The Effect of High Dose N-acetylcysteine on Airtrapping and Airway Resistance in Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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This study is to investigate the add-on effect of high dose NAC (600mg tablet twice daily) on reduction of airtrapping and airway resistance in stable COPD patients as well as to study it's effect in reducing exacerbation, improving exercise capacity and quality of life in stable COPD patients.

Detailed Description
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Background: The mucolytic and antioxidant effects of N-acetylcysteine (NAC) may be of great value in treatment of COPD patients. However, previous studies fail to demonstrate the beneficial effect of NAC. This may be due to insufficient dose of NAC used as well as inadequate outcome parameters measured in the past studies. Objective of study: This study is to investigate the add-on effect of high dose NAC (600mg tablet twice daily) on reduction of airtrapping and airway resistance in stable COPD patients as well as to study it's effect in reducing exacerbation, improving exercise capacity and quality of life in stable COPD patients. Study design: Randomized double blinded placebo controlled trial in Kwong Wah Hospital Methodology: Patients are recruited in Kwong Wah Hospital if they fulfill the spirometric criteria of COPD. Eligible subjects will be randomized into the treatment (NAC 600mg tablet twice daily) and placebo group after completion of run in period. NAC and placebo will be prescribed accordingly in addition to their usual therapy. Both patients and investigators are blinded about the group allocation. Baseline assessment will be done and patients will be followed up at 16th weeks and 52th week of the study. During each follow-up visit, hyperinflation parameters like inspiratory capacity (IC) will be measured by plethysmography. Airway resistance will be measured by both plethysmography and impulse oscillometry machine. Exercise capacity (6 min walking distance) and quality of life are also recorded during each follow up. The difference of the above parameters between the 2 groups (drug and placebo group) will be analyszed by the Repeated measures ANOVA test

Official Title
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The Effect of High Dose N-acetylcysteine on Airtrapping and Airway Resistance of Chronic Obstructive Pulmonary disease-a Double Blinded Randomized Placebo Controlled Trial

Conditions
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COPD

Intervention / Treatment
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* Drug: N-acetycysteine (600mg twice daily)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spirometry diagnosed COPD with FEV1/FVC ratio less than 70% and FEV1 less than 80% predicted clinically stable and exacerbation free in the past 4 weeks history of at least one COPD exacerbation in the past one year Exclusion Criteria: patients allergic or intolerant to NAC Recent use of NAC in the past one month history of asthma, non COPD respiratory disorders like bronchiectasis, pneumoconiosis or any active pulmonary infection patients on long term steroid patients on long term oxygen therapy or non invasive ventilation

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (600mg twice daily) | Drug: Placebo<br>* Placebo (600mg twice daily)<br>|
| Active Comparator: N-acetylcysteine<br>N-acetylcysteine (600mg twice daily) | Drug: N-acetycysteine (600mg twice daily)<br>* N-acetycysteine (600mg twice daily) for one year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airtrapping in COPD patients | The airtrapping of COPD patients is measured by inspiratory capacity (IC), using plethsmography (MedGraphics Elite series) | At baseline (time 0 week) | 
| Airtrapping in COPD patients | The airtrapping of COPD patients is measured by inspiratory capacity (IC), using plethsmography (MedGraphics Elite series) | At 16th week | 
| Airtrapping in COPD patients | The airtrapping of COPD patients is measured by inspiratory capacity (IC), using plethsmography (MedGraphics Elite series) | At 52th Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway resistance in COPD patients | Airway resistance is measured by plethsmography (Medgraphics Elite series) and impulse oscillometry. | At baseline ( time 0) | 
| Airway resistance in COPD patients | Airway resistance is measured by plethsmography (Medgraphics Elite series) and impulse oscillometry. | At 16th week | 
| Airway resistance in COPD patients | Airway resistance is measured by plethsmography (Medgraphics Elite series) and impulse oscillometry. | At 52th week | 
| Exercise capacity | Exercise capacity is measured by 6-min-walking distance (6MWD)and it is performed by a trained physiotherapist | At baseline ( time 0) | 
| Exercise capacity | Exercise capacity is measured by 6-min-walking distance (6MWD)and it is performed by a trained physiotherapist | At 16th week | 
| Exercise capacity | Exercise capacity is measured by 6-min-walking distance (6MWD)and it is performed by a trained physiotherapist | At 52th week | 
| Quality of life | Quality of life is assessed by using the St Qeorge Respiratory Questionnaire (SQRQ)and it will be performed by a trained physiotherapist | At baseline (time 0) | 
| Quality of life | Quality of life is assessed by using the St Qeorge Respiratory Questionnaire (SQRQ)and it will be performed by a trained physiotherapist | At 16th week | 
| Quality of life | Quality of life is assessed by using the St Qeorge Respiratory Questionnaire (SQRQ)and it will be performed by a trained physiotherapist | At 52th week | 
| COPD exacerbation rate | The number of COPD exacerbation (exacerbation was defined as 2 out of 3 of the following criteria; 1.increase in shortness of breath, 2. increase in sputum purulence or 3. increase in sputum volume) will be assessed and documented | At 52th week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, N-acetylcysteine, airtrapping, airway resistance, antioxidant