Cystic FibrosisNCT00531882
Pilot Mouthwash Study of Pioglitazone and Simvastatin in Healthy Volunteers
A study testing Pioglitazone, Simvastatin and Ibuprofen in people with Cystic Fibrosis, run by University Hospitals Cleveland Medical Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Pioglitazone, Simvastatin and Ibuprofen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2007to Feb 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- ≥ 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University Hospitals of Cleveland
Cleveland, Ohio, 44106
About this study
Official title: 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.
Read the 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).
- Conditions
- Cystic Fibrosis
- Being tested
- Pioglitazone, Simvastatin, Ibuprofen
- Keywords
- healthy volunteers, neutrophil migration, anti inflammatory non-steroidal agent, simvastatin, pioglitazone
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called ACTOS
30 mg once a day
SimvastatinDrug
Also called Zocor
40 mg once a day
IbuprofenDrug
Also called Motrin
Ibuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day
| Study group | Role | What they receive |
|---|---|---|
| 1-pioglitazone | Experimental | Pioglitazone Receives: Drug: Pioglitazone |
| 2-simvasatin | Experimental | Simvastatin Receives: Drug: Simvastatin |
| 3-Ibuprofen 1000-1600 mg/day | Active comparator | Ibuprofen 1000-16-- mg/day, maximum 3200 mg/day Receives: Drug: Ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3X Before treatment (Days 1,2,3) 3X During treatment (Days 8,9,10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael W. Konstan, University Hospitals Cleveland Medical Center
- Investigators
- Michael W Konstan, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00531882
- Sponsor's protocol ID
- Pilot Healthy Volunteers
- Status last verified
- Sep 2017
- First submitted
- 18 Sep 2007
- Last updated
- 5 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Evaluating the Effect of Pioglitazone, Simvastatin, and Ibuprofen on Neutrophil Migration in Vivo in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00531882
- Acronym / sponsor ID
- Pilot Healthy Volunteers
- Conditions
- Cystic Fibrosis
- Keywords
- healthy volunteers, neutrophil migration, anti inflammatory non-steroidal agent, simvastatin, pioglitazone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 19 Sep 2007 (estimated)
- Results
- Posted 28 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1-pioglitazone | Experimental | Drug: PioglitazonePioglitazone |
| 2-simvasatin | Experimental | Drug: SimvastatinSimvastatin |
| 3-Ibuprofen 1000-1600 mg/day | Active comparator | Drug: IbuprofenIbuprofen 1000-16-- mg/day, maximum 3200 mg/day |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- ≥ 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: ACTOS30 mg once a day | Drug | 1-pioglitazone |
| SimvastatinAlso: Zocor40 mg once a day | Drug | 2-simvasatin |
| IbuprofenAlso: MotrinIbuprofen 15-23 mg/kg twice daily, maximum 3200 mg/day | Drug | 3-Ibuprofen 1000-1600 mg/day |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael W Konstan, MD principal investigator
University Hospitals Cleveland Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pioglitazone, Simvastatin and Ibuprofen in people with Cystic Fibrosis, run by University Hospitals Cleveland Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2017.