We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00994175
First Posted: October 14, 2009
Last Update Posted: September 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
  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 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
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) ( National Heart, Lung, and Blood Institute (NHLBI) ):

Primary Outcome Measures:
  • 16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score [ Time Frame: 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 [ Time Frame: 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


Enrollment: 15
Study Start Date: September 23, 2009
Study Completion Date: June 24, 2016
Primary Completion Date: June 24, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone, Then 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.
Drug: Pioglitazone Drug: Placebo
Experimental: Placebo, Then 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.
Drug: Pioglitazone Drug: Placebo

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00994175


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Virginia
INOVA Fairfax Hospital
Falls Church, Virginia, United States, 22042
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Stewart J Levine, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00994175     History of Changes
Other Study ID Numbers: 090244
09-H-0244 ( Other Identifier: The National Institutes of Health )
First Submitted: October 10, 2009
First Posted: October 14, 2009
Results First Submitted: June 16, 2017
Results First Posted: September 4, 2017
Last Update Posted: September 4, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The NIH Biomedical Translational Research Information System

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
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