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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: N-acetylcysteine (NAC)

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama At Birmingham
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Denver, Colorado, United States
      • National Jewish Hospital
  • Connecticut
    • New Haven, Connecticut, United States
      • Yale New Haven Hospital
  • Florida
    • Gainesville, Florida, United States
      • Shands at the University of Florida
  • New York
    • New York, New York, United States
      • Columbia University Medical Ctr
  • North Carolina
    • Durham, North Carolina, United States
      • Duke Children
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • The PennState Milton S Hersey Medical Ctr
    • Philadelphia, Pennsylvania, United States
      • The Children
    • Pittsburg, Pennsylvania, United States
      • Children
  • Utah
    • Salt Lake City, Utah, United States
      • University of Utah, Primary Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: PharmaNAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum	(change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group)	From enrollment to end of the 24-week trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FEV1 (Percent of Predicted for Age)	Change in forced expiratory volume in 1 second as compared to normals for age (percent of predicted)	From enrollment to the end of the 24-week trial
FEV1 (L)	Forced expiratory volume in 1 second (Liters)	Baseline to end of study (24 weeks)
FEF 25-75% (L/Sec)	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.	Baseline to end of study (24 weeks)
FEF 25-75% (Percent of Predicted)	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).	Baseline to 24 weeks

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Carol K. Conrad, Stanford University

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: December 15, 2008
• First Submitted That Met QC Criteria: December 15, 2008
• First Posted (Estimate): December 17, 2008

Study Record Updates

• Last Update Posted (Estimate): April 22, 2013
• Last Update Submitted That Met QC Criteria: April 15, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Inflammation; Pneumonia; Cystic Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: SU-12112008-1378