Clinical trial NCT00969904: Pilot Study to Assess the Effect of High Dose N-acetylcysteine (NAC) in Chronic Obstructive Pulmonary Disease (COPD) Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COPD
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2009-09-01
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Patients with documented COPD based on the following criteria:

   * Smoking history of at least 10 pack-years
   * Decreased Tiffeneau index (FEV1/(FVC \< 0.70)
2. Patients aged ≥ 40 years
3. Patients who stopped smoking since more than 1 month
4. Patients who present moderate COPD with an FEV1 between 50 and 80% of predicted (GOLD 2)
5. Patients should be treated according to GOLD guidelines

Exclusion Criteria:

1. Unstable patients who developed an exacerbation during the last 8 weeks
2. Patients who are current smokers or stopped less than 1 month
3. Patients who are allergic to acetylcysteine or to another element of the product
4. Patients with phenylketonuria or an untreated active peptic ulcer
5. Patients with any stage kidney and/or heart insufficiency or hypertension
6. Patients already treated with NAC for more than 6 months or during the last 3 months
7. Patients on continuous treatment with oral, inhalation, intravenous or intramuscular corticosteroids
8. Patients who are pregnant or are breast-feeding
9. Patients who are treated with orally administered cephalosporins
10. Patients using supplements containing antioxidants as vitamins C or E

Primary outcomes:
measure: To assess the effect of high dose NAC (1800 mg)on small airways by measuring the total and peripheral airway resistance calculated with CFD
timeFrame: at baseline, after 12 weeks of placebo and after 12 weeks of NAC
measure: 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
timeFrame: at baseline, after 12 weeks of placebo and after 12 weeks of NAC.
Secondary outcomes:
measure: To assess dynamic and static lung volumes by spirometry, body plethysmography and diffusion
timeFrame: will be assessed at all visits
measure: To assess quality of life by the SGRQ
timeFrame: will be assessed at all visits
measure: To assess the tolerability and safety of high dose NAC
timeFrame: all visits
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: University Hospital Antwerp
state: Antwerp
Study officials:
affiliation: University Hospital, Antwerp
name: Wilfried A De Backer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Backer J, Vos W, Van Holsbeke C, Vinchurkar S, Claes R, Parizel PM, De Backer W. Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients. Int J Chron Obstruct Pulmon Dis. 2013;8:569-79. doi: 10.2147/COPD.S49307. Epub 2013 Nov 22.