A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
This study is currently recruiting participants.
Verified June 2012 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
ClinicalTrials.gov Identifier:
NCT00994175
First received: October 10, 2009
Last updated: May 1, 2013
Last verified: June 2012
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Purpose
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(Registered Trademark)), which is used to treat patients with diabetes, may be effective for treating severe asthma. Researchers are interested in determining whether Actos(Registered Trademark) 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Severe, Refractory Asthma Airway Inflammation Airflow Obstruction |
Drug: Pioglitazone |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double-Blind Primary Purpose: Treatment |
| Official Title: | A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma |
Resource links provided by NLM:
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- Quality of life as determined by the validated Asthma Quality of Life Questionnaire (AQLQ) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Airway inflammation, airflow obstruction, asthma symptoms, asthma exacerbations, blood eosinophil counts, serum IgE and exhaled nitric oxide levels [ Time Frame: 3 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 300 |
| Study Start Date: | September 2009 |
| Estimated Study Completion Date: | December 2016 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: Pioglitazone
N/A
New therapies are needed for patients with asthma who are sub-optimally controlled by standard measures. Pioglitazone hydrochloride (Actos(Registered Trademark)) 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.
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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(Registered Trademark))
- 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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00994175
Contacts
| Contact: Maryann M Kaler, C.R.N.P. | (301) 451-5916 | mk371e@nih.gov |
| Contact: Stewart J Levine, M.D. | (301) 402-1553 | levines@nhlbi.nih.gov |
Locations
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 prpl@mail.cc.nih.gov | |
| United States, Virginia | |
| INOVA Fairfax Hospital | Recruiting |
| Falls Church, Virginia, United States, 22042 | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Stewart J Levine, M.D. | National Heart, Lung, and Blood Institute (NHLBI) |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ) |
| ClinicalTrials.gov Identifier: | NCT00994175 History of Changes |
| Other Study ID Numbers: | 090244, 09-H-0244 |
| Study First Received: | October 10, 2009 |
| Last Updated: | May 1, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
Pioglitazone Severe, Refractory Asthma Peroxisome Proliferator-Activated Receptor Gamma |
Airflow Obstruction Airway Inflammation Asthma |
Additional relevant MeSH terms:
|
Asthma Inflammation Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate |
Hypersensitivity Immune System Diseases Pathologic Processes Pioglitazone Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 23, 2013