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Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00531882
Recruitment Status : Completed
First Posted : September 19, 2007
Results First Posted : July 28, 2017
Last Update Posted : October 5, 2017
Information provided by (Responsible Party):
Michael W. Konstan, University Hospitals Cleveland Medical Center

Brief Summary:

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. However, utilization of this valuable drug has been suboptimal because of its rare, but dramatic, adverse effects. 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. The investigators have shown, in our preliminary studies, that high dose ibuprofen limits the delivery of neutrophils to an inflamed mucosal surface, the gingival crevices. The investigators 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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Pioglitazone Drug: Simvastatin Drug: Ibuprofen Not Applicable

Detailed Description:
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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: No person associated with the study was masked
Primary Purpose: Other
Official Title: A Pilot Study Evaluating the Effect of Pioglitazone, Simvastatin, and Ibuprofen on Neutrophil Migration in Vivo in Healthy Subjects
Study Start Date : September 2007
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

Arm Intervention/treatment
Experimental: 1-pioglitazone
Drug: Pioglitazone
30 mg once a day
Other Name: ACTOS

Experimental: 2-simvasatin
Drug: Simvastatin
40 mg once a day
Other Name: Zocor

Active Comparator: 3-Ibuprofen 1000-1600 mg/day
Ibuprofen 1000-16-- mg/day, maximum 3200 mg/day
Drug: Ibuprofen
Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day
Other Name: Motrin

Primary Outcome Measures :
  1. Neutrophil Delivery to the Oral Mucosa Using a Non-invasive Mouthwash Technique [ Time Frame: 3X Before treatment (Days 1,2,3) 3X During treatment (Days 8,9,10) ]
    Oral mucosal polymorphonuclear leukocytes (PMN) are obtained and assessed using a modification of the mouthwash method of (Wright Blood 1986;67:1023-30). For each subject, PMN counts are assessed on days 1, 2, 3 [Baseline (B)]; days 8, 9, 10 [Treatment (T)]; and days 11, 13, 15 [Recovery (R)]. The PMN counts for each subject are averaged for each study time period (B, T or R) within each study arm (Pioglitazone, Simvastatin and Ibuprofen). The mean baseline (B) PMN counts are compared to the mean treatment (T) PMN counts for each study arm, with the results expressed as the percent change in PMN counts . Paired T-tests between baseline and treatment PMN counts are used to analyze for significance. The recovery period is used to verify that the PMN counts return to baseline following the treatment period. Data from the recovery period is not shown.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00531882

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United States, Ohio
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
University Hospitals Cleveland Medical Center
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Principal Investigator: Michael W Konstan, MD University Hospitals Cleveland Medical Center
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Responsible Party: Michael W. Konstan, Chairman Department of Pediatrics, University Hospitals Cleveland Medical Center Identifier: NCT00531882    
Other Study ID Numbers: Pilot Healthy Volunteers
First Posted: September 19, 2007    Key Record Dates
Results First Posted: July 28, 2017
Last Update Posted: October 5, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Michael W. Konstan, University Hospitals Cleveland Medical Center:
healthy volunteers
neutrophil migration
anti inflammatory non-steroidal agent
Additional relevant MeSH terms:
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Cystic Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
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
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypoglycemic Agents