The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis

Bronchiectasis Clinical Trial

Official title:

The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01769898
• Other study ID #: theophylline in bronchiectasis
• Status: Completed
• Phase: Phase 4
• First received: January 15, 2013
• Last updated: March 10, 2015
• Start date: July 2013
• Est. completion date: November 2014

Study information

• Verified date: March 2015
• Source: The First Affiliated Hospital of Guangzhou Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• Formoterol-budesonide
Formoterol-budesonide combined treatment (4.5µg/160µg Q12H)
• Theophylline
Theophylline 0.1 Q12H
• Placebo
Placebo for theophylline 0.1 Q12H

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	State Key Laboratory of Respiratory Research Institute.	Guangzhou City	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of Life Assessment with St George's Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ)		Baseline and 24 weeks	No
Secondary	Mean number of exacerbations per patient per 24 weeks	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).	Baseline and 24 weeks	No
Secondary	Changes of sputum characteristics from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	Changes of 24 hour sputum volume from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	Changes of mean forced expiratory flow between 25% and 75% of the FVC(FEF25-75)from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	Changes of forced vital capacity(FVC) from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	Changes of peak expiratory flow(PEF) from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	Induced sputum cytology count		Baseline and 24 weeks	No
Secondary	Changes of sputum culture from baseline to 24 weeks		Baseline and 24 weeks	No
Secondary	IL-6	Test IL-6 both in blood and sputum.	Baseline and 24 weeks	No
Secondary	IL-8	Test IL-8 both in blood and sputum.	Baseline and 24 weeks	No
Secondary	IL-10	Test IL-10 both in blood and sputum.	At 24 weeks	No
Secondary	Tumor necrosis factor(TNF)a	Test TNF-a both in blood and sputum.	Baseline and 24 weeks	No
Secondary	Activity of histone deacetylase(HDAC)	HDACs are extracted from cells in blood.	Baseline and 24 weeks	No
Secondary	Activity of histone acetyltransferase(HAT)	HATs are extracted from cells in blood.	Baseline and 24 weeks	No
Secondary	8-Isoprostane		Baseline and 24 weeks	No
Secondary	Neutrophilic granulocytes in blood routine examination		Baseline and 24 weeks	No
Secondary	White blood cells in blood routine examination		Baseline and 24 weeks	No
Secondary	Monocytes in blood routine examination		Baseline and 24 weeks	No
Secondary	Eosinophilic granulocytes in blood routine examination		Baseline and 24 weeks	No
Secondary	Number of participants with Adverse events as a measure of safety and tolerability	Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.	24 weeks	Yes
Secondary	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)	24 weeks	Yes