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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
COPD	Drug: N-acetylcysteine; Drug: placebo	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	12 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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 Start Date :	March 2009
Actual Primary Completion Date :	January 2011
Actual Study Completion Date :	January 2011

Arms and Interventions

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

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. To assess the effect of high dose NAC (1800 mg)on small airways by measuring the total and peripheral airway resistance calculated with CFD [ Time Frame: at baseline, after 12 weeks of placebo and after 12 weeks of NAC ]
2. 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 [ Time Frame: at baseline, after 12 weeks of placebo and after 12 weeks of NAC. ]

Secondary Outcome Measures :

1. To assess dynamic and static lung volumes by spirometry, body plethysmography and diffusion [ Time Frame: will be assessed at all visits ]
2. To assess quality of life by the SGRQ [ Time Frame: will be assessed at all visits ]
3. To assess the tolerability and safety of high dose NAC [ Time Frame: all visits ]

Eligibility Criteria

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Ages Eligible for Study:	40 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

Belgium
University Hospital Antwerp
Edegem, Antwerp, Belgium, 2650

Sponsors and Collaborators

University Hospital, Antwerp

Investigators

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

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Wilfried De Backer, MD PhD, University Hospital, Antwerp
ClinicalTrials.gov Identifier:	NCT00969904 History of Changes
Other Study ID Numbers:	PML_DOC_0804; EC 8/40/128
First Posted:	September 1, 2009
Last Update Posted:	July 3, 2012
Last Verified:	June 2012

Additional relevant MeSH terms:

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents	Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes