Clinical trial NCT01739790: N-Acetylcysteine for Patients With COPD and Chronic Bronchitis
Official title: Effects of High-Dose N-Acetylcysteine on Respiratory Health Status in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis: A Randomized, Placebo-Controlled Trial-3
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: COPD
Chronic Bronchitis
Keywords: COPD
Chronic Bronchitis
N-acetylcysteine
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2012-12-03
Enrollment: 51
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: N-acetylcysteine (NAC) is described as having mucolytic and antioxidant properties. It is widely prescribed for patients with chronic obstructive lung disease (COPD), particularly for those who have accompanying symptoms of chronic cough and sputum production. Compared to placebo, high-dose NAC will improve Saint George Respiratory Questionnaire scores in patients with COPD and chronic bronchitis.

Detailed description: A total of 130 subjects with COPD and chronic bronchitis will be randomized (in a double-blind fashion) to receive either high-dose NAC (1800 mg) or matching placebo twice daily for eight weeks. Respiratory health status, assessed by changes in St. George's Respiratory Questionnaire, will be used to determine the effects of NAC on lung function. It is anticipated that the subjects on high dose NAC will have improved scores.

Eligibility criteria: Inclusion Criteria:

* Capability to provide written informed consent
* Age ≥ 40 years and ≤ 85 years
* FEV1/FVC ratio (post bronchodilator) \< 70%
* FEV1 (post bronchodilator) \< 65%
* Presence of chronic cough and sputum production defined as the following:
* Presence of chronic cough and sputum will be defined by responses to the first two questions on the SGRQ. Subjects who respond positively to both question 1 (cough) and question 2 (sputum) on the SGRQ as either "several days per week" or "almost every day" will be eligible
* Current or former smoker with lifetime cigarette consumption of at least 10 pack-years
* Negative serum pregnancy test at the baseline visit if patient is a pre-menopausal female (menopause defined as absence of a menstrual cycle in the last 12 months)
* Must be fluent in speaking the English language

Exclusion Criteria:

* Not fully recovered for at least 30 days from a COPD exacerbation characterized by typical symptoms and treated with antibiotics or prednisone
* Known allergy or sensitivity to NAC or albuterol
* Any patient with unstable cardiac disease
* Any patient with a documented history of uncompensated congestive heart failure in the last 2 years
* Clinical diagnosis of asthma, bronchiectasis, cystic fibrosis, or severe alpha-1 antitrypsin deficiency
* Active lung cancer or history of lung cancer if it has been less than 2 years since lung resection or other treatment. If history of lung cancer, must have no evidence of recurrence in the 2 years preceding the baseline visit.
* Undergoing active treatment for malignancy except for hormonal therapy (i.e. prostate cancer, breast cancer) or non-metastatic skin cancer and are not symptomatic
* Chronic kidney disease with an estimated GFR of \< 30 ml/min. GFR will be estimated using the Modification of Diet in Renal Disease (MDRD) formula
* History of cirrhosis with evidence of portal hypertension (ascites, chronic edema)
* Participation in a pulmonary rehabilitation program or completion within past 6 weeks
* Prisoners or institutionalized patients
* Participation in another study involving an investigational product within 30 days of the baseline visit
* Pregnant or breast-feeding patients.
* Use of guaifenesin in the last 30 days
* Currently on long acting nitrates for angina or heart failure
* Abnormalities in screening blood work defined as:
* WBC \< 3.0 or \> 15.0 K/cmm
* Hemoglobin \< 9.0 or \> 17.0 gm/dl
* Platelets \< 75 or \> 400 K/cmm
* ALT \> 3 times the upper limit of normal
* INR \> 1.5 unless on warfarin therapy
* Any concomitant condition that might endanger the patient through participation in the study or interfere with study procedures, as assessed by the investigator

Primary outcomes:
measure: Changes in the Saint George's Respiratory Questionnaire
timeFrame: Baseline to 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Dennis E Niewoehner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnson K, McEvoy CE, Naqvi S, Wendt C, Reilkoff RA, Kunisaki KM, Wetherbee EE, Nelson D, Tirouvanziam R, Niewoehner DE. High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial. Int J Chron Obstruct Pulmon Dis. 2016 Apr 21;11:799-807. doi: 10.2147/COPD.S102375. eCollection 2016.