Official Title: “A Pilot Study Evaluating the Effect of Pioglitazone, Simvastatin, and Ibuprofen on Neutrophil Migration in Vivo in Healthy Subjects”

Inflammation clearly contributes to the progression of the cystic fibrosis (CF) lung disease, and administration of the anti-inflammatory agent high-dose ibuprofen retards the rate of decline of pulmonary function (1). However, utilization of this valuable drug has been suboptimal because of its rare, but dramatic, adverse effects (2). Therefore, alternative anti-inflammatory agents are urgently needed. One strategy for identifying new anti-inflammatory agents is to determine the mechanism by which the only proven anti-inflammatory agent for the CF lung disease, high-dose ibuprofen, exerts its effect. If this were known, then other drugs that act by a similar mechanism become candidates for treating the CF inflammatory disease. We have shown, in our preliminary studies, that high dose ibuprofen limits the delivery of neutrophils to an inflamed mucosal surface, the gingival crevices. We plan to test pioglitazone and simvastatin, (ibuprofen (positive control)) to determine their anti inflammatory affects on neutrophil migration to the oral mucosa.

The hypothesis to be tested is that pioglitazone, and/or simvastatin will reduce neutrophils in the oral mucosa after 10 days of therapy in mouthwashes of healthy volunteers. Ibuprofen will be used as a positive control.

This study will provide pilot data from healthy volunteers to support an FDA Grant to be submitted at a future date.

Study Type: Interventional

Study Design: Other, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Eligibility Criteria Inclusion Criteria - ≥ 18 < 50 years of age - Healthy volunteers must be in general good health as determined by a medical history. - Ability to understand and sign the informed consent form - Ability to adhere to the protocol. - Willing to use an acceptable form of birth control

Exclusion Criteria - History of diabetes requiring insulin - The use of NSAIDS (ibuprofen) or corticosteroids including inhaled steroids. Nasal steroids are acceptable. - The use of statin lowering medications - Active gingival disease (Active tooth or gum disease) - Any chronic inflammatory condition that immuno compromises the volunteer as determined by medical history. - Pregnant or planning to become pregnant

The entire study period for each subject will be 15 days, and consist of 3 periods defined as: Baseline (Day 1,2,3), Treatment (Day 3-10), and Recovery (Day 13-15). Healthy volunteers will be screened on Day 1 (and assessed for eligibility); Eligible subjects will be divided into 3 drug treatment groups pioglitazone, simvastatin and ibuprofen the positive control.

The two treatment groups will consist of 4 healthy volunteers who meet the inclusion criteria. There will be 2 healthy volunteers in the positive control group. Group 1 will receive pioglitazone 30 mg once daily, Group 2 will receive simvastatin 40 mg daily and Group 3 the positive control will receive ibuprofen (15-23 mg/kg twice daily, maximum 3200 mg/day) during the Treatment period and serve as the positive control group. This dose is 25% of that prescribed to CF patients. As healthy volunteers are recruited, the first will be assigned to Group 1, the second to Group 2, and so on. After the third subject has been assigned to Group 3, this pattern of assignment will be repeated with subjects 4, 5 and 6, The following 4 healthy volunteers will be assigned to group 1 and 2 (7, 8, 9, 10).

Primary:

• neutrophil delivery to the oral mucosa using a noninvasive mouth wash technique 3x before treatment, 3x during treatment and 3x post treatment

Inclusion Criteria:

• ≥ 18 < 50 years of age
• Healthy volunteers must be in general good health as determined by a medical history.
• Ability to understand and sign the informed consent form
• Ability to adhere to the protocol.
• Willing to use an acceptable form of birth control

Exclusion Criteria:

• History of diabetes requiring insulin
• The use of NSAIDS (ibuprofen) or corticosteroids including inhaled steroids. Nasal steroids are acceptable.
• The use of statin lowering medications
• Active gingival disease (Active tooth or gum disease)
• Any chronic inflammatory condition that immuno compromises the volunteer as determined by medical history.
• Pregnant or planning to become pregnant

Lead Sponsor: University Hospitals of Cleveland

University Hospitals of Cleveland

Cleveland Ohio 44106 United States

Overall Clinical Trial Officials and Contacts

Michael W Konstan, MD Principal Investigator University Hospitals of Cleveland  

Overall Contact: Kathleen A Hilliard, BA, CCRC 216.844.7489 kathleen.hilliard@case.edu

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00531882

Study ID Number: Pilot Healthy Volunteers

ClinicalTrials.gov Identifier: NCT00531882

Health Authority: United States: Institutional Review Board