Protocol Number: 08-H-0047

Title:

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

Number:

08-H-0047

Summary:

This study will test whether pioglitazone hydrochloride (Actos® (Registered Trademark)) is effective for treating patients with asthma who do not respond to standard therapy. Experiments have shown that this drug, which is used to treat patients with diabetes, may be effective for treating asthma.

People between 18 and 75 years of age who have had asthma for at least 1 year and whose symptoms are not well controlled with medium to high doses of inhaled corticosteroids plus long-acting bronchodilators may be eligible for this study. Candidates are screened with blood and urine tests, breathing tests, an allergy skin test, chest x-ray, electrocardiogram (ECG) and echocardiogram (ultrasound test of the heart).

Participants undergo tests and procedures in two study phases, as follows:

Phase I

Participants are given a device to measure and record their lung function and asthma symptoms at home each morning and night for 4 weeks before starting the study medication. Lung function is also measured at clinic visits before and after inhaling a bronchodilator medicine. Before starting the study medication, participants are admitted to the hospital for fiberoptic bronchoscopy and lavage (rinse). For this test, plastic tube is placed in a vein to give medications. The mouth, throat and nose are numbed with lidocaine and the bronchoscope (a thin flexible tube) is placed through the nose or mouth into the lung airways to examine them. A salt water solution is infused through the tube and then removed by gentle suctioning from three areas of the lung (lavage). A soft brush is rubbed against the cells lining the lungs and then the tube is removed. The procedure takes about 20 to 30 minutes.

Phase II

Participants are randomly selected to receive either pioglitazone hydrochloride or placebo (a look-alike pill with no active ingredient) once a day for 18 weeks. They return to the clinic after 2 weeks to repeat the tests done in phase I and to monitor any reactions to the study drug or placebo. If there are no problems, the amount of medication is increased and they return for follow-up evaluations every 2 weeks for 6 weeks, then monthly for 3 months. Pulmonary function tests and bronchoscopy and lavage are repeated after 18 weeks on medication.

Phase III

Patients return for follow-up 1 month after stopping the medication or placebo to monitor their asthma.

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:

-Patients will be between 18 and 75 years of age, male or female, with a diagnosis of asthma for at least one year.

-Patients must have reversible airflow obstruction as defined by a positive methacholine bronchoprovocation challenge or a positive response to inhaled bronchodilators.

-Patients must be treated with EPR-3 Step 5 therapy (high dose greater than 440 microcg/day) fluticasone inhaler or equivalent dose of another inhaled corticosteroid) plus an inhaled long-acting beta 2-agonist) for at least 3 months.

-Patients must meet the EPR-3 criteria for not well controlled asthma (1, 2). The EPR-3 definition for not well controlled asthma includes any of the following features in a week (unless otherwise indicated): daytime asthma symptoms greater than 2 days/week, limitation of activities, nocturnal symptoms or awakening greater than two times/month, need for reliever/rescue treatment greater than 2 days/week, PEF or FEV(1) less than 80 percent predicted.

-FEV1 greater than 60 percent of predicted.

-During the 6 weeks prior to enrollment, patients should have stable asthma as defined by the absence of unscheduled health care visits for asthma care, unchanged use of asthma maintenance therapy, and stable use of rescue medication (4 puffs or fewer of a short-acting bronchodilator, such as albuterol delivered by metered dose inhaler) during 24 hours for symptom relief on two consecutive days. Additional criteria for disease stability include the absence of hospitalization for asthma or the need for a course of oral corticosteroids during the preceding 6 months.

-Research subjects must have a positive skin test to a common aeroallergen, such as dust mite, cat, short ragweed, cockroach, or grass or a prior history of severe allergy or anaphylaxis.

-Chest radiograph without evidence of pulmonary disease, other than asthma.

-Left ventricular ejection fraction greater than or equal to 50 percent. by echocardiogram.

-For women of childbearing potential, negative pregnancy test within 2 weeks prior to study and willingness to adhere to reliable birth control methods during the study.

-Subjects with a history of dermatologic cancers may be included if they have been cancer-free for at least 5 years prior to enrollment.

EXCLUSION CRITERIA:

-A known history of hypersensitivity to pioglitazone.

-Maintenance asthma therapy with oral corticosteroids, xolair (anti-IgE), methotrexate, cytoxan, gold salts, or cyclosporine.

-Cigarette smoking within the past 3 months or a prior history of greater than 5 cumulative pack-years.

-Viral or bacterial upper respiratory tract infection within 6 weeks prior to the screening visit.

-Investigational therapy for any indication within 1 month prior to the screening visit.

-History of lung disease other than asthma (i.e., COPD, sarcoidosis).

-History of diabetes mellitus, insulin secreting tumor, or symptomatic hypoglycemia.

-HIV or other known immunodeficiency.

-History of heart disease, congestive heart failure, previously diagnosed mitral valve prolapse, or bacterial endocarditis.

-Preexisting edema (2-plus or greater).

-Hemoglobin less than 12 gm/dl for males and less than 11 gm/dl for females.

-History of liver disease or abnormal liver function tests greater than 2 X upper limit of normal.

-History of inflammatory bowel disease.

-History of cancer (other than dermatologic cancer) or colon polyps.

-History of drug or alcohol abuse.

-Use of the following medications, which can interact with pioglitazone:

1. Gemfibrizol (Lopid)

2. Atazanivir (Reyataz)

3. Ritonavir (Norvir)

4. Rifampin (Rifampicin)

5. Carbamzepine (Tegretol)

6. Phenobarbital (Luminal)

7. Phenytoin (Dilantin)

8. Rifapentine (Priftin)

9. Secobarbital (Seconal)

10. Amiodarone (Cordarone, Pacerone)

11. Palitaxel (Taxol)

12. Replaglinide (Prandine)

13. Ketoconazole (Nizoral)

14. Atorvastatin (Lipitor® (Registered Trademark))

15. Nifedipine ER (Adalat CC)

-Allergy to lidocaine.

-Anti-coagulant medications.

-Any condition that, in the investigator's opinion, places the patient at undue risk for complications from pioglitazone therapy.

-Dexa bone scan (Tscore below -1 SD)

Special Instructions:

Currently Not Provided

Keywords:

Pioglitazone

Asthma

Peroxisome Proliferator-Advanced Receptor Gamma

Airflow Obstruction

Airway Inflammation

Recruitment Keyword(s):

Asthma

Condition(s):

Asthma

Airway Inflammation

Airflow Obstruction

Airway Hyperactivity

Investigational Drug(s):

Pioglitazone Hydrochloride

Investigational Device(s):

None

Intervention(s):

Drug: Pioglitazone Hydrochloride

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):

Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006 Aug 26;368(9537):804-13.

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

Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006 Jun 22;354(25):2689-95.

• 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 Networks and Applications, CC.

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