Pioglitazone Hydrochloride (Actos(Registered Trademark)) to Treat Asthma

NCT00604578 | Withdrawn Phase 2

• 2 other identifiers: 08004708-H-0047
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This study will test whether pioglitazone hydrochloride (Actos (Registered Trademark) 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 a1 year and whose symptoms are not well controlled with high doses of inhaled corticosteroids with or without long-acting bronchodilators may be eligible for this study. Candidates are screened with breathing tests, an allergy skin test, chest x-ray, electrocardiogram (ECG), echocardiogram (ultrasound test of the heart), blood tests, and DEXA scan (an x-ray to measure bone thickness) to make sure they are eligible for the study. Then, participants undergo tests and procedures in the following study phases: Phase 1 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 have a sputum induction (sputum collection test). For this test, the participants inhale a salt-water mist and are asked to collect sputum into a plastic cup. 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 10 weeks. They return to the clinic after 2 weeks to repeat the tests done in Phase 1 and to monitor any reactions to the study drug or placebo. If there are no problems, the amount of medication is increased once, and then they return for follow-up evaluations every 2 weeks for 8 weeks. Pulmonary function tests, sputum collection and DEXA scan are repeated after 10 weeks on medication. Phase III Patients return for follow-up 1 month after stopping the medication or placebo to monitor their asthma. ...

Conditions

Asthma; Airway Inflammation; Airflow Obstruction; Airway Hyperactivity

Keywords

Pioglitazone; Asthma; Peroxisome Proliferator-Advanced Receptor Gamma; Airflow Obstruction; Airway Inflammation

Outcome Measures

Primary Outcomes (1)

• The change in post-bronchodilator FEV1.

  10 weeks

Secondary Outcomes (1)

• Airway inflammation, Airflow Obstruction, Airway Hyperreactivity, Asthma Symptoms, Rate of mild exacerbation, Rate of severe exacerbation, Asthma Quality-of-life, Blood Eosinophil Counts, Serum IgE and Exhaled Nitric Oxide Levels.

  10 weeks

Interventions

Pioglitazone Hydrochloride DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (great than or equal to 440 ucg/day) fluticasone inhaler or equivalent dose of another inhaled corticosteroid) with or without an inhaled long-acting beta-2-agonist) for at least 3 months.
• Patients must meet the EPR-3 criteria for not well controlled asthma. The EPR-3 definition for not well controlled asthma includes any of the following features in a week (unless otherwise indicated): daytime asthma symptoms great than 2 days/week, limitation of activities, nocturnal symptoms or awakening greater than 2 times/month, need for reliever/rescue treatment greater than 2 days/week, PEF or FEV(1) less than 80% predicted.
• Pre-bronchodilator FEV(1) greater than or equal to 55% of predicted and post-bronchodilator FEV(1) greater than or equal to 60% 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 and unchanged use of asthma maintenance therapy. Additional criteria for disease stability include the absence of hospitalization for asthma or the need for a course of oral corticosteroids during the preceding 3 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% 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.

You may not qualify if:

• 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 10 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 congestive heart failure.
• 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 times upper limit of normal.
• History of inflammatory bowel disease.
• History of cancer (other than dermatologic cancer).
• History of drug or alcohol abuse.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Fairfax Hospital

Falls Church, Virginia, 22046, United States

Location

Related Publications (3)

• Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006 Aug 26;368(9537):804-13. doi: 10.1016/S0140-6736(06)69290-8.

  PMID: 16935691 BACKGROUND

• 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.

  PMID: 16236742 BACKGROUND

• Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006 Jun 22;354(25):2689-95. doi: 10.1056/NEJMct055184. No abstract available.

  PMID: 16790701 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 8, 2008
• First Posted: January 30, 2008
• Study Start: January 4, 2008
• Primary Completion: October 30, 2009
• Study Completion: October 30, 2009
• Last Updated: July 2, 2017

Record last verified: 2009-10-30

Locations

US (2)