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

Phase 2

Completed

• Conditions: Airway Inflammation; Severe, Refractory Asthma; Airflow Obstruction
• Interventions: Drug: Pioglitazone; Drug: Placebo

• Registration Number: NCT00994175
• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief 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.

Study Timeline

• Study Start: 2009-09-23
• Study First Submitted: 2009-10-10
• Study First Submitted QC: 2009-10-10
• Study First Posted: 2009-10-14
• Primary Completion: 2016-06-24
• Study Completion: 2016-06-24
• Results First Submitted: 2017-06-16
• Status Verified: 2017-08
• Results First Submitted QC: 2017-08-01
• Last Update Submitted: 2017-08-01
• Results First Posted: 2017-09-05
• Last Update Posted: 2017-09-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Pioglitazone, Then Placebo	Pioglitazone	Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the first treatment phase, followed by 45 mg daily for an additional 14 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the placebo phase for 16 weeks in the second treatment phase to receive the placebo.
Pioglitazone, Then Placebo	Placebo	Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the first treatment phase, followed by 45 mg daily for an additional 14 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the placebo phase for 16 weeks in the second treatment phase to receive the placebo.
Placebo, Then Pioglitazone	Pioglitazone	Placebo was administered for 16 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the Pioglitazone treatment group. Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the treatment phase, followed by 45 mg daily for an additional 14 weeks.
Placebo, Then Pioglitazone	Placebo	Placebo was administered for 16 weeks. This was followed by a 4-week washout period. Subjects were assessed for clinical stability during a second 4-week run-in period prior to crossing over to the Pioglitazone treatment group. Pioglitazone, 30 mg daily, was administered for the initial 2 weeks of the treatment phase, followed by 45 mg daily for an additional 14 weeks.

Primary Outcome Measures

Name	Time	Method
16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score	16 weeks	Juniper Asthma Quality of Life Questionnaire (AQLQ) score at the end of the pioglitazone treatment period as compared to the placebo treatment period. The AQLQ is scored on a 7-point scale with 7 = not impaired at all, 1 = severly impaired
Baseline - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score	Baseline	Juniper Asthma Quality of Life Questionnaire (AQLQ) score at the end of the pioglitazone treatment period as compared to the placebo treatment period. The AQLQ is scored on a 7-point scale with 7 = not impaired at all, 1 = severly impaired

Trial Locations

Locations (2)

INOVA Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States