Effects of N-acetylcysteine on Cardiorespiratory Control in COPD Patients With Mild-to-moderate Airflow Obstruction

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to determine whether pharmacological treatment with N-acetylcysteine improves central and peripheral cardiorespiratory control and physical capacity in COPD patients with mild-to-moderate airflow obstruction.

Detailed Description
-----------------
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Cardiovascular complications constitute the main causes of poor physical capacity and healthcare resources utilization in COPD. There is emerging evidence that these impairments have a major impact on the health of patients with mild-to-moderate disease, the largest sub-population of COPD. This important problem, however, is currently neglected as no specific pharmacological treatment is offered to these patients. Recent studies indicate that vascular abnormalities are mediated, at least in part, by circulating inflammatory substances and direct damage of the arteries by oxygen radicals (oxidative stress). The current investigation will test the hypothesis that N-acetylcysteine (NAC), via its anti-inflammatory and antioxidant properties, improves systemic vascular function and physical capacity in COPD patients with mild-to-moderate airflow obstruction.

Official Title
-----------------
Systemic Vascular Dysfunction in COPD Patients With Mild-to-moderate Airflow Obstruction: Pharmacological Treatment With N-acetylcysteine

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: stable COPD with mild-to-moderate airflow obstruction as indicated by the low ratio between forced expiratory volume in one second and forced vital capacity (FEV1/FVC<0.7) together with post-bronchodilator FEV1≥60% predicted under optimized clinical treatment as judged by the accompanying physician Exclusion Criteria: unable to perform all experimental procedures and/or provide informed consent; hospital admission in the previous 6 weeks; exercise training program in the previous 6 months; any condition that could interfere with the ability to exercise; diagnosed psychiatric or cognitive disorders; type I insulin-dependent diabetes mellitus; excessively over-weight (BMI>35kg/m²); other diagnosed cardiorespiratory disorders (e.g., chronic heart failure, peripheral artery disease).

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: N-acetylcysteine<br>Pharmacological treatment with N-acetylcysteine (NAC) pills | Drug: N-acetylcysteine<br>* Pharmacological treatment with N-acetylcysteine (NAC): 3 pills of 600 mg of NAC/day orally for 4 days prior to experimental procedures and 1 pill of 600 mg of NAC orally on the day of the experiment.<br>* Other names: NAC pills;|
| Placebo Comparator: Placebo<br>Treatment with placebo pills | Drug: Placebo<br>* Placebo: 3 placebo pills/day orally for 4 days prior to experimental procedures and 1 placebo pill orally on the day of the experiment.<br>* Other names: Placebo pills;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Redox Status - Circulating Glutathione | Fluorescent detection of plasma glutathione from samples collected during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | pre-exercise value (day 4) | 
| Exercise Capacity - Time to Exhaustion | Cycling time to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | end-exercise value (Day 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Central Cardiovascular Function - Cardiac Output | During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | end-exercise value (Day 4) | 
| Change in Skeletal Muscle Deoxygenation - Dynamics (Mean Response Time) | Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | Day 4 | 
| Change in Skeletal Muscle Vascular Function - Capillary Blood Flow Dynamics (Mean Response Time) | Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | Day 4 | 
| Change in Pulmonary Oxygen Uptake - Dynamics (Mean Response Time) | Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | Day 4 | 
| Change in Pulmonary Ventilation - Minute Ventilation (VE) | During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) | end-exercise value (Day 4) |