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

NCT00809094 | Completed Phase 2 Results

• 1 other identifier: SU-12112008-1378
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 11

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Change in FEV1 (Percent of Predicted for Age)

  From enrollment to the end of the 24-week trial

• FEV1 (L)

  Baseline to end of study (24 weeks)

• FEF 25-75% (L/Sec)

  Baseline to end of study (24 weeks)

• FEF 25-75% (Percent of Predicted)

  Baseline to 24 weeks

Other Outcomes (2)

• Change in DLCO (ml/Min/mmHg) Over Time by Treatment Group

  Baseline to 24 weeks

• Change in ECHO Tricuspid Regurgitation (mm Hg) Over Time by Treatment Group

  Baseline to 24 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo was administered oral tablet TID for 24 weeks.

Drug: Placebo

N-Acetylcysteine

ACTIVE COMPARATOR

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

Drug: N-acetylcysteine (NAC)

Interventions

N-acetylcysteine (NAC) DRUG

Also known as: PharmaNAC

N-Acetylcysteine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

National Jewish Hospital

Denver, Colorado, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, United States

Location

Shands at the University of Florida

Gainesville, Florida, United States

Location

Columbia University Medical Ctr

New York, New York, United States

Location

Duke Children

Durham, North Carolina, United States

Location

The PennState Milton S Hersey Medical Ctr

Hershey, Pennsylvania, United States

Location

The Children

Philadelphia, Pennsylvania, United States

Location

Children

Pittsburgh, Pennsylvania, United States

Location

University of Utah, Primary Children

Salt Lake City, Utah, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Carol Conrad
• Organization: Stanford University

cconrad@stanford.edu

650-723-8325

Study Officials

• Carol K. Conrad

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2008
• First Posted: December 17, 2008
• Study Start: November 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: April 22, 2013
• Results First Posted: March 15, 2013

Record last verified: 2013-04

Locations

US (11)