Assessment of Inflammatory Mediators (AIM)

• ClinicalTrials.gov Identifier: NCT00219895
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Last Update Posted: December 25, 2007
• Sponsor: Ramsey, Bonnie, MD
• Collaborator: Cystic Fibrosis Foundation
• Information provided by: Ramsey, Bonnie, MD

Study Description

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

• 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

Outcome Measures

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

• Ages Eligible for Study: 10 Years and older (Child, Adult, Older Adult)
• 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

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

Investigators

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

More Information

• ClinicalTrials.gov Identifier: NCT00219895
• 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:

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