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

COPD Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00969904
• Other study ID #: PML_DOC_0804
• Secondary ID: EC 8/40/128
• Status: Completed
• Phase: Phase 4
• First received: August 31, 2009
• Last updated: June 29, 2012
• Start date: March 2009
• Est. completion date: January 2011

Study information

• Verified date: June 2012
• Source: University Hospital, Antwerp
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• COPD
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• N-acetylcysteine
600 mg TID for 12 weeks
• placebo
placebo tablet TID for 12 weeks

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Edegem	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Antwerp

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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.	No
Secondary	To assess dynamic and static lung volumes by spirometry, body plethysmography and diffusion		will be assessed at all visits	No
Secondary	To assess quality of life by the SGRQ		will be assessed at all visits	No
Secondary	To assess the tolerability and safety of high dose NAC		all visits	Yes