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

NCT00994175 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 09024409-H-0244
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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.

Conditions

Severe, Refractory Asthma; Airway Inflammation; Airflow Obstruction

Keywords

Pioglitazone; Severe, Refractory Asthma; Peroxisome Proliferator-Activated Receptor Gamma; Airflow Obstruction; Airway Inflammation; Asthma

Outcome Measures

Primary Outcomes (2)

• 16 Weeks - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score

  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

  16 weeks

• Baseline - Juniper Asthma Quality of Life Questionnaire (AQLQ) Score

  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

Study Arms (2)

Pioglitazone, Then Placebo

EXPERIMENTAL

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

Placebo, Then Pioglitazone

EXPERIMENTAL

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

Interventions

Pioglitazone DRUG

Pioglitazone, Then Placebo; Placebo, Then Pioglitazone

Placebo DRUG

Pioglitazone, Then Placebo; Placebo, Then Pioglitazone

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:

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

INOVA Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Related Publications (4)

• 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

• Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE, Green RH, Bradding P, Brightling CE, Wardlaw AJ, Pavord ID. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006 Feb 16;354(7):697-708. doi: 10.1056/NEJMoa050580.

  PMID: 16481637 BACKGROUND

• Erin EM, Leaker BR, Nicholson GC, Tan AJ, Green LM, Neighbour H, Zacharasiewicz AS, Turner J, Barnathan ES, Kon OM, Barnes PJ, Hansel TT. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med. 2006 Oct 1;174(7):753-62. doi: 10.1164/rccm.200601-072OC. Epub 2006 Jul 13.

  PMID: 16840747 BACKGROUND

• Kaler M, Barochia AV, Weir NA, Cuento RA, Stylianou M, Roth MJ, Filie AC, Vaughey EC, Nathan SD, Levine SJ. A randomized, placebo-controlled, double-blinded, crossover trial of pioglitazone for severe asthma. J Allergy Clin Immunol. 2017 Dec;140(6):1716-1718. doi: 10.1016/j.jaci.2017.05.033. Epub 2017 Jun 15.

  PMID: 28625806 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

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

Results Point of Contact

• Title: Levine, Stewart
• Organization: National Heart Lung and Blood Institute

levines@nhlbi.nih.gov

+1 301 402 1448

Study Officials

• Stewart J Levine, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2009
• First Posted: October 14, 2009
• Study Start: September 23, 2009
• Primary Completion: June 24, 2016
• Study Completion: June 24, 2016
• Last Updated: September 5, 2017
• Results First Posted: September 5, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (2)