Clinical trial NCT01769898: The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis
Official title: The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bronchiectasis
Keywords: Bronchiectasis
Theophylline
Therapeutic Uses
HDAC
HAT
Random placebo study
ICS(inhaled corticosteroid)
corticosteroid
Inhaled corticosteroid
Lead sponsor: The First Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2013-01-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Quality of Life Assessment with St George's Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ)
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Mean number of exacerbations per patient per 24 weeks
timeFrame: Baseline and 24 weeks
measure: Changes of sputum characteristics from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: Changes of 24 hour sputum volume from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: Changes of mean forced expiratory flow between 25% and 75% of the FVC(FEF25-75)from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: Changes of forced vital capacity(FVC) from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: Changes of peak expiratory flow(PEF) from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: Induced sputum cytology count
timeFrame: Baseline and 24 weeks
measure: Changes of sputum culture from baseline to 24 weeks
timeFrame: Baseline and 24 weeks
measure: IL-6
timeFrame: Baseline and 24 weeks
measure: IL-8
timeFrame: Baseline and 24 weeks
measure: IL-10
timeFrame: At 24 weeks
measure: Tumor necrosis factor(TNF)α
timeFrame: Baseline and 24 weeks
measure: Activity of histone deacetylase(HDAC)
timeFrame: Baseline and 24 weeks
measure: Activity of histone acetyltransferase(HAT)
timeFrame: Baseline and 24 weeks
measure: 8-Isoprostane
timeFrame: Baseline and 24 weeks
measure: Neutrophilic granulocytes in blood routine examination
timeFrame: Baseline and 24 weeks
measure: White blood cells in blood routine examination
timeFrame: Baseline and 24 weeks
measure: Monocytes in blood routine examination
timeFrame: Baseline and 24 weeks
measure: Eosinophilic granulocytes in blood routine examination
timeFrame: Baseline and 24 weeks
measure: Number of participants with Adverse events as a measure of safety and tolerability
timeFrame: 24 weeks
measure: Plasma Concentration of Theophylline
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Guangzhou City
country: China
facility: State Key Laboratory of Respiratory Research Institute.
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: institute vice director
name: Chen Rongchang, Professor
role: STUDY_DIRECTOR
affiliation: institute director
name: Zhong Nanshan, Professor
role: STUDY_DIRECTOR
References: