A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00994175

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:

MedlinePlus related topics: Asthma

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

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:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

Detailed Description:

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.
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	kalerm@nhlbi.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

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Stewart J Levine, M.D.

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

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. Review. No abstract available.

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.

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. Epub 2006 Jul 13.

Responsible Party:	Stewart J. Levine, M.D./National Heart, Lung, and Blood Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00994175 History of Changes
Other Study ID Numbers:	090244, 09-H-0244
Study First Received:	October 10, 2009
Last Updated:	April 13, 2012
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, 2012