Trial Outcomes & Findings for Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers (NCT NCT00531882)

NCT ID: NCT00531882

Last Updated: 2017-10-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

25 participants

Primary outcome timeframe

3X Before treatment (Days 1,2,3) 3X During treatment (Days 8,9,10)

Results posted on

2017-10-05

Participant Flow

Subjects were recruited from lab personnel and CF Center employees and UH employees and by word of mouth. Due to the vulnerability of this population every effort was made to avoid coercion. No one was enrolled that was directly supervised by the PI. The recruitment log was kept in a secure location in the CF Team Office.

Inclusion and exclusion criteria were reviewed at screening. Concomitant medications were reviewed prior to randomization. Subjects were excluded if they were on NSAIDS, corticosteroids (including inhaled steroids and statin lowering medications.

Participant milestones

Participant milestones
Measure
1-Pioglitazone
Pioglitazone Pioglitazone: 30 mg once a day pioglitazone (Actos, Takeda) will be administered orally in a dose of 30 mg once daily. This is the highest recommended dose for initial control of type II diabetes.
2-Simvastatin
Simvastatin (Zocor): 40 mg once a day will be administered orally in a dose of 49 mg once daily to all subjects. This dose is considered a mid-level adult dose and the maximum pediatric dose recommended for hyperlipidemia.
3-Ibuprofen 1000-1600 mg Twice Daily (Max 3200 mg/Day)
Ibuprofen will be used as the positive control for this study. Ibuprofen (Motrin, Pharmacia) will be administered twice daily.
Overall Study
STARTED
10
10
5
Overall Study
COMPLETED
10
10
5
Overall Study
NOT COMPLETED
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
1-Pioglitazone
n=10 Participants
Pioglitazone Pioglitazone: 30 mg once a day
2-Simvastin
n=10 Participants
Simvastatin Simvastatin: 40 mg once a day
3-Ibuprofen 1000-1600 mg Twice Daily
n=5 Participants
Ibuprofen 1000-1600 mg twice daily (max 3200 mg/day)
Total
n=25 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
Age, Categorical
Between 18 and 65 years
10 Participants
n=93 Participants
10 Participants
n=4 Participants
5 Participants
n=27 Participants
25 Participants
n=483 Participants
Age, Categorical
>=65 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
Age, Continuous
29.4 years
STANDARD_DEVIATION 8.8 • n=93 Participants
28.8 years
STANDARD_DEVIATION 9.1 • n=4 Participants
24.5 years
STANDARD_DEVIATION 4.0 • n=27 Participants
27.6 years
STANDARD_DEVIATION 2.8 • n=483 Participants
Sex: Female, Male
Female
6 Participants
n=93 Participants
5 Participants
n=4 Participants
3 Participants
n=27 Participants
14 Participants
n=483 Participants
Sex: Female, Male
Male
4 Participants
n=93 Participants
5 Participants
n=4 Participants
2 Participants
n=27 Participants
11 Participants
n=483 Participants

PRIMARY outcome

Timeframe: 3X Before treatment (Days 1,2,3) 3X During treatment (Days 8,9,10)

Population: Healthy volunteers free of gingival disease were randomized 2:2:1 to oral Pioglitazone, Simvastatin or Ibuprofen respectively for 10 days.

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.

Outcome measures

Outcome measures
Measure
1-Pioglitazone
n=10 Participants
Pioglitazone Pioglitazone: 30 mg once a day
2-Simvastatin
n=10 Participants
Simvastatin Simvastatin: 40 mg once a day
3-Ibuprofen 1000-1600 mg Twice Daily (Max 3200 mg/Day)
n=5 Participants
Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day Ibuprofen: Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day
Neutrophil Delivery to the Oral Mucosa Using a Non-invasive Mouthwash Technique
6.4 % change in mean PMN counts: B vs T
-19.6 % change in mean PMN counts: B vs T
-28.4 % change in mean PMN counts: B vs T

Adverse Events

1-Pioglitazone

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

2-Simvastin

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

3-Ibuprofen 1000-1600 mg Twice Daily (Max 3200 mg/Day)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
1-Pioglitazone
n=10 participants at risk
Pioglitazone Pioglitazone: 30 mg once a day
2-Simvastin
n=10 participants at risk
Simvastatin Simvastatin: 40 mg once a day
3-Ibuprofen 1000-1600 mg Twice Daily (Max 3200 mg/Day)
n=5 participants at risk
Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day Ibuprofen: Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day
Musculoskeletal and connective tissue disorders
joint pain
0.00%
0/10 • Subjects were questioned and examined by the Investigator or his/her designee for evidence of adverse events. Subjects were monitored for the 15 days they participated in the study.
20.0%
2/10 • Number of events 2 • Subjects were questioned and examined by the Investigator or his/her designee for evidence of adverse events. Subjects were monitored for the 15 days they participated in the study.
0.00%
0/5 • Subjects were questioned and examined by the Investigator or his/her designee for evidence of adverse events. Subjects were monitored for the 15 days they participated in the study.

Additional Information

Michael W Konstan, MD

University Hospitals Case Medical Center

Phone: 2168445267

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place