Effect of Tiotropium on Airway Remodeling in Patients With Early Stage COPD Accessed by Optical Coherence Tomography

Study Overview
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Brief Summary
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The study aims to explore the effect of tiotropium on airway remodeling by using Endobronchial Optical Coherence Tomography (EB-OCT). We enrolled patients with GOLD I stage COPD. All the patients will be divided into four groups randomly to receive SABA as needed with or without regular use of tiotropium. Changes of airway morphology (accessed by EB-OCT), pulmonary function, QOL, and SABA usage will be obtained.

Official Title
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Effect of Tiotropium on Airway Remodeling in Patients With Early Stage COPD Accessed by Optical Coherence Tomography

Conditions
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Airway Remodeling

Intervention / Treatment
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* Drug: Tiotropium Inhalation Powder [Spiriva] 0.018mg
* Drug: Salbutamol sulphate aerosol (Ventolin) 0.01mg


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria Over 40 yrs; Male or female Diagnosed with COPD Pre-bronchodilator FEV1 ≥80% pred ; Patients must be able to perform all study related procedures Exclusion Criteria: Patients with other lung diseases (such as bronchiectasis, pneumothorax, pleural effusion, airway deformation, lung surgery, etc.). Patients have poor compliance and are unwilling to receive medication regularly. Other complications of bronchoscopy or intolerance of bronchoscopy procedure.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium (0-12 month) + SABA as needed<br>During the 2 years treatment phase patients will be administered with tiotropium bromide (Spiriva) capsule 18μg once daily from baseline to the 12th months. Any long acting bronchodilator will not be used from the 12 to 24 months. Salbutamol sulphate aerosol (Ventolin) will be administered as concomitant medication treatment when exacerbation occurs. | Drug: Tiotropium Inhalation Powder [Spiriva] 0.018mg<br>* Tiotropium bromide (Spiriva) capsule 18μg once daily inhaled.<br>* Other names: Spiriva;Drug: Salbutamol sulphate aerosol (Ventolin) 0.01mg<br>* As needed use of salbutamol sulphate aerosol (Ventolin) when exacerbation happens<br>* Other names: Ventolin;|
| Experimental: Tiotropium (0-24 month) + SABA as needed<br>During the 2 years treatment phase patients will be administered with tiotropium bromide (Spiriva) capsule 18μg once daily from baseline to the 24th months. Salbutamol sulphate aerosol (Ventolin) will be administered as concomitant medication treatment when exacerbation occurs. | Drug: Tiotropium Inhalation Powder [Spiriva] 0.018mg<br>* Tiotropium bromide (Spiriva) capsule 18μg once daily inhaled.<br>* Other names: Spiriva;Drug: Salbutamol sulphate aerosol (Ventolin) 0.01mg<br>* As needed use of salbutamol sulphate aerosol (Ventolin) when exacerbation happens<br>* Other names: Ventolin;|
| Other: SABA as needed only<br>During the 2 years treatment phase patients will be administered with salbutamol sulphate aerosol (Ventolin) when exacerbation occurs. Any long acting bronchodilator will not be used during the 2 years treatment phase. | Drug: Salbutamol sulphate aerosol (Ventolin) 0.01mg<br>* As needed use of salbutamol sulphate aerosol (Ventolin) when exacerbation happens<br>* Other names: Ventolin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the inner luminal area (Ai) of the 3th to 9th generation bronchi at month 24 | To evaluate the effects of Tiotropium in ameliorating airway remodeling in early stage COPD | Ai accessed by endobronchial optical coherence tomography will be obtained at baseline, month 24. | 
| Change from baseline in the inner luminal area (Ai) of the 3th to 9th generation bronchi at month 12 | To evaluate the effects of Tiotropium in ameliorating airway remodeling in early stage COPD | Ai accessed by endobronchial optical coherence tomography will be obtained at month 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the airway wall area percentage (Aw%) of the 3th to 9th generation bronchi at month 12 | To evaluate the effects of Tiotropium in ameliorating airway remodeling in early stage COPD | Aw% accessed by endobronchial optical coherence tomography will be obtained at baseline, month 12. | 
| Change from baseline in the airway wall area percentage (Aw%) of the 3th to 9th generation bronchi at month 24 | To evaluate the effects of Tiotropium in ameliorating airway remodeling in early stage COPD | Aw% accessed by endobronchial optical coherence tomography will be obtained at month24. | 
| Change from baseline in trough FEV1 | To evaluate the effects of Tiotropium in improving lung function | Pulmonary function test will be performed at baseline, month 6, 12, 18 and 24. | 
| Change from baseline in resonant frequency (Fres) at month 6, 12, 18 and 24. | To evaluate the effects of Tiotropium in improving lung function | IOS will be performed at baseline, month 6, 12, 18 and 24. | 
| Change from baseline in peripheral airway resistance (R5-R20) | To evaluate the effects of Tiotropium in improving lung function | IOS will be performed at baseline, month 6, 12, 18 and 24. | 
| Total times of SABA usage | To evaluate the times of SABA administration | During the two years treatment period, times of SABA administration will be recored. | 
| Total dosage of SABA usage | To evaluate the dosage of SABA administration | During the two years treatment period, the dosage of SABA administration will be recored. |