Severe, Refractory AsthmaPhase 2NCT00994175
A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
A Phase 2 study testing Pioglitazone in people with Severe, Refractory Asthma and Airway Inflammation, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
Trial summary
Background: Individuals who have severe asthma that is not easily controlled by current treatments are in need of new treatments to prevent potentially life-threatening asthma attacks. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Severe, Refractory Asthma, Airway Inflammation, Airflow Obstruction
- What is being tested?
- Pioglitazone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Sep 2009to 24 Jun 2016
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be between 18 and 75 years of age, male or female, with a diagnosis of severe, refractory asthma, as defined by the American Thoracic Society, for at least one year.
- Subjects must have a history of reversible airflow obstruction as defined by a positive methacholine bronchoprovocation challenge or a positive response to inhaled bronchodilators at some point in the course of their disease or a greater than 20% variability in the Forced Expiratory Volume in 1 second (FEV1) or the peak expiratory flow (PEF) documented during serial measurements of lung function over time.
- Left ventricular ejection fraction greater than or equal to 50% by echocardiogram
- For women of childbearing potential, negative pregnancy test prior to study and willingness to adhere to reliable birth control methods during the study.
- Subjects must have the ability to provide informed consent
Who cannot join
- A known history of hypersensitivity to pioglitazone.
- Asthma exacerbation requiring treatment with additional oral corticosteroids in the previous 6 weeks, or a life-threatening asthma attack requiring cardiopulmonary support in the previous 6 months.
- Cigarette smoking within the previous 12 months or a prior history of > 20 cumulative pack-years.
- Investigational therapy for any indication within I month prior to the screening visit.
- History of lung disease other than asthma (ie., COPD, sarcoidosis).
- History of diabetes mellitus requiring treatment with any medication, insulin secreting tumor, or symptomatic hypoglycemia.
Show all 35Show fewer
- HIV/AIDS
- History of congestive heart failure with current symptoms consistent with NYHA classification II, Ill or IV.
- Preexisting edema (2+ or greater).
- Hemoglobin < 11 gm/dl for males and < 10 gm/dl for females.
- Active liver disease or abnormal liver function tests > 2 times upper limit of normal.
- History of bladder or colon cancer.
- History of other cancer not in remission.
- Active breast feeding.
- Use of the following medications, which can interact with pioglitazone:
- Gemfibrizol (Lopid)
- Atazanivir (Reyataz)
- Ritonavir (Norvir)
- Rifampin (Rifadpin)
- Carbamzepine (Tegretol)
- Phenobarbital (Luminal)
- Phenytoin (Dilantin)
- Rifapentine (Priftin)
- Secobarbital (Seconal)
- Amiodarone (Cordarone, Pacerone)
- Palitaxel (Taxol)
- Replaglinide (Prandine)
- Ketoconazole (Nizoral)
- Atorvastatin (Lipitor )
- Fosphenytoin (Cerebyx)
- Itraconazole (Sporanox)
- Trimethoprim (in Bactrim)
- Thioridazine
- Certain over-the-counter herbs and supplements. These will be reviewed by the investigators for possible interactions with the study medication A determination of whether the supplement is safe to use with pioglitazone will be made on a case-by-case basis.
- Any condition that, in the investigator s opinion, places the patient at undue risk for complications from pioglitazone therapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
INOVA Fairfax Hospital
Falls Church, Virginia, 22042
About this study
Background:
- Individuals who have severe asthma that is not easily controlled by current treatments are in need of new treatments to prevent potentially life-threatening asthma attacks. Experiments in mice have found that a medication called pioglitazone hydrochloride (Actos ), which is used to treat patients with diabetes, may be effective for treating severe asthma. Researchers are interested in determining whether Actos is effective in improving the quality of life in subjects with severe asthma who continue to have symptoms despite maximum standard medical therapy.
Read more
Objectives:
- To assess the effectiveness of pioglitazone hydrochloride as a treatment for patients with severe asthma that is not controlled by standard treatments.
Eligibility:
- Individuals between 18 and 75 years of age who have been diagnosed with and treated for severe asthma for at least 1 year.
Design:
- Potential participants will have a screening visit to determine eligibility for the study. The visit will involve breathing tests, chest x rays, heart and lung monitoring, and blood tests.
- Eligible participants will have a full medical history and will answer a series of questionnaires about their quality of life with asthma.
- Phase 1: Patients will record lung function and asthma symptoms morning and evening for 4 weeks. At the end of this period, patients will be evaluated with breathing, allergy, and blood tests, as well as questionnaires. Patients will also provide a sputum sample.
- Phase 2: Patients will receive regular doses of either pioglitazone hydrochloride or a placebo for 16 weeks. Patients will return to the National Institutes of Health every 4 weeks for tests.
- Phase 3: Wash-out period without study drugs for 4 weeks, similar to Phase 1.
- Phase 4: Patients will receive regular doses of either pioglitazone hydrochloride or a placebo for 16 weeks. Patients who received placebo will be given the study drug, and vice versa. Patients will return to the National Institutes of Health every 4 weeks for tests.
- Phase 5: Medications will be stopped, and patients will return to the National Institutes of Health 4 weeks later for final tests.
Read the detailed description
New therapies are needed for patients with asthma who are sub-optimally controlled by standard measures. Pioglitazone hydrochloride (Actos ) is a highly selective and potent agonist for the peroxisome proliferator-activated receptor-Gamma (PPAR Gamma). Studies in murine models of allergic asthma have shown that PPAR Gamma agonists down-regulate allergen-mediated airway inflammation and airway hyperresponsiveness. This protocol is a randomized, placebo-controlled, doubleblind, crossover (phase II) pilot study of the efficacy of pioglitazone for the treatment of patients with severe, refractory asthma. The primary end-point for this study will be quality of life as determined by the Asthma Quality of Life Questionnaire (AQLQ) score. Secondary end-points will include indices of airway inflammation, airflow obstruction, airway hyperreactivity, and asthma symptoms.
- Being tested
- Pioglitazone, Placebo
- Keywords
- Pioglitazone, Severe, Refractory Asthma, Peroxisome Proliferator-Activated Receptor Gamma, Airflow Obstruction, Airway Inflammation, Asthma
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone, Then Placebo | Experimental | Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the first treatment phase, followed by 45 mg daily for an additional 14 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the placebo phase for 16 weeks in the second treatment phase to receive the placebo. Receives: Drug: Pioglitazone; Drug: Placebo |
| Placebo, Then Pioglitazone | Experimental | Placebo was administered for 16 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the Pioglitazone treatment group. Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the treatment phase, followed by 45 mg daily for an additional 14 weeks. Receives: Drug: Pioglitazone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score
Juniper Asthma Quality of Life Questionnaire (AQLQ) score at the end of the pioglitazone treatment period as compared to the placebo treatment period. The AQLQ is scored on a 7-point scale with 7 = not impaired at all, 1 = severly impaired
Measured: 16 weeks
Baseline - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score
Juniper Asthma Quality of Life Questionnaire (AQLQ) score at the end of the pioglitazone treatment period as compared to the placebo treatment period. The AQLQ is scored on a 7-point scale with 7 = not impaired at all, 1 = severly impaired
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2009 (estimated)
- Study start23 Sep 2009
- Primary completion24 Jun 2016
- Study completion24 Jun 2016
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Severe, Refractory AsthmaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stewart J Levine, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00994175
- Sponsor's protocol ID
- 090244
- Other IDs
- 09-H-0244
- Status last verified
- Aug 2017
- First submitted
- 10 Oct 2009
- Last updated
- 5 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The NIH Biomedical Translational Research Information System
Publications
Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541. No abstract available.
PubMed 16236742Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE, Green RH, Bradding P, Brightling CE, Wardlaw AJ, Pavord ID. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006 Feb 16;354(7):697-708. doi: 10.1056/NEJMoa050580.
PubMed 16481637Erin EM, Leaker BR, Nicholson GC, Tan AJ, Green LM, Neighbour H, Zacharasiewicz AS, Turner J, Barnathan ES, Kon OM, Barnes PJ, Hansel TT. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med. 2006 Oct 1;174(7):753-62. doi: 10.1164/rccm.200601-072OC. Epub 2006 Jul 13.
PubMed 16840747Kaler M, Barochia AV, Weir NA, Cuento RA, Stylianou M, Roth MJ, Filie AC, Vaughey EC, Nathan SD, Levine SJ. A randomized, placebo-controlled, double-blinded, crossover trial of pioglitazone for severe asthma. J Allergy Clin Immunol. 2017 Dec;140(6):1716-1718. doi: 10.1016/j.jaci.2017.05.033. Epub 2017 Jun 15.
PubMed 28625806
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
- ClinicalTrials.gov ID
- NCT00994175
- Acronym / sponsor ID
- 090244
- Keywords
- Pioglitazone, Severe, Refractory Asthma, Peroxisome Proliferator-Activated Receptor Gamma, Airflow Obstruction, Airway Inflammation, Asthma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 23 Sep 2009
- Primary completion
- 24 Jun 2016 (actual)
- Study completion
- 24 Jun 2016 (actual)
- First posted
- 14 Oct 2009 (estimated)
- Results
- Posted 5 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Individuals who have severe asthma that is not easily controlled by current treatments are in need of new treatments to prevent potentially life-threatening asthma attacks. Experiments in mice have found that a medication called pioglitazone hydrochloride (Actos ), which is used to treat patients with diabetes, may be effective for treating severe asthma. Researchers are interested in determining whether Actos is effective in improving the quality of life in subjects with severe asthma who continue to have symptoms despite maximum standard medical therapy.
Objectives:
- To assess the effectiveness of pioglitazone hydrochloride as a treatment for patients with severe asthma that is not controlled by standard treatments.
Eligibility:
- Individuals between 18 and 75 years of age who have been diagnosed with and treated for severe asthma for at least 1 year.
Design:
- Potential participants will have a screening visit to determine eligibility for the study. The visit will involve breathing tests, chest x rays, heart and lung monitoring, and blood tests.
- Eligible participants will have a full medical history and will answer a series of questionnaires about their quality of life with asthma.
- Phase 1: Patients will record lung function and asthma symptoms morning and evening for 4 weeks. At the end of this period, patients will be evaluated with breathing, allergy, and blood tests, as well as questionnaires. Patients will also provide a sputum sample.
- Phase 2: Patients will receive regular doses of either pioglitazone hydrochloride or a placebo for 16 weeks. Patients will return to the National Institutes of Health every 4 weeks for tests.
- Phase 3: Wash-out period without study drugs for 4 weeks, similar to Phase 1.
- Phase 4: Patients will receive regular doses of either pioglitazone hydrochloride or a placebo for 16 weeks. Patients who received placebo will be given the study drug, and vice versa. Patients will return to the National Institutes of Health every 4 weeks for tests.
- Phase 5: Medications will be stopped, and patients will return to the National Institutes of Health 4 weeks later for final tests.
Detailed description
New therapies are needed for patients with asthma who are sub-optimally controlled by standard measures. Pioglitazone hydrochloride (Actos ) is a highly selective and potent agonist for the peroxisome proliferator-activated receptor-Gamma (PPAR Gamma). Studies in murine models of allergic asthma have shown that PPAR Gamma agonists down-regulate allergen-mediated airway inflammation and airway hyperresponsiveness. This protocol is a randomized, placebo-controlled, doubleblind, crossover (phase II) pilot study of the efficacy of pioglitazone for the treatment of patients with severe, refractory asthma. The primary end-point for this study will be quality of life as determined by the Asthma Quality of Life Questionnaire (AQLQ) score. Secondary end-points will include indices of airway inflammation, airflow obstruction, airway hyperreactivity, and asthma symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone, Then Placebo | Experimental | Drug: Pioglitazone, Drug: PlaceboPioglitazone, 30 mg daily, was administered for the initial 2 weeks of the first treatment phase, followed by 45 mg daily for an additional 14 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the placebo phase for 16 weeks in the second treatment phase to receive the placebo. |
| Placebo, Then Pioglitazone | Experimental | Drug: Pioglitazone, Drug: PlaceboPlacebo was administered for 16 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the Pioglitazone treatment group. Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the treatment phase, followed by 45 mg daily for an additional 14 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects will be between 18 and 75 years of age, male or female, with a diagnosis of severe, refractory asthma, as defined by the American Thoracic Society, for at least one year.
- Subjects must have a history of reversible airflow obstruction as defined by a positive methacholine bronchoprovocation challenge or a positive response to inhaled bronchodilators at some point in the course of their disease or a greater than 20% variability in the Forced Expiratory Volume in 1 second (FEV1) or the peak expiratory flow (PEF) documented during serial measurements of lung function over time.
- Left ventricular ejection fraction greater than or equal to 50% by echocardiogram
- For women of childbearing potential, negative pregnancy test prior to study and willingness to adhere to reliable birth control methods during the study.
- Subjects must have the ability to provide informed consent
Key exclusion criteria (35 listed)
- A known history of hypersensitivity to pioglitazone.
- Asthma exacerbation requiring treatment with additional oral corticosteroids in the previous 6 weeks, or a life-threatening asthma attack requiring cardiopulmonary support in the previous 6 months.
- Cigarette smoking within the previous 12 months or a prior history of > 20 cumulative pack-years.
- Investigational therapy for any indication within I month prior to the screening visit.
- History of lung disease other than asthma (ie., COPD, sarcoidosis).
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 |
|---|---|---|
| Pioglitazone | Drug | Pioglitazone, Then Placebo, Placebo, Then Pioglitazone |
| Placebo | Drug | Pioglitazone, Then Placebo, Placebo, Then Pioglitazone |
Primary outcome
16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score
Time frame: 16 weeks
Juniper Asthma Quality of Life Questionnaire (AQLQ) score at the end of the pioglitazone treatment period as compared to the placebo treatment period. The AQLQ is scored on a 7-point scale with 7 = not impaired at all, 1 = severly impaired
Baseline - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score
Time frame: Baseline
Juniper Asthma Quality of Life Questionnaire (AQLQ) score at the end of the pioglitazone treatment period as compared to the placebo treatment period. The AQLQ is scored on a 7-point scale with 7 = not impaired at all, 1 = severly impaired
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16236742Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541. No abstract available.
- Background: PubMed 16481637Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE, Green RH, Bradding P, Brightling CE, Wardlaw AJ, Pavord ID. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006 Feb 16;354(7):697-708. doi: 10.1056/NEJMoa050580.
- Background: PubMed 16840747Erin EM, Leaker BR, Nicholson GC, Tan AJ, Green LM, Neighbour H, Zacharasiewicz AS, Turner J, Barnathan ES, Kon OM, Barnes PJ, Hansel TT. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med. 2006 Oct 1;174(7):753-62. doi: 10.1164/rccm.200601-072OC. Epub 2006 Jul 13.
- Results publication: PubMed 28625806Kaler M, Barochia AV, Weir NA, Cuento RA, Stylianou M, Roth MJ, Filie AC, Vaughey EC, Nathan SD, Levine SJ. A randomized, placebo-controlled, double-blinded, crossover trial of pioglitazone for severe asthma. J Allergy Clin Immunol. 2017 Dec;140(6):1716-1718. doi: 10.1016/j.jaci.2017.05.033. Epub 2017 Jun 15.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The NIH Biomedical Translational Research Information System
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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.
Stewart J Levine, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
2 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 Pioglitazone in people with Severe, Refractory Asthma and Airway Inflammation, run by National Heart, Lung, and Blood Institute (NHLBI) 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 35 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 Sep 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.
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 5 Sep 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?
16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00994175, which also lists 4 linked publications.
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 Sep 2017.