Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers

NCT00531882 | Completed Results

• 1 other identifier: Pilot Healthy Volunteers
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Cystic Fibrosis

Keywords

healthy volunteers; neutrophil migration; anti inflammatory non-steroidal agent; simvastatin; pioglitazone

Outcome Measures

Primary Outcomes (1)

• Neutrophil Delivery to the Oral Mucosa Using a Non-invasive Mouthwash Technique

  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)

Study Arms (3)

1-pioglitazone

EXPERIMENTAL

Pioglitazone

Drug: Pioglitazone

2-simvasatin

EXPERIMENTAL

Simvastatin

Drug: Simvastatin

3-Ibuprofen 1000-1600 mg/day

ACTIVE COMPARATOR

Ibuprofen 1000-16-- mg/day, maximum 3200 mg/day

Drug: Ibuprofen

Interventions

Pioglitazone DRUG

30 mg once a day

Also known as: ACTOS

1-pioglitazone

Simvastatin DRUG

40 mg once a day

Also known as: Zocor

2-simvasatin

Ibuprofen DRUG

Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day

Also known as: Motrin

3-Ibuprofen 1000-1600 mg/day

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead

Study Sites (2)

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Pioglitazone; Simvastatin; Ibuprofen

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Michael W Konstan, MD
• Organization: University Hospitals Case Medical Center

michael.konstan@uhhospitals.org

2168445267

Study Officials

• Michael W Konstan, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No person associated with the study was masked
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman Department of Pediatrics

Study Record Dates

• First Submitted: September 18, 2007
• First Posted: September 19, 2007
• Study Start: September 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: October 5, 2017
• Results First Posted: July 28, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)