The Effect of Theophylline in the Treatment of Bronchiectasis

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

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.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Drug: Theophylline; Drug: Placebo(for Theophylline)

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 Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou City, Guangdong, China, 510000
      • State Key Laboratory of Respiratory Research Institute.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Scores of the St.George's Respiratory Questionnaire	At 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	HDACs are extracted from cells in blood.	At 24 weeks
Activity of histone acetyltransferase(HAT)	HATs are extracted from cells in blood.	At 24 weeks
Lung function	Lung function as measured by FEV1, FVC, FEV1%, FEV1/FVC, FEF25-75 values following American Thoracic Society(ATS) guidelines	At 24 weeks
Induced sputum culture		At 24 weeks
Induced Sputum Cytology Count		At 24 weeks
Interleukin-6(IL-6)	Test IL-6 both in blood and sputum.	At 24 weeks
C-Reactive Protein		At 24 weeks
To evaluate change in patients' Clinical Data	Clinical Data contain dyspnea, cough, wheezes, hemoptysis, sputum characteristics, sputum volume.	Every day for 24 weeks
Number of participants with adverse events	Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.	Up to 24 weeks
Plasma Concentration of Theophylline	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)	At 24 weeks
IL-8	Test IL-8 both in blood and sputum.	At 24 weeks
IL-10	Test IL-10 both in blood and sputum.	At 24 weeks
Human Tumor Necrosis Factor α（TNF-α)	Test TNF-α both in blood and sputum.	At 24 weeks
8-Isoprostane		At 24 weeks
Blood routine examination		At 24 weeks

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: September 11, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimate): September 13, 2012

Study Record Updates

• Last Update Posted (Estimate): March 11, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Bronchiectasis; Therapeutic Uses; HDAC; Theophylline; HAT; Random placebo study
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Theophylline
• Other Study ID Numbers: theophylline in NCFB