Clinical trial NCT00809094: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2008-12-17
Enrollment: 70
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum
timeFrame: From enrollment to end of the 24-week trial
Secondary outcomes:
measure: Change in FEV1 (Percent of Predicted for Age)
timeFrame: From enrollment to the end of the 24-week trial
measure: FEV1 (L)
timeFrame: Baseline to end of study (24 weeks)
measure: FEF 25-75% (L/Sec)
timeFrame: Baseline to end of study (24 weeks)
measure: FEF 25-75% (Percent of Predicted)
timeFrame: Baseline to 24 weeks
Other outcomes:
measure: Change in DLCO (ml/Min/mmHg) Over Time by Treatment Group
timeFrame: Baseline to 24 weeks
measure: Change in ECHO Tricuspid Regurgitation (mm Hg) Over Time by Treatment Group
timeFrame: Baseline to 24 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Denver
country: United States
facility: National Jewish Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: Shands at the University of Florida
state: Florida
city: New York
country: United States
facility: Columbia University Medical Ctr
state: New York
city: Durham
country: United States
facility: Duke Children
state: North Carolina
city: Hershey
country: United States
facility: The PennState Milton S Hersey Medical Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children
state: Pennsylvania
city: Pittsburg
country: United States
facility: Children
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah, Primary Children
state: Utah
Study officials:
affiliation: Stanford University
name: Carol K. Conrad
role: PRINCIPAL_INVESTIGATOR
References: