Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis
Study type: Interventional

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.
    

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).
    

Intervention name(s): Pioglitazone; Simvastatin; Ibuprofen
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 30 mg once a day; 40 mg once a day; Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day
Other intervention name(s): ACTOS; Zocor; Motrin
Intervention MeSH terms: Pioglitazone; Ibuprofen; Simvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: healthy volunteers; neutrophil migration; anti inflammatory non-steroidal agent; simvastatin; pioglitazone