Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers

September 6, 2017 updated by: Michael W. Konstan, University Hospitals Cleveland Medical Center

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. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

25

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
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Children's Hospital

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

14 years to 46 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1-pioglitazone
Pioglitazone
Drug: Pioglitazone
30 mg once a day
Other Names:
  • ACTOS
Experimental: 2-simvasatin
Simvastatin
Drug: Simvastatin
40 mg once a day
Other Names:
  • 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 Names:
  • Motrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 et.al. 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.
3X Before treatment (Days 1,2,3) 3X During treatment (Days 8,9,10)

Collaborators and Investigators

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

Sponsor

University Hospitals Cleveland Medical Center

Investigators

  • Principal Investigator: Michael W Konstan, MD, University Hospitals Cleveland Medical Center

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

September 1, 2007

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

September 18, 2007

First Submitted That Met QC Criteria

September 18, 2007

First Posted (Estimate)

September 19, 2007

Study Record Updates

Last Update Posted (Actual)

October 5, 2017

Last Update Submitted That Met QC Criteria

September 6, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pilot Healthy Volunteers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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