Protocol Number: 09-H-0244

Title:

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

Number:

09-H-0244

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(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.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

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.

- 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 > 10 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

- 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.

- History of 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.

Special Instructions:

Currently Not Provided

Keywords:

Pioglitazone

Severe, Refractory Asthma

Peroxisome Proliferator-Activated Receptor Gamma

Airflow Obstruction

Airway Inflammation

Recruitment Keyword(s):

Asthma

Condition(s):

Severe, Refractory Asthma

Airway Inflammation

Airflow Obstruction

Investigational Drug(s):

Pioglitazone Hydrochloride

Investigational Device(s):

None

Intervention(s):

Drug: Pioglitazone

Supporting Site:

National Heart, Lung, and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoidsÑnew mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23

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.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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