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

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT00809094
First received: December 15, 2008
Last updated: April 15, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Cystic Fibrosis
Drug: N-acetylcysteine (NAC)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    (change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group)


Secondary Outcome Measures:
  • Change in FEV1 (Percent of Predicted for Age) [ Time Frame: From enrollment to the end of the 24-week trial ] [ Designated as safety issue: No ]
    Change in forced expiratory volume in 1 second as compared to normals for age (percent of predicted)

  • FEV1 (L) [ Time Frame: Baseline to end of study (24 weeks) ] [ Designated as safety issue: No ]
    Forced expiratory volume in 1 second (Liters)

  • FEF 25-75% (L/Sec) [ Time Frame: Baseline to end of study (24 weeks) ] [ Designated as safety issue: No ]
    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.

  • FEF 25-75% (Percent of Predicted) [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    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:
  • Change in DLCO (ml/Min/mmHg) Over Time by Treatment Group [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: Yes ]
    Change in the diffusing capacity of carbon monoxide across the lung measured from baseline to end of 24-week study.

  • Change in ECHO Tricuspid Regurgitation (mm Hg) Over Time by Treatment Group [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: Yes ]
    Change in measure of estimated right ventricular pressure over the 24-week study period


Enrollment: 70
Study Start Date: November 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809094

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

No publications provided

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT00809094     History of Changes
Other Study ID Numbers: SU-12112008-1378
Study First Received: December 15, 2008
Results First Received: February 14, 2013
Last Updated: April 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Inflammation
Pneumonia
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Respiratory Tract Infections
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on August 19, 2014