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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 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 13, 2014
Last verified: April 2014
  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 ), which is used to treat patients with diabetes, may be effective for treating severe asthma. Researchers are interested in determining whether Actos 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: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pioglitazone
    N/A
Detailed Description:

New therapies are needed for patients with asthma who are sub-optimally controlled by standard measures. Pioglitazone hydrochloride (Actos ) 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 )
    • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 13, 2014
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 August 20, 2014