The Effect of Theophylline in the Treatment of Bronchiectasis

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by The First Affiliated Hospital of Guangzhou Medical University
Sponsor:
Information provided by (Responsible Party):
Xugang, The First Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier:
NCT01684683
First received: September 11, 2012
Last updated: June 16, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Bronchiectasis
Drug: Theophylline
Drug: Placebo(for Theophylline)
Phase 4

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

Resource links provided by NLM:


Further study details as provided by The First Affiliated Hospital of Guangzhou Medical University:

Primary Outcome Measures:
  • Scores of the St.George's Respiratory Questionnaire [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Number of Exacerbations [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  • Scores of The Leicester Cough Questionnaire [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  • 24 Hour Sputum Volume [ Time Frame: Every day for 24 weeks ] [ Designated as safety issue: No ]
  • Activity of histone deacetylase(HDAC) [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    HDACs are extracted from cells in blood.

  • Activity of histone acetyltransferase(HAT) [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    HATs are extracted from cells in blood.

  • Lung function [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    Lung function as measured by FEV1, FVC, FEV1%, FEV1/FVC, FEF25-75 values following American Thoracic Society(ATS) guidelines

  • Induced sputum culture [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  • Induced Sputum Cytology Count [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  • Interleukin-6(IL-6) [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    Test IL-6 both in blood and sputum.

  • C-Reactive Protein [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  • To evaluate change in patients' Clinical Data [ Time Frame: Every day for 24 weeks ] [ Designated as safety issue: No ]
    Clinical Data contain dyspnea, cough, wheezes, hemoptysis, sputum characteristics, sputum volume.

  • Number of participants with adverse events [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    Test IL-8 both in blood and sputum.

  • IL-10 [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    Test IL-10 both in blood and sputum.

  • Human Tumor Necrosis Factor α(TNF-α) [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
    Test TNF-α both in blood and sputum.

  • 8-Isoprostane [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]
  • Blood routine examination [ Time Frame: At 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: November 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Theophylline
Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks
Drug: Theophylline
Theophylline 0.1 bid
Other Name: 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)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684683

Contacts
Contact: Xu Gang, PhD Can 008613580375817 158572962@qq.com
Contact: Gao Yonghua, PhD Can 008615920489217 375891371@qq.com

Locations
China, Guangdong
State Key Laboratory of Respiratory Research Institute. Recruiting
Guangzhou City, Guangdong, China, 510000
Contact: Chen Rongchang, Professor    008613902273260    chenrc@vip.163.com   
Contact: Xu Gang, Phd Can    008613580375817    158572962@qq.com   
Sponsors and Collaborators
The First Affiliated Hospital of Guangzhou Medical University
Investigators
Study Director: Chen Rongchang, Professor institute vice director
Study Director: Zhong Nanshan, Professor institute director
  More Information

No publications provided

Responsible Party: Xugang, Doctor of Medicine, The First Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT01684683     History of Changes
Other Study ID Numbers: Xugang
Study First Received: September 11, 2012
Last Updated: June 16, 2013
Health Authority: China: Ethics Committee

Keywords provided by The First Affiliated Hospital of Guangzhou Medical University:
Bronchiectasis
Theophylline
Therapeutic Uses
HDAC
HAT
Random placebo study

Additional relevant MeSH terms:
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases
Theophylline
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 22, 2014