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Assessment of Inflammatory Mediators (AIM)

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ibuprofen
Sponsored by
Ramsey, Bonnie, MD
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, Anti-inflammatory Agents, Ibuprofen

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Stanford University - Packard Children's Hospital
  • University of California - San Diego
  • University of Colorado Health Sciences Center - Children's Hospital
  • University of Iowa
  • Johns Hopkins Hospital
  • Massachusetts General Hospital
  • Harvard University - Children's Hospital of Boston, Pulmonary Division
  • University Of Minnesota
  • Washington University - St. Louis Children's Hospital
  • University of North Carolina, Chapel Hill
  • Cincinnati Children's Hospital Medical Center
  • Case Western Reserve University - Rainbow Babies and Children's Hospital
  • Columbus Children's Hospital
  • Baylor College of Medicine - Texas Children's Hospital
  • University of Utah Health Sciences Center

Outcomes

Primary Outcome Measures

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) 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

Full Information

First Posted
September 16, 2005
Last Updated
December 18, 2007
Sponsor
Ramsey, Bonnie, MD
Collaborators
Cystic Fibrosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00219895
Brief Title
Assessment of Inflammatory Mediators (AIM)
Official Title
Assessment of Induced Sputum as a Tool to Evaluate Anti-Inflammatory Agents in Patients With Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2006
Overall Recruitment Status
Completed
Study Start Date
August 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Ramsey, Bonnie, MD
Collaborators
Cystic Fibrosis Foundation

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, Anti-inflammatory Agents, Ibuprofen

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Primary Outcome Measure Information:
Title
Changes in markers of inflammation in induced sputum samples: total white cell count, total neutrophil count, percent neutrophils, active elastase, and cytokines.
Secondary Outcome Measure Information:
Title
(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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Chmiel, MD, MPH
Organizational Affiliation
Case Western Reserve University - Rainbow Babies and Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35223
Country
United States
Facility Name
Stanford University - Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of Colorado Health Sciences Center - Children's Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Harvard University - Children's Hospital of Boston, Pulmonary Division
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University Of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University - St. Louis Children's Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of North Carolina, Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Case Western Reserve University - Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Columbus Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205-2696
Country
United States
Facility Name
Baylor College of Medicine - Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health Sciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

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Assessment of Inflammatory Mediators (AIM)

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