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

Purpose

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	Intervention	Phase
COPD	Drug: N-acetylcysteine Drug: placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (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.

Resource links provided by NLM:

Drug Information available for: Acetylcysteine

U.S. FDA Resources

Further study details as provided by Wilfried De Backer, University Hospital, Antwerp:

Primary Outcome Measures:

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 ]
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:

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


Enrollment:	12
Study Start Date:	March 2009
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1	Drug: N-acetylcysteine 600 mg TID for 12 weeks
Placebo Comparator: 2	Drug: placebo placebo tablet TID for 12 weeks

Eligibility


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

Criteria

Inclusion Criteria:

Patients with documented COPD based on the following criteria:
- Smoking history of at least 10 pack-years
- Decreased Tiffeneau index (FEV1/(FVC < 0.70)
Patients aged ≥ 40 years
Patients who stopped smoking since more than 1 month
Patients who present moderate COPD with an FEV1 between 50 and 80% of predicted (GOLD 2)
Patients should be treated according to GOLD guidelines

Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00969904

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

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
Study First Received:	August 31, 2009
Last Updated:	June 29, 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

ClinicalTrials.gov processed this record on May 25, 2017