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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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
N-acetylcysteine (NAC)
Placebo
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

7 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Stanford University School of Medicine
  • National Jewish Hospital
  • Yale New Haven Hospital
  • Shands at the University of Florida
  • Columbia University Medical Ctr
  • Duke Children
  • The PennState Milton S Hersey Medical Ctr
  • The Children
  • Children
  • University of Utah, Primary Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

N-Acetylcysteine

Arm Description

Placebo was administered oral tablet TID for 24 weeks.

Participants received 900 mg of oral N-acetylcysteine TID for 24 weeks.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)
FEV1 (L)
Forced expiratory volume in 1 second (Liters)
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.
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).

Full Information

First Posted
December 15, 2008
Last Updated
April 15, 2013
Sponsor
Stanford University
Collaborators
Cystic Fibrosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00809094
Brief Title
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

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Cystic Fibrosis Foundation

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was administered oral tablet TID for 24 weeks.
Arm Title
N-Acetylcysteine
Arm Type
Active Comparator
Arm Description
Participants received 900 mg of oral N-acetylcysteine TID for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine (NAC)
Other Intervention Name(s)
PharmaNAC
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum
Description
(change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group)
Time Frame
From enrollment to end of the 24-week trial
Secondary Outcome Measure Information:
Title
Change in FEV1 (Percent of Predicted for Age)
Description
Change in forced expiratory volume in 1 second as compared to normals for age (percent of predicted)
Time Frame
From enrollment to the end of the 24-week trial
Title
FEV1 (L)
Description
Forced expiratory volume in 1 second (Liters)
Time Frame
Baseline to end of study (24 weeks)
Title
FEF 25-75% (L/Sec)
Description
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.
Time Frame
Baseline to end of study (24 weeks)
Title
FEF 25-75% (Percent of Predicted)
Description
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).
Time Frame
Baseline to 24 weeks
Other Pre-specified Outcome Measures:
Title
Change in DLCO (ml/Min/mmHg) Over Time by Treatment Group
Description
Change in the diffusing capacity of carbon monoxide across the lung measured from baseline to end of 24-week study.
Time Frame
Baseline to 24 weeks
Title
Change in ECHO Tricuspid Regurgitation (mm Hg) Over Time by Treatment Group
Description
Change in measure of estimated right ventricular pressure over the 24-week study period
Time Frame
Baseline to 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female 7 years of age or older Diagnosis of CF based upon the following criteria: One or more clinical features characteristic of CF AND (b or c) Positive sweat test > 60 mEq/L by quantitative pilocarpine iontophoresis A genotype with two identifiable mutations consistent with CF Written informed consent (and assent when applicable) obtained from subject or subject's legal representative Clinically stable with no evidence of acute upper or lower respiratory tract infection within 4 weeks prior to enrollment 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 Able to tolerate sputum induction with 3% hypertonic saline and to expectorate Able to perform repeatable, consistent efforts in pulmonary function testing Weight > or = 25 kg at time of enrollment Females of child bearing potential must be willing to use birth control (IUD, oral, transdermal, or parenteral contraceptives; abstinence) Exclusion Criteria: Clinically significant liver enzymes (AST, ALT or GGT) > 2.5 times the upper limit of normal at screening History of ABPA, unless have evidence of a stable IgE (< 5% increase compared to previous test) for 6 months prior to enrollment Current or history of rheumatic or collagen vascular disorders Use of NSAIDS other than for chronic therapy within 1 week prior to enrollment Initiation of chronic therapy with ibuprofen, azithromycin, TOBI® or Aztreonam within 6 weeks prior to enrollment Consumption or inhalation of antioxidants (including NAC, GSH, Immunocal, Nacystelyn, pentoxyfilline) within 6 weeks prior to enrollment Use of oral or IV corticosteroids within 4 weeks prior to enrollment Use of acetaminophen within 3 days prior to enrollment 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 Known hypersensitivity to oral PharmaNAC® Current cigarette consumption Pregnant or breastfeeding Subject unlikely to complete the study as determined by the Investigator 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 Participation in trials for other anti-inflammatory or therapeutic investigational drugs within 6 weeks prior to enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carol K. Conrad
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
National Jewish Hospital
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
Shands at the University of Florida
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
Columbia University Medical Ctr
City
New York
State/Province
New York
Country
United States
Facility Name
Duke Children
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
The PennState Milton S Hersey Medical Ctr
City
Hershey
State/Province
Pennsylvania
Country
United States
Facility Name
The Children
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Children
City
Pittsburg
State/Province
Pennsylvania
Country
United States
Facility Name
University of Utah, Primary Children
City
Salt Lake City
State/Province
Utah
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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