NAC Phase IIB: A Multi-Center, Phase IIB, Randomized, Placebo-controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine On Redox Changes and Lung Inflammation In Cystic Fibrosis Patients

• ClinicalTrials.gov Identifier: NCT00809094
• Recruitment Status: Completed
• First Posted: December 17, 2008
• Results First Posted: March 15, 2013
• Last Update Posted: April 22, 2013
• Sponsor: Stanford University
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): Stanford University

Study Description

Brief Summary:

This Phase IIB proof-of-concept study would examine the effects of an investigational product called N-acetylcysteine (NAC) on the basic processes that cause inflammation in CF lung disease. We hope to learn more about the causes of lung disease in cystic fibrosis by studying the characteristics of the inflammation in the lungs of patients who have CF.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: N-acetylcysteine (NAC); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Phase IIB, Randomized, Placebo-controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine On Redox Changes and Lung Inflammation In Cystic Fibrosis Patients
• Study Start Date: November 2008
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo was administered oral tablet TID for 24 weeks.	Drug: Placebo
Active Comparator: N-Acetylcysteine; Participants received 900 mg of oral N-acetylcysteine TID for 24 weeks.	Drug: N-acetylcysteine (NAC); Other Name: PharmaNAC

Outcome Measures

Primary Outcome Measures :

1. Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum [ Time Frame: From enrollment to end of the 24-week trial ]
   (change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group)

Secondary Outcome Measures :

1. Change in FEV1 (Percent of Predicted for Age) [ Time Frame: From enrollment to the end of the 24-week trial ]
   Change in forced expiratory volume in 1 second as compared to normals for age (percent of predicted)
2. FEV1 (L) [ Time Frame: Baseline to end of study (24 weeks) ]
   Forced expiratory volume in 1 second (Liters)
3. FEF 25-75% (L/Sec) [ Time Frame: Baseline to end of study (24 weeks) ]
   Difference in mid-expiratory flow rates between 25 to 75% of the vital capacity, in L/sec measured at the beginning of the study to the end of the study.
4. FEF 25-75% (Percent of Predicted) [ Time Frame: Baseline to 24 weeks ]
   Difference in the forced expiratory flow rate in mid-exhalation as a percent of predicted to standard values measured from baseline to the end of study (24 weeks).

Other Outcome Measures:

1. Change in DLCO (ml/Min/mmHg) Over Time by Treatment Group [ Time Frame: Baseline to 24 weeks ]
   Change in the diffusing capacity of carbon monoxide across the lung measured from baseline to end of 24-week study.
2. Change in ECHO Tricuspid Regurgitation (mm Hg) Over Time by Treatment Group [ Time Frame: Baseline to 24 weeks ]
   Change in measure of estimated right ventricular pressure over the 24-week study period

Eligibility Criteria

• Ages Eligible for Study: 7 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female 7 years of age or older

2. Diagnosis of CF based upon the following criteria:

   1. One or more clinical features characteristic of CF AND (b or c)
   2. Positive sweat test > 60 mEq/L by quantitative pilocarpine iontophoresis
   3. A genotype with two identifiable mutations consistent with CF
3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative
4. Clinically stable with no evidence of acute upper or lower respiratory tract infection within 4 weeks prior to enrollment
5. Stable mild or moderately severe lung disease defined by an FEV1 > or = 40% and < or = 85% predicted for age based on the Wang (males < 18 years, females < 16 years) or Hankinson (males > or = 18 years, females > or = 16 years) standardized equations
6. Able to tolerate sputum induction with 3% hypertonic saline and to expectorate
7. Able to perform repeatable, consistent efforts in pulmonary function testing
8. Weight > or = 25 kg at time of enrollment
9. Females of child bearing potential must be willing to use birth control (IUD, oral, transdermal, or parenteral contraceptives; abstinence)

Exclusion Criteria:

1. Clinically significant liver enzymes (AST, ALT or GGT) > 2.5 times the upper limit of normal at screening
2. History of ABPA, unless have evidence of a stable IgE (< 5% increase compared to previous test) for 6 months prior to enrollment
3. Current or history of rheumatic or collagen vascular disorders
4. Use of NSAIDS other than for chronic therapy within 1 week prior to enrollment
5. Initiation of chronic therapy with ibuprofen, azithromycin, TOBI® or Aztreonam within 6 weeks prior to enrollment
6. Consumption or inhalation of antioxidants (including NAC, GSH, Immunocal, Nacystelyn, pentoxyfilline) within 6 weeks prior to enrollment
7. Use of oral or IV corticosteroids within 4 weeks prior to enrollment
8. Use of acetaminophen within 3 days prior to enrollment

9. Unable to forego during the study:

   • Vitamin E: more than 400 IU/day for subjects < or = 12 years of age and 800 IU/day for subjects > 12 years of age
   • Vitamin C: more than 0.5 gm/day
   • More than two alcoholic drinks per day
10. Known hypersensitivity to oral PharmaNAC®
11. Current cigarette consumption
12. Pregnant or breastfeeding
13. Subject unlikely to complete the study as determined by the Investigator
14. Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the subject
15. Participation in trials for other anti-inflammatory or therapeutic investigational drugs within 6 weeks prior to enrollment

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

United States, Colorado

National Jewish Hospital

Denver, Colorado, United States

United States, Connecticut

Yale New Haven Hospital

New Haven, Connecticut, United States

United States, Florida

Shands at the University of Florida

Gainesville, Florida, United States

United States, New York

Columbia University Medical Ctr

New York, New York, United States

United States, North Carolina

Duke Children

Durham, North Carolina, United States

United States, Pennsylvania

The PennState Milton S Hersey Medical Ctr

Hershey, Pennsylvania, United States

The Children

Philadelphia, Pennsylvania, United States

Children

Pittsburg, Pennsylvania, United States

United States, Utah

University of Utah, Primary Children

Salt Lake City, Utah, United States

Sponsors and Collaborators

Stanford University

Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Carol K. Conrad; Stanford University

More Information

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT00809094
• Other Study ID Numbers: SU-12112008-1378
• First Posted: December 17, 2008
• Results First Posted: March 15, 2013
• Last Update Posted: April 22, 2013
• Last Verified: April 2013

Additional relevant MeSH terms:

Pneumonia; Cystic Fibrosis; Fibrosis; Inflammation; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Respiratory Tract Infections; Infections; 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