EmphysemaPhase 2PIENCT02006576
Prostaglandin Inhibition for Emphysema
A Phase 2 study testing 600 mg ibuprofen three times daily for 48 weeks in people with Emphysema, run by University of Nebraska at 5 sites in United States.
Trial summary
The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower respiratory tract and if this results in improvement in measures of lung repair function. Read more about this study
- Who is it for?
- Ages 46 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Emphysema
- What is being tested?
- 600 mg ibuprofen three times daily for 48 weeks
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 5 sitesUnited States
- Study dates
- 1 Jan 2014to 31 Mar 2018
- Phase
- Phase 2
- 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 46 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 45 years
- Emphysema (>5% of voxels <950 Hounsfield Units determined on the CT scan performed as part of the COPDGene study as quantified at the COPDGene radiology center). An equivalent scan as determined by the radiology center is also acceptable.
- Post-bronchodilator FEV1 > 35% predicted)
- Smoker or ex-smoker (10 pack years minimum)
Who cannot join
- Contraindication to bronchoscopy or other study procedures
- Pregnancy of plans to become pregnant within six months
- Aspirin-sensitive asthma
- Regular use of systemic glucocorticoid
- Regular use of an NSAID (low dose aspirin for cardiac disease is acceptable and subjects taking only this regularly will be eligible)
- Unstable medical condition
Show all 11Show fewer
- History of myocardial infarction or unstable angina within six months
- Allergy to or history of adverse effect from ibuprofen or other NSAID
- History of gastrointestinal bleeding within one year
- Any condition that, in the opinion of the investigator, places the subject at untoward risk
- Inability to provide informed consent
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
National Jewish Health
Denver, Colorado, 80206
Univerisity of Nebraska Medical Center
Omaha, Nebraska, 68105
Temple University
Philadelphia, Pennsylvania, 19140
Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: Proof-of-concept Study to Demonstrate Inhibition of Prostaglandin E (PGE) Production and Associated Biological Effects in the Lower Respiratory Tract by Ibuprofen.
The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower respiratory tract and if this results in improvement in measures of lung repair function.
Read the detailed description
The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower respiratory tract and if this results in improvement in measures of lung repair function. This is a proof-of-concept study. The PIE study will set the stage for novel therapy to modify the course of chronic obstructive pulmonary disease (COPD).
COPD is the third leading cause of death in the United States. No currently available treatment can meaningfully restore lung function that is lost in this disease. Emphysema is a major component of COPD and results when lung damage exceeds the ability of the lung to repair. Recent evidence indicates that the repair processes present in the normal lung are deficient in patients with emphysema and that this is due, in part, to suppression of repair by an inflammatory mediator: prostaglandin E (PGE). Currently available therapies can block PGE production, but whether this can be achieved in the lung in COPD is unknown. The PIE study will answer that question.
This will be accomplished by performing a randomized, double blind, placebo-controlled, parallel group study that will compare a widely used and well-tolerated non-steroidal anti-inflammatory drug, ibuprofen 600 mg three times daily, with placebo. PGE will be measured directly in the lower respiratory tract by sampling the lung with the technique of bronchoalveolar lavage. Secondary measures will be made, quantifying PGE in induced sputum and quantifying PGE metabolites in blood and urine. In addition, the current proposal will determine if biochemical measures of lung repair are restored by treatments that block PGE production. Additional outcomes will also be assessed including the effect of treatment on PGD and other eicosanoids and assessing IL-8 and neutrophils in sputum and BAL fluid and selected inflammatory biomarkers present in serum that may be associated with lung function decline. Finally, in an accompanying Ancillary Study, the current proposal will determine if alveolar macrophages over-produce PGE and/or PGD in COPD and will determine if the microRNA miR-146a modulates the production of these prostaglandins, as we have demonstrated for lung fibroblasts. The Ancillary Study will also determine if genetic variation in a miR-146a is related to differential expression.
The proposed research will, therefore, determine if inhibition of PGE production can be achieved in the lung, if this appears to restore lung repair mechanisms and will help determine who would benefit from such a therapeutic approach. This is a highly novel approach to the treatment of emphysema and has the potential to restore lost lung function, a crucial unmet medical need for a major public health problem.
- Conditions
- Emphysema
- Being tested
- 600 mg ibuprofen three times daily for 48 weeks, Placebo three times daily
- Keywords
- Emphysema, Prostaglandin E, Bronchoalveolar lavage
- Medical subject headings
- Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
600 mg ibuprofen three times daily for 48 weeksDrug
Also called Advil, Children's Ibuprofen, Advil Migraine, Motrin IB, NeoProfen, Caldolor, Wal-Profen, I-Prin
Placebo three times dailyOther
| Study group | Role | What they receive |
|---|---|---|
| COPD, Placebo | Placebo comparator | Placebo three times daily Receives: Other: Placebo three times daily |
| Control subject | No intervention | Control subjects, no intervention |
| COPD, ibuprofen | Experimental | 600 mg ibuprofen three times daily for 48 weeks Receives: Drug: 600 mg ibuprofen three times daily for 48 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Will Ibuprofen, 600 mg Three Times Daily, Decrease PGE Concentration in the Alveolar Portion of BAL Fluid in Subjects With Emphysema in Comparison to Placebo?
PGE will be measured by HPLC in alveolar fluids obtained at randomization (week 0) and again 12 weeks after randomization on emphysema subjects taking placebo and emphysema subjects taking ibuprofen to compare control group versus treatment group.
Measured: 12 weeks after subject randomization
Secondary outcomes (1)
Will Ibuprofen, 600 mg Three Times Daily, Increase Pro-collagen Peptide Fragment Concentrations in the Alveolar Portion of BAL Fluid in Subjects With Emphysema in Comparison to Placebo?
Pro-collagen peptide fragments will be measured by ELISA in alveolar fluids obtained at randomization (week 0) and again 12 weeks after randomization on emphysema subjects taking placebo and emphysema subjects taking ibuprofen to compare control group versus treatment group.
Measured: 12 weeks after subject randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2013 (estimated)
- Study start1 Jan 2014
- Primary completion31 Mar 2018
- Study completion31 Mar 2018
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 EmphysemaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Jewish Health, Temple University, University of California, Los Angeles, University of Alabama at Birmingham
- Responsible party
- Sponsor
- Investigators
- Stephen I Rennard, MD, Study chair, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02006576
- Sponsor's protocol ID
- 0503-13-ET
- Acronym
- PIE
- Status last verified
- Nov 2023
- First submitted
- 4 Dec 2013
- Last updated
- 13 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof-of-concept Study to Demonstrate Inhibition of Prostaglandin E (PGE) Production and Associated Biological Effects in the Lower Respiratory Tract by Ibuprofen.
- ClinicalTrials.gov ID
- NCT02006576
- Acronym / sponsor ID
- PIE / 0503-13-ET
- Conditions
- Emphysema
- Keywords
- Emphysema, Prostaglandin E, Bronchoalveolar lavage
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Jewish Health, Temple University, University of California, Los Angeles, University of Alabama at Birmingham
- Study start
- 1 Jan 2014 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 10 Dec 2013 (estimated)
- Results
- Posted 16 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower respiratory tract and if this results in improvement in measures of lung repair function.
Detailed description
The Prostaglandin Inhibition for Emphysema (PIE) study will determine if a currently available therapy, ibuprofen 600 mg three times daily, can block PGE production in the lower respiratory tract and if this results in improvement in measures of lung repair function. This is a proof-of-concept study. The PIE study will set the stage for novel therapy to modify the course of chronic obstructive pulmonary disease (COPD).
COPD is the third leading cause of death in the United States. No currently available treatment can meaningfully restore lung function that is lost in this disease. Emphysema is a major component of COPD and results when lung damage exceeds the ability of the lung to repair. Recent evidence indicates that the repair processes present in the normal lung are deficient in patients with emphysema and that this is due, in part, to suppression of repair by an inflammatory mediator: prostaglandin E (PGE). Currently available therapies can block PGE production, but whether this can be achieved in the lung in COPD is unknown. The PIE study will answer that question.
This will be accomplished by performing a randomized, double blind, placebo-controlled, parallel group study that will compare a widely used and well-tolerated non-steroidal anti-inflammatory drug, ibuprofen 600 mg three times daily, with placebo. PGE will be measured directly in the lower respiratory tract by sampling the lung with the technique of bronchoalveolar lavage. Secondary measures will be made, quantifying PGE in induced sputum and quantifying PGE metabolites in blood and urine. In addition, the current proposal will determine if biochemical measures of lung repair are restored by treatments that block PGE production. Additional outcomes will also be assessed including the effect of treatment on PGD and other eicosanoids and assessing IL-8 and neutrophils in sputum and BAL fluid and selected inflammatory biomarkers present in serum that may be associated with lung function decline. Finally, in an accompanying Ancillary Study, the current proposal will determine if alveolar macrophages over-produce PGE and/or PGD in COPD and will determine if the microRNA miR-146a modulates the production of these prostaglandins, as we have demonstrated for lung fibroblasts. The Ancillary Study will also determine if genetic variation in a miR-146a is related to differential expression.
The proposed research will, therefore, determine if inhibition of PGE production can be achieved in the lung, if this appears to restore lung repair mechanisms and will help determine who would benefit from such a therapeutic approach. This is a highly novel approach to the treatment of emphysema and has the potential to restore lost lung function, a crucial unmet medical need for a major public health problem.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| COPD, Placebo | Placebo comparator | Other: Placebo three times dailyPlacebo three times daily |
| Control subject | No intervention | –Control subjects, no intervention |
| COPD, ibuprofen | Experimental | Drug: 600 mg ibuprofen three times daily for 48 weeks600 mg ibuprofen three times daily for 48 weeks |
Who may qualify
- Ages
- 46 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age > 45 years
- Emphysema (>5% of voxels <950 Hounsfield Units determined on the CT scan performed as part of the COPDGene study as quantified at the COPDGene radiology center). An equivalent scan as determined by the radiology center is also acceptable.
- Post-bronchodilator FEV1 > 35% predicted)
- Smoker or ex-smoker (10 pack years minimum)
Key exclusion criteria (11 listed)
- Contraindication to bronchoscopy or other study procedures
- Pregnancy of plans to become pregnant within six months
- Aspirin-sensitive asthma
- Regular use of systemic glucocorticoid
- Regular use of an NSAID (low dose aspirin for cardiac disease is acceptable and subjects taking only this regularly will be eligible)
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 |
|---|---|---|
| 600 mg ibuprofen three times daily for 48 weeksAlso: Advil, Children's Ibuprofen, Advil Migraine, Motrin IB, NeoProfen, Caldolor, Wal-Profen, I-Prin | Drug | COPD, ibuprofen |
| Placebo three times daily | Other | COPD, Placebo |
Primary outcome
Will Ibuprofen, 600 mg Three Times Daily, Decrease PGE Concentration in the Alveolar Portion of BAL Fluid in Subjects With Emphysema in Comparison to Placebo?
Time frame: 12 weeks after subject randomization
PGE will be measured by HPLC in alveolar fluids obtained at randomization (week 0) and again 12 weeks after randomization on emphysema subjects taking placebo and emphysema subjects taking ibuprofen to compare control group versus treatment group.
1 secondary outcome
Will Ibuprofen, 600 mg Three Times Daily, Increase Pro-collagen Peptide Fragment Concentrations in the Alveolar Portion of BAL Fluid in Subjects With Emphysema in Comparison to Placebo?
Time frame: 12 weeks after subject randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Stephen I Rennard, MD study chair
University of Nebraska
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 600 mg ibuprofen three times daily for 48 weeks in people with Emphysema, run by University of Nebraska at 5 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 4 inclusion and 11 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 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2019). 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?
Will Ibuprofen, 600 mg Three Times Daily, Decrease PGE Concentration in the Alveolar Portion of BAL Fluid in Subjects With Emphysema in Comparison to Placebo? (time frame: 12 weeks after subject randomization). 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 13 Dec 2023.