Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in People With Idiopathic Pulmonary Fibrosis

Official Title: “Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in IPF”

Idiopathic pulmonary fibrosis (IPF) is a long-term lung disease that affects an individual's ability to breathe. This study will evaluate the effectiveness of the antioxidant N-acetylcysteine (NAC), at preventing the loss of lung function in people with IPF.

IPF is a disease in which fibrous tissue clogs and damages the air sacs within the lungs.

Widespread and permanent scarring and stiffening of lung tissue eventually results.

Individuals with IPF may experience breathing difficulties, cough, chest pain, and a decreased exercise capacity. Although the cause of IPF is not definitively known, it may be a result of an inflammatory response to an unknown substance. There is no cure for IPF, and no approved treatment for the disease. NAC, an antioxidant that is effective at loosening up mucus that forms in the lungs, may improve lung function. The purpose of this study is to evaluate the effectiveness of NAC at preventing the loss of lung function in people with IPF.

This study will enroll people with mild to moderate IPF. Participants will be randomly assigned to receive for 60 weeks either NAC alone or placebo. Study visits will occur at baseline and Weeks 4, 15, 30, 45, and 60. At all study visits, a physical exam and blood collection will occur. At selected visits, the following study procedures will occur: lung function testing; urine collection; a 6-minute walk test, which will measure the distance walked in a 6-minute period; and questionnaires to assess health status, breathing, and quality of life. Participants will record medication usage and symptoms in a daily diary.

Study researchers will review medical records and the Social Security death index 5 years after the end of the study to determine the incidence of death among study participants.

Intervention(s) in this Clinical Trial

• Drug: N-acetylcysteine (NAC)
  • Participants will receive 600 mg of NAC three times a day.
• Drug: Placebo
  • Participants will receive placebo each day.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Participants will receive N-acetylcysteine (NAC) for 60 weeks.
• Placebo Comparator: 2
  • Participants will receive placebo for 60 weeks.

Primary Measures

• Change in serial forced vital capacity
  • Time Frame: Measured at Week 60
    Safety Issue?: No

Secondary Measures

• Time to disease progression
  • Time Frame: Measured at Week 60
    Safety Issue?: No
• Acute exacerbations
  • Time Frame: Measured at Week 60
    Safety Issue?: No
• Respiratory infections
  • Time Frame: Measured at Week 60
    Safety Issue?: No
• Maintained forced vital capacity response
  • Time Frame: Measured at Week 60
    Safety Issue?: No

Inclusion Criteria:

• Forced vital capacity (FVC) greater than or equal to 50% of predicted value
• Diffusion capacity (DLCO) greater than or equal to 30% of predicted value
• Diagnosis of IPF by modified American Thoracic Society (ATS) criteria in the 48 months before study entry

Exclusion Criteria:

• History of clinically significant environmental exposure known to cause pulmonary fibrosis
• Diagnosis of connective tissue disease as the likely cause of the interstitial disease
• Extent of emphysema greater than the extent of fibrotic change (i.e., honeycombing, reticular changes) on high resolution computed tomography (HRCT) scan
• Forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.65 at the time of screening (post-bronchodilator)
• Partial pressure of arterial oxygen (PaO2) less than 55 mm Hg (less than 50 mm Hg at
• Denver study site)
• Residual volume greater than 120% predicted at the time of screening (post-bronchodilator)
• Evidence of active infection
• Significant bronchodilator response on screening spirometry, defined as change in FEV1 greater than or equal to 12% and absolute change greater than 200 mL OR change in FVC greater than or equal to 12% and absolute change greater than 200 mL
• Screening and baseline FVC measurements (in liters, post-bronchodilator) differing by 11%
• Listed for lung transplantation
• History of unstable or deteriorating cardiac disease
• Heart attack, coronary artery bypass, or angioplasty in the 6 months before study entry
• Unstable angina pectoris or congestive heart failure requiring hospitalization in the 6 months before study entry
• Uncontrolled arrhythmia
• Severe uncontrolled high blood pressure
• Known HIV or hepatitis C
• Known cirrhosis and chronic active hepatitis
• Active substance and/or alcohol abuse
• Pregnant or breastfeeding
• Women of childbearing potential who are not using a medically approved means of contraception
• Any clinically relevant lab abnormalities, including the following:
• 1. Creatinine greater than twice the upper limit of normal (ULN)
• 2. Hematology outside of specified limits
• 1. White blood cells less than 3,500/mm3
• 2. Hematocrit less than 25% or greater than 59%
• 3. Platelets less than 100,000 mm3 at the time of screening
• 3. Any of the following liver function test criteria above specified limits
• 1. Total bilirubin greater than twice the ULN
• 2. Aspartate (AST) or alanine aminotransferases (ALT) greater than 1.5 the ULN
• 3. Alkaline phosphatase greater than three times the ULN
• 4. Albumin less than 3.0 mg/dL at the time of screening
• Known hypersensitivity to study medication
• Any condition other than IPF that, in the opinion of the site PI, is likely to result in death in the 1 year after study entry
• Any condition that, in the judgment of the PI, might cause participation in this study to be detrimental or makes the person a poor candidate for the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Heart, Lung, and Blood Institute (NHLBI) NIH

Overall Clinical Trial Officials and Contacts

Marvin I Schwarz, MD Study Chair University of Colorado, Denver  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00650091

Study ID Number: 506

ClinicalTrials.gov Identifier: NCT00650091

Health Authority: United States: Food and Drug Administration

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