A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma
Condition: Severe, Refractory Asthma; Airway Inflammation; Airflow Obstruction
MeSH terms: Asthma; Inflammation
Study type: Interventional
Phase: Phase 2

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 ), 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.
    

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.
    

Intervention name(s): Pioglitazone; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Pioglitazone; Severe, Refractory Asthma; Peroxisome Proliferator-Activated Receptor Gamma; Airflow Obstruction; Airway Inflammation; Asthma