Assessment of Inflammatory Mediators (AIM)

December 18, 2007 updated by: Ramsey, Bonnie, MD

Assessment of Induced Sputum as a Tool to Evaluate Anti-Inflammatory Agents in Patients With Cystic Fibrosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
(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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ramsey, Bonnie, MD

Collaborators

Cystic Fibrosis Foundation

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2004

Study Completion (Actual)

March 1, 2006

Study Registration Dates

First Submitted

September 16, 2005

First Submitted That Met QC Criteria

September 16, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Estimate)

December 25, 2007

Last Update Submitted That Met QC Criteria

December 18, 2007

Last Verified

August 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CFOM0003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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