Pilot Study to Assess the Effect of High Dose N-acetylcysteine (NAC) in Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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Studies suggest that N-acetylcysteine (NAC) potentially reduces inflammation and hyperinflation in patients with COPD. In this pilot study the efficacy, safety and tolerability of high dose NAC in 12 patients with moderate COPD will be examined. These patients will receive a placebo for 12 weeks and NAC for 12 weeks in a dosage of 3 times 600 mg a day on top of their usual medication in a randomized crossover design. All subjects will be followed for 28 weeks. The effect of high dose NAC on small airways will be assessed by measuring the total and peripheral airway resistance calculated with Computational Fluid Dynamics (CFD). The effect on oxidative stress will be assessed by measuring exhaled NO and specific markers (CRP, erythrocyte sedimentation rate, IL-6, 8-isoprostane, H2O2, TNF-alfa, glutathione, GPX, SOD and IL-8) in blood and Exhaled Breath Condensate (EBC). Dynamic and static lung volumes will be assessed by spirometry, body plethysmography and diffusion. Quality of life and symptoms will be assessed by the St George Respiratory Questionnaire.

Official Title
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Double Blind, Randomized, Placebo-controlled, Two-way Crossover, Pilot Study to Assess the Effect of High Dose N-acetylcysteine on Small Airways and on Inflammation and Oxidative Stress in COPD Patients.

Conditions
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COPD

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with documented COPD based on the following criteria: Smoking history of at least 10 pack-years Decreased Tiffeneau index (FEV1/(FVC < 0.70) Patients aged ≥ 40 years Patients who stopped smoking since more than 1 month Patients who present moderate COPD with an FEV1 between 50 and 80% of predicted (GOLD 2) Patients should be treated according to GOLD guidelines Exclusion Criteria: Unstable patients who developed an exacerbation during the last 8 weeks Patients who are current smokers or stopped less than 1 month Patients who are allergic to acetylcysteine or to another element of the product Patients with phenylketonuria or an untreated active peptic ulcer Patients with any stage kidney and/or heart insufficiency or hypertension Patients already treated with NAC for more than 6 months or during the last 3 months Patients on continuous treatment with oral, inhalation, intravenous or intramuscular corticosteroids Patients who are pregnant or are breast-feeding Patients who are treated with orally administered cephalosporins Patients using supplements containing antioxidants as vitamins C or E

Ages Eligible for Study
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Minimum Age: 40 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: N-acetylcysteine<br>* 600 mg TID for 12 weeks<br>|
| Placebo Comparator: 2<br> | Drug: placebo<br>* placebo tablet TID for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of high dose NAC (1800 mg)on small airways by measuring the total and peripheral airway resistance calculated with CFD |  | at baseline, after 12 weeks of placebo and after 12 weeks of NAC | 
| To assess the effect of high dose NAC (1800 mg)on oxidative stress by measuring exhaled NO and oxidative stress markers in blood and EBC |  | at baseline, after 12 weeks of placebo and after 12 weeks of NAC. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess dynamic and static lung volumes by spirometry, body plethysmography and diffusion |  | will be assessed at all visits | 
| To assess quality of life by the SGRQ |  | will be assessed at all visits | 
| To assess the tolerability and safety of high dose NAC |  | all visits |