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), alone and in combination with an established IPF medication regimen, at preventing the loss of lung function in people with IPF.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

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, but most people with the disease take prednisone, a corticosteroid medication that helps reduce inflammation, and azathioprine, a medication with immune-suppression properties to slow the fibrous growth and scar forming process. NAC, an antioxidant that is effective at loosening up mucus that forms in the lungs, may improve lung function. Adding NAC to the standard treatment regimen of prednisone and azathioprine may be beneficial to people with IPF. The purpose of this study is to evaluate the effectiveness of NAC, alone and in combination with prednisone and azathioprine, 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 combination treatment with prednisone, azathioprine, and NAC; NAC alone; or placebo. Study visits will occur at baseline and Weeks 4, 12, 24, 36, 48, 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.

Primary:

• Change in serial forced vital capacity Measured at Week 60 No

Secondary:

• Time to disease progression Measured at Week 60 No
• Acute exacerbations Measured at Week 60 No
• Respiratory infections Measured at Week 60 No
• Maintained forced vital capacity response Measured at Week 60 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
• Homozygous for low thiopurine S-methyl transferase (TPMT)
• Uncontrolled depression (Hospital Anxiety and Depression [HAD] score greater than or equal to 15)
• 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

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

University of Alabama - Birmingham

Birmingham Alabama 35294 United States

University of California - Los Angeles

Los Angeles California 90095 United States

University of California - San Francisco

San Francisco California 94110 United States

National Jewish Medical and Research Center

Denver Colorado 80206 United States

Emory University

Atlanta Georgia 30322 United States

University of Chicago

Chicago Illinois 60637 United States

Tulane University

New Orleans Louisiana 70118 United States

University of Michigan

Ann Arbor Michigan 48109 United States

Mayo Clinic

Rochester Minnesota 55905 United States

Weill Medical College of Cornell University

New York New York 10021 United States

Vanderbilt University

Nashville Tennessee 37232 United States

University of Washington

Seattle Washington 98165 United States

Overall Clinical Trial Officials and Contacts

Gary Hunninghake, MD Study Chair University of Iowa  

Information obtained from ClinicalTrials.gov on July 23, 2008

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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