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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00809094
• Other study ID #: SU-12112008-1378
• Status: Completed
• Phase: Phase 2
• First received: December 15, 2008
• Last updated: April 15, 2013
• Start date: November 2008
• Est. completion date: February 2011

Study information

• Verified date: April 2013
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pneumonia

Intervention

Drug:
• N-acetylcysteine (NAC)

• Placebo

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Cystic Fibrosis Foundation Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Other	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	Yes
Primary	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	No
Secondary	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	No
Secondary	FEV1 (L)	Forced expiratory volume in 1 second (Liters)	Baseline to end of study (24 weeks)	No
Secondary	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)	No
Secondary	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	No