airway obstruction. A review written by Peter J. Barnes describes that as a bronchodilator in COPD, theophylline may relax human airways smooth muscle, have an anti-inflammation rols, and have an additional effect on mucociliary clearance. Besides, theophylline can improve the activity of histone deacetylase, which will reverse the resistant of corticosteroids. We hypothesis that theophylline will have the same effect in subjects with NCF-bronchiectasis as in subjects with COPD. Our trial may give an evidence of using theophylline in treatment of bronchiectasis.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Clinical Efficacy and Safety of Theophylline in the Treatment of Non-Cystic Fibrosis(NCF) Bronchiectasis

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Theophylline Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks	Drug: Theophylline Theophylline 0.1 bid Other Names: Theophylline Sustained-Release Tablet.
Placebo Comparator: placebo Placebo(for Theophylline sustained-release tablet) tablet by mouth 100mg every 12hours for 24weeks	Drug: Placebo(for Theophylline) Starch tablet manufactured to Theophylline 100mg (Theophylline Stained-Release Tablet)

Arm

Intervention/Treatment

Experimental: Theophylline

Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks

Drug: Theophylline

Theophylline 0.1 bid

Other Names:

Theophylline Sustained-Release Tablet.

Placebo Comparator: placebo

Placebo(for Theophylline sustained-release tablet) tablet by mouth 100mg every 12hours for 24weeks

Drug: Placebo(for Theophylline)

Starch tablet manufactured to Theophylline 100mg (Theophylline Stained-Release Tablet)

Outcome Measures

Primary Outcome Measures

Scores of the St.George's Respiratory Questionnaire [At 24 weeks]

Secondary Outcome Measures

The Number of Exacerbations [At 24 weeks]
Scores of The Leicester Cough Questionnaire [At 24 weeks]
24 Hour Sputum Volume [Every day for 24 weeks]
Activity of histone deacetylase(HDAC) [At 24 weeks]
HDACs are extracted from cells in blood.
Activity of histone acetyltransferase(HAT) [At 24 weeks]
HATs are extracted from cells in blood.
Lung function [At 24 weeks]
Lung function as measured by FEV1, FVC, FEV1%, FEV1/FVC, FEF25-75 values following American Thoracic Society(ATS) guidelines
Induced sputum culture [At 24 weeks]
Induced Sputum Cytology Count [At 24 weeks]
Interleukin-6(IL-6) [At 24 weeks]
Test IL-6 both in blood and sputum.
C-Reactive Protein [At 24 weeks]
To evaluate change in patients' Clinical Data [Every day for 24 weeks]
Clinical Data contain dyspnea, cough, wheezes, hemoptysis, sputum characteristics, sputum volume.
Number of participants with adverse events [Up to 24 weeks]
Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.
Plasma Concentration of Theophylline [At 24 weeks]
Venous blood was taken for plasma theophylline at the end of the treatment period. (At the very time of 2 hours after patients taken the pills)
IL-8 [At 24 weeks]
Test IL-8 both in blood and sputum.
IL-10 [At 24 weeks]
Test IL-10 both in blood and sputum.
Human Tumor Necrosis Factor α（TNF-α) [At 24 weeks]
Test TNF-α both in blood and sputum.
8-Isoprostane [At 24 weeks]
Blood routine examination [At 24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients between 18-70 years old with non-CF bronchiectasis ,free from acute exacerbations for at least 3 months.Stable phase of the disease.

Exclusion Criteria:

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.