Pulmonary Disease, Chronic Obstructive
Conditions
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.
Interventions
DRUGN-acetylcysteine
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.
DRUGPlacebo
Placebo: 3 placebo pills/day orally for 4 days prior to experimental procedures and 1 placebo pill orally on the day of the experiment.
Sponsors
Queen's University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Redox Status - Circulating Glutathione | pre-exercise value (day 4) | Fluorescent detection of plasma glutathione from samples collected during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
| Exercise Capacity - Time to Exhaustion | end-exercise value (Day 4) | Cycling time to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Skeletal Muscle Vascular Function - Capillary Blood Flow Dynamics (Mean Response Time) | Day 4 | Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
| Change in Central Cardiovascular Function - Cardiac Output | end-exercise value (Day 4) | During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
| Change in Pulmonary Ventilation - Minute Ventilation (VE) | end-exercise value (Day 4) | During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
| Change in Pulmonary Oxygen Uptake - Dynamics (Mean Response Time) | Day 4 | Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
| Change in Skeletal Muscle Deoxygenation - Dynamics (Mean Response Time) | Day 4 | Mean response time (MRT) evaluated during cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either N-acetylcysteine (NAC) or placebo pills | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | flu-like illness, orthopedic trauma | 1 | 1 |
| Overall Study | Usage of additional antioxidants | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
Exercise Capacity - Time to Exhaustion
Cycling time to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Time frame: end-exercise value (Day 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Exercise Capacity - Time to Exhaustion | 336 seconds | Standard Error 51 |
| Placebo | Exercise Capacity - Time to Exhaustion | 325 seconds | Standard Error 47 |
Primary
Plasma Redox Status - Circulating Glutathione
Fluorescent detection of plasma glutathione from samples collected during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Time frame: pre-exercise value (day 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Plasma Redox Status - Circulating Glutathione | 8.97 micromolar | Standard Error 0.61 |
| Placebo | Plasma Redox Status - Circulating Glutathione | 7.05 micromolar | Standard Error 0.49 |
Secondary
Change in Central Cardiovascular Function - Cardiac Output
During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Time frame: end-exercise value (Day 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Central Cardiovascular Function - Cardiac Output | 12.5 liters/min | Standard Error 1 |
| Placebo | Change in Central Cardiovascular Function - Cardiac Output | 12.1 liters/min | Standard Error 0.9 |
Secondary
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)
Time frame: Day 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Pulmonary Oxygen Uptake - Dynamics (Mean Response Time) | 63.0 seconds | Standard Error 5.2 |
| Placebo | Change in Pulmonary Oxygen Uptake - Dynamics (Mean Response Time) | 62.2 seconds | Standard Error 4.4 |
Secondary
Change in Pulmonary Ventilation - Minute Ventilation (VE)
During cycling to exhaustion during day 4 of each experimental arm (placebo vs. N-acetylcysteine)
Time frame: end-exercise value (Day 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Pulmonary Ventilation - Minute Ventilation (VE) | 78.7 liters/min | Standard Error 7.6 |
| Placebo | Change in Pulmonary Ventilation - Minute Ventilation (VE) | 75.8 liters/min | Standard Error 6.6 |
Secondary
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)
Time frame: Day 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Skeletal Muscle Deoxygenation - Dynamics (Mean Response Time) | 19.0 seconds | Standard Error 1.3 |
| Placebo | Change in Skeletal Muscle Deoxygenation - Dynamics (Mean Response Time) | 19.0 seconds | Standard Error 2.5 |
Secondary
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)
Time frame: Day 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Skeletal Muscle Vascular Function - Capillary Blood Flow Dynamics (Mean Response Time) | 65.4 seconds | Standard Error 4.6 |
| Placebo | Change in Skeletal Muscle Vascular Function - Capillary Blood Flow Dynamics (Mean Response Time) | 66.5 seconds | Standard Error 7.6 |