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

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.

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: N-acetylcysteine; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • University Hospital Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Wilfried A De Backer, MD, PhD, University Hospital, Antwerp

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: August 31, 2009
• First Submitted That Met QC Criteria: August 31, 2009
• First Posted (Estimate): September 1, 2009

Study Record Updates

• Last Update Posted (Estimate): July 3, 2012
• Last Update Submitted That Met QC Criteria: June 29, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: PML_DOC_0804; EC 8/40/128