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

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Placebo; Drug: N-acetylcysteine (NAC)

• Registration Number: NCT00809094
• Lead Sponsor: Stanford University

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2008-12-15
• Study First Submitted QC: 2008-12-15
• Study First Posted: 2008-12-17
• Primary Completion: 2011-02
• Study Completion: 2011-02
• Results First Submitted: 2013-02-14
• Results First Submitted QC: 2013-02-14
• Results First Posted: 2013-03-15
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-15
• Last Update Posted: 2013-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo was administered oral tablet TID for 24 weeks.
N-Acetylcysteine	N-acetylcysteine (NAC)	Participants received 900 mg of oral N-acetylcysteine TID for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum	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

Name	Time	Method
Change in FEV1 (Percent of Predicted for Age)	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)
FEV1 (L)	Baseline to end of study (24 weeks)	Forced expiratory volume in 1 second (Liters)
FEF 25-75% (L/Sec)	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.
FEF 25-75% (Percent of Predicted)	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).

Trial Locations

Locations (11)

National Jewish Hospital; 🇺🇸 Denver, Colorado, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States

Shands at the University of Florida; 🇺🇸 Gainesville, Florida, United States

The Children; 🇺🇸 Philadelphia, Pennsylvania, United States

The PennState Milton S Hersey Medical Ctr; 🇺🇸 Hershey, Pennsylvania, United States

Duke Children; 🇺🇸 Durham, North Carolina, United States

Columbia University Medical Ctr; 🇺🇸 New York, New York, United States

Children; 🇺🇸 Pittsburg, Pennsylvania, United States

University of Utah, Primary Children; 🇺🇸 Salt Lake City, Utah, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States