Back to resultsA Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
Primary Purpose
Severe, Refractory Asthma, Airway Inflammation, Airflow Obstruction
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Severe, Refractory Asthma focused on measuring Pioglitazone, Severe, Refractory Asthma, Peroxisome Proliferator-Activated Receptor Gamma, Airflow Obstruction, Airway Inflammation, Asthma
Eligibility Criteria
- INCLUSION CRITERIA:
- 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
EXCLUSION CRITERIA:
- 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.
- 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.
Sites / Locations
- National Institutes of Health Clinical Center, 9000 Rockville Pike
- INOVA Fairfax Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Pioglitazone, Then Placebo
Placebo, Then Pioglitazone
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Full Information
NCT ID
NCT00994175
First Posted
October 10, 2009
Last Updated
August 1, 2017
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00994175
Brief Title
A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
Official Title
A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
September 23, 2009 (undefined)
Primary Completion Date
June 24, 2016 (Actual)
Study Completion Date
June 24, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe, Refractory Asthma, Airway Inflammation, Airflow Obstruction
Keywords
Pioglitazone, Severe, Refractory Asthma, Peroxisome Proliferator-Activated Receptor Gamma, Airflow Obstruction, Airway Inflammation, Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone, Then Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo, Then Pioglitazone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score
Description
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
Time Frame
16 weeks
Title
Baseline - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score
Description
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
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
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
EXCLUSION CRITERIA:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stewart J Levine, M.D.
Organizational Affiliation
National Heart, Lung, and Blood Institute (NHLBI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
INOVA Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The NIH Biomedical Translational Research Information System
Citations:
PubMed Identifier
16236742
Citation
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.
Results Reference
background
PubMed Identifier
16481637
Citation
Berry 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.
Results Reference
background
PubMed Identifier
16840747
Citation
Erin 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 Reference
background
PubMed Identifier
28625806
Citation
Kaler 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.
Results Reference
result
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2009-H-0244.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
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