Assessment of Inflammatory Mediators (AIM)

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00219895
• Other study ID #: CFOM0003
• Status: Completed
• Phase: N/A
• First received: September 16, 2005
• Last updated: December 18, 2007
• Start date: August 2004
• Est. completion date: March 2006

Study information

• Verified date: August 2006
• Source: Ramsey, Bonnie, MD
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Ibuprofen

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Harvard University - Children's Hospital of Boston, Pulmonary Division	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University - Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	University of Colorado Health Sciences Center - Children's Hospital	Denver	Colorado
United States	Baylor College of Medicine - Texas Children's Hospital	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Stanford University - Packard Children's Hospital	Palo Alto	California
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	University of California - San Diego	San Diego	California
United States	Washington University - St. Louis Children's Hospital	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Ramsey, Bonnie, MD	Cystic Fibrosis Foundation Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in markers of inflammation in induced sputum samples: total white cell count, total neutrophil count, percent neutrophils, active elastase, and cytokines.
Secondary	(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