The Role of Theophylline Plus Low-dose Formoterol-budesonide in 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:
NCT01769898
First received: January 15, 2013
Last updated: October 30, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Bronchiectasis
Drug: Formoterol-budesonide
Drug: Theophylline
Drug: Placebo
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: The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Quality of Life Assessment with St George's Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean number of exacerbations per patient per 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Exacerbations defined by persistent (≥ 24 h) deterioration in at least three respiratory symptoms, including cough, dyspnea, hemoptysis, increased sputum purulence or volume, chest pain (with or without fever).

  • Changes of sputum characteristics from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Changes of 24 hour sputum volume from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as 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 ] [ Designated as safety issue: No ]
  • Changes of forced vital capacity(FVC) from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Changes of peak expiratory flow(PEF) from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Induced sputum cytology count [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Changes of sputum culture from baseline to 24 weeks [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • IL-6 [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Test IL-6 both in blood and sputum.

  • IL-8 [ Time Frame: Baseline and 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.

  • Tumor necrosis factor(TNF)α [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Test TNF-α both in blood and sputum.

  • Activity of histone deacetylase(HDAC) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    HDACs are extracted from cells in blood.

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

  • 8-Isoprostane [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Neutrophilic granulocytes in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • White blood cells in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Monocytes in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Eosinophilic granulocytes in blood routine examination [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
  • Number of participants with Adverse events as a measure of safety and tolerability [ Time Frame: 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: 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)


Estimated Enrollment: 60
Study Start Date: July 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Formoterol-budesonide
Formoterol-budesonide combined treatment (4.5µg/160µg Q12H)
Other Name: Symbicort tu rbuhaler
Drug: Placebo
Placebo for theophylline 0.1 Q12H
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.

Drug: Formoterol-budesonide
Formoterol-budesonide combined treatment (4.5µg/160µg Q12H)
Other Name: Symbicort tu rbuhaler
Drug: Theophylline
Theophylline 0.1 Q12H
Other Name: Theophylline Sustained-Release Tablet

Detailed Description:

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.

  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-cystic fibrosis(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: NCT01769898

Locations
China, Guangdong
The First Affiliated Hospital of Guangzhou Medical University Recruiting
Guangzhou, Guangdong, China, 510000
Contact: Gang Xu       158572952@qq.com   
Sub-Investigator: Yonghua Gao         
State Key Laboratory of Respiratory Research Institute. Not yet recruiting
Guangzhou City, Guangdong, China, 510000
Contact: Chen Rongchang, Professor    008613902273260    chenrc@vip.163.com   
Contact: Xu Gang, PHD    008613580375817    158572962@qq.com   
Principal Investigator: Gang Xu, ph.D.         
Sub-Investigator: Weijie Guan, ph.D.         
Sub-Investigator: Yonghua Gao, ph.D.         
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, Medical Doctor, The First Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT01769898     History of Changes
Other Study ID Numbers: theophylline in bronchiectasis
Study First Received: January 15, 2013
Last Updated: October 30, 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
ICS(inhaled corticosteroid)
corticosteroid
Inhaled corticosteroid

Additional relevant MeSH terms:
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases
Budesonide
Formoterol
Theophylline
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014