<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01684683</url>
  </required_header>
  <id_info>
    <org_study_id>theophylline in NCFB</org_study_id>
    <nct_id>NCT01684683</nct_id>
  </id_info>
  <brief_title>The Effect of Theophylline in the Treatment of Bronchiectasis</brief_title>
  <official_title>Clinical Efficacy and Safety of Theophylline in the Treatment of Non-Cystic Fibrosis(NCF) Bronchiectasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Guangzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Affiliated Hospital of Guangzhou Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Theophylline was well recommended in the treatment of chronic obstructive pulmonary disease&#xD;
      (COPD) and asthma. However, there is no supporting evidence for their efficacy in the&#xD;
      treatment of bronchiectasis. Our hypothesis is that theophylline will play a role in&#xD;
      bronchiectasis. Our purpose is to examine the efficacy and safety of 24 weeks treatment with&#xD;
      theophylline in subjects with non-cystic fibrosis bronchiectasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For the reasons of lack of sufficient clinical trial evidences, there are no standard therapy&#xD;
      recommendations for bronchiectasis. Currently the treatments for bronchiectasis are mostly&#xD;
      based on experience gained from the treatment of COPD and cystic fibrosis(CF). The aims of&#xD;
      treatment for bronchiectasis are to improve the health-related quality of life, to slow down&#xD;
      the decrease of lung function, to reduce the exacerbation frequence and the mortality. The&#xD;
      mechanism of treatment are including: treating the underlying disease; improving drainage of&#xD;
      sputum; anti-infection; anti-inflammation; treating airway obstruction. A review written by&#xD;
      Peter J. Barnes describes that as a bronchodilator in COPD, theophylline may relax human&#xD;
      airways smooth muscle, have an anti-inflammation rols, and have an additional effect on&#xD;
      mucociliary clearance. Besides, theophylline can improve the activity of histone deacetylase,&#xD;
      which will reverse the resistant of corticosteroids. We hypothesis that theophylline will&#xD;
      have the same effect in subjects with NCF-bronchiectasis as in subjects with COPD. Our trial&#xD;
      may give an evidence of using theophylline in treatment of bronchiectasis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Scores of the St.George's Respiratory Questionnaire</measure>
    <time_frame>At 24 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Number of Exacerbations</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Scores of The Leicester Cough Questionnaire</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24 Hour Sputum Volume</measure>
    <time_frame>Every day for 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activity of histone deacetylase(HDAC)</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>HDACs are extracted from cells in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activity of histone acetyltransferase(HAT)</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>HATs are extracted from cells in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>Lung function as measured by FEV1, FVC, FEV1%, FEV1/FVC, FEF25-75 values following American Thoracic Society(ATS) guidelines</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Induced sputum culture</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Induced Sputum Cytology Count</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-6(IL-6)</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>Test IL-6 both in blood and sputum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive Protein</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate change in patients' Clinical Data</measure>
    <time_frame>Every day for 24 weeks</time_frame>
    <description>Clinical Data contain dyspnea, cough, wheezes, hemoptysis, sputum characteristics, sputum volume.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Theophylline</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IL-8</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>Test IL-8 both in blood and sputum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IL-10</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>Test IL-10 both in blood and sputum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Human Tumor Necrosis Factor α（TNF-α)</measure>
    <time_frame>At 24 weeks</time_frame>
    <description>Test TNF-α both in blood and sputum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>8-Isoprostane</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood routine examination</measure>
    <time_frame>At 24 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Bronchiectasis</condition>
  <arm_group>
    <arm_group_label>Theophylline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo(for Theophylline sustained-release tablet) tablet by mouth 100mg every 12hours for 24weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Theophylline</intervention_name>
    <description>Theophylline 0.1 bid</description>
    <arm_group_label>Theophylline</arm_group_label>
    <other_name>Theophylline Sustained-Release Tablet.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo(for Theophylline)</intervention_name>
    <description>Starch tablet manufactured to Theophylline 100mg (Theophylline Stained-Release Tablet)</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients between 18-70 years old with non-CF bronchiectasis ,free from acute&#xD;
             exacerbations for at least 3 months.Stable phase of the disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a cigarette smoking history of more than 10 packs-year. Patients with&#xD;
             COPD. Patients with traction bronchiectasis due to advanced fibrosis. Patients with&#xD;
             known intolerance for theophylline. Patients with asthma. Patients with other disease&#xD;
             disturbing outcomes of the trials. Patients without consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chen Rongchang, Professor</last_name>
    <role>Study Director</role>
    <affiliation>institute vice director</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zhong Nanshan, Professor</last_name>
    <role>Study Director</role>
    <affiliation>institute director</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>State Key Laboratory of Respiratory Research Institute.</name>
      <address>
        <city>Guangzhou City</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <last_update_submitted>March 10, 2015</last_update_submitted>
  <last_update_submitted_qc>March 10, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 11, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The First Affiliated Hospital of Guangzhou Medical University</investigator_affiliation>
    <investigator_full_name>Xugang</investigator_full_name>
    <investigator_title>Doctor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Bronchiectasis</keyword>
  <keyword>Theophylline</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>HDAC</keyword>
  <keyword>HAT</keyword>
  <keyword>Random placebo study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchiectasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Theophylline</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01684683
org study id: theophylline in NCFB
nct id: NCT01684683
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Scores of the St.George's Respiratory Questionnaire
time frame: At 24 weeks
measure: The Number of Exacerbations
time frame: At 24 weeks
measure: Scores of The Leicester Cough Questionnaire
time frame: At 24 weeks
measure: 24 Hour Sputum Volume
time frame: Every day for 24 weeks
measure: Activity of histone deacetylase(HDAC)
time frame: At 24 weeks
description: HDACs are extracted from cells in blood.
measure: Activity of histone acetyltransferase(HAT)
time frame: At 24 weeks
description: HATs are extracted from cells in blood.
measure: Lung function
time frame: At 24 weeks
description: Lung function as measured by FEV1, FVC, FEV1%, FEV1/FVC, FEF25-75 values following American Thoracic Society(ATS) guidelines
measure: Induced sputum culture
time frame: At 24 weeks
measure: Induced Sputum Cytology Count
time frame: At 24 weeks
measure: Interleukin-6(IL-6)
time frame: At 24 weeks
description: Test IL-6 both in blood and sputum.
measure: C-Reactive Protein
time frame: At 24 weeks
measure: To evaluate change in patients' Clinical Data
time frame: Every day for 24 weeks
description: Clinical Data contain dyspnea, cough, wheezes, hemoptysis, sputum characteristics, sputum volume.
measure: Number of participants with adverse events
time frame: Up to 24 weeks
description: Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.
measure: Plasma Concentration of Theophylline
time frame: At 24 weeks
description: 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)
measure: IL-8
time frame: At 24 weeks
description: Test IL-8 both in blood and sputum.
measure: IL-10
time frame: At 24 weeks
description: Test IL-10 both in blood and sputum.
measure: Human Tumor Necrosis Factor α（TNF-α)
time frame: At 24 weeks
description: Test TNF-α both in blood and sputum.
measure: 8-Isoprostane
time frame: At 24 weeks
measure: Blood routine examination
time frame: At 24 weeks
arm group label: Theophylline
arm group type: Experimental
description: Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo(for Theophylline sustained-release tablet) tablet by mouth 100mg every 12hours for 24weeks
intervention type: Drug
intervention name: Theophylline
description: Theophylline 0.1 bid
arm group label: Theophylline
other name: Theophylline Sustained-Release Tablet.
intervention type: Drug
intervention name: Placebo(for Theophylline)
description: Starch tablet manufactured to Theophylline 100mg (Theophylline Stained-Release Tablet)
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Chen Rongchang, Professor
role: Study Director
affiliation: institute vice director
last name: Zhong Nanshan, Professor
role: Study Director
affiliation: institute director
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: The First Affiliated Hospital of Guangzhou Medical University
investigator full name: Xugang
investigator title: Doctor of Medicine
mesh term: Bronchiectasis
mesh term: Theophylline