Assessment of Inflammatory Mediators (AIM)

Study Description

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Brief Summary:

Specific Aim: To determine whether neutrophils, active elastase, and cytokines measured in sputum induced using hypertonic saline are useful screening tests for determining if a particular agent with known anti-inflammatory properties is a suitable candidate for more extensive clinical trials in patients with CF. This aim will be addressed using an anti-inflammatory agent, ibuprofen, that has been shown to have clinical benefit in CF. A "no treatment" arm will be included as the control group.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Ibuprofen	Not Applicable

Detailed Description:

Inflammation clearly contributes to the progression of cystic fibrosis (CF) lung disease. Anti-inflammatory therapy with alternate-day corticosteroids and twice-daily high-dose ibuprofen in patients with CF has shown clinical benefit, but adverse effects and other considerations have markedly limited their use. Therefore, alternative anti-inflammatory agents are urgently needed. Results from the clinical trials of alternate-day corticosteroids and high-dose ibuprofen in CF indicate that anti-inflammatory therapy will probably not result in improvement in pulmonary function, but will slow the rate of decline. This expectation imposes constraints on the design of studies to test new anti-inflammatory agents, requiring that they use many patients over a considerable period of time (years, rather than the months that are necessary to evaluate anti-infective or anti-obstructive therapies). Thus, it is highly desirable to design a strategy for evaluation of prospective anti-inflammatory agents that will allow for the selection of only the most promising agents for further study in Phase III type trials. Of additional concern is the fact that some pharmaceutical firms have not pursued development of anti-inflammatory agents for CF because there were no early indicators of efficacy. This presents an insurmountable hurdle for translation of research advances into clinical treatments. Some means of screening candidate drugs is urgently required. This study will assess the measurement of inflammatory mediators in induced sputum as one such strategy. The hypothesis to be tested is that ibuprofen will reduce neutrophils, active elastase, and pro-inflammatory cytokines in induced sputum after 4 weeks of therapy in patients with CF.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	120 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Assessment of Induced Sputum as a Tool to Evaluate Anti-Inflammatory Agents in Patients With Cystic Fibrosis
Study Start Date :	August 2004
Actual Study Completion Date :	March 2006

Arms and Interventions

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Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Changes in markers of inflammation in induced sputum samples: total white cell count, total neutrophil count, percent neutrophils, active elastase, and cytokines.

Secondary Outcome Measures :

1. (1) Alterations in laboratory evaluations: CBC, ESR, CRP, serum chemistry profile, urinalysis, and spirometry. (2) Adverse events associated with sputum induction or administration of study medications

Eligibility Criteria

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Ages Eligible for Study:	10 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male or female 10 years of age or older.

• Confirmed diagnosis of CF based on the following criteria:

  • positive sweat chloride >= 60 mEq/liter (by pilocarpine iontophoresis) and/or
  • a genotype with two identifiable mutations consistent with CF, and
  • accompanied by one or more clinical features consistent with the CF phenotype
• FEV1 >= 50% predicted value (subjects >= 10 - <18 years of age) or >= 40% predicted value (subjects >= 18 years of age)
• Clinically stable with no evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to Visit 1 (Day 0)
• Ability to reproducibly perform spirometry and peak flow measurements
• Ability to understand and sign a written informed consent or assent and comply with the requirements of the study

Exclusion Criteria:

• Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
• Chronic daily use of ibuprofen, celecoxib, or other selective COX-2 inhibitors, other NSAIDs, or systemic or inhaled corticosteroids within the 4 weeks prior to Visit 1 (Day 0) or acute usage within 72 hours prior to Visit 1 (Day 0)
• History of hypersensitivity to beta-agonists
• History of hypersensitivity to sulfonamides, aspirin, or other NSAIDs
• Oxygen saturation < 92% on room air at Visit 1 (Day 0)
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• History of hemoptysis >= 30 cc per episode during the 30 days prior to Visit 1 (Day 0)
• Significant history of hepatic, cardiovascular, renal, neurological, hematologic, or peptic ulcer disease
• SGOT (ALT) or SGPT (AST) > 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension
• Creatinine > 1.8 mg/dL at screening
• Inability to swallow pills
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data

Contacts and Locations

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Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35223
United States, California
Stanford University - Packard Children's Hospital
Palo Alto, California, United States, 94304
University of California - San Diego
San Diego, California, United States, 92123
United States, Colorado
University of Colorado Health Sciences Center - Children's Hospital
Denver, Colorado, United States, 80218
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Harvard University - Children's Hospital of Boston, Pulmonary Division
Boston, Massachusetts, United States, 02115
United States, Minnesota
University Of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University - St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
United States, North Carolina
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Case Western Reserve University - Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
United States, Texas
Baylor College of Medicine - Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Sciences Center
Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Ramsey, Bonnie, MD

Cystic Fibrosis Foundation Therapeutics

Investigators

Principal Investigator:	James Chmiel, MD, MPH	Case Western Reserve University - Rainbow Babies and Children's Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

ClinicalTrials.gov Identifier:	NCT00219895 History of Changes
Other Study ID Numbers:	CFOM0003
First Posted:	September 22, 2005
Last Update Posted:	December 25, 2007
Last Verified:	August 2006

Keywords provided by Ramsey, Bonnie, MD:

Cystic Fibrosis; Anti-inflammatory Agents; Ibuprofen

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Ibuprofen; Anti-Inflammatory Agents	Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action