Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics

Condition(s) targeted: Asthma

Intervention: pioglitazone (Drug); placebo (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: University of Pittsburgh

Official(s) and/or principal investigator(s):
Fernando Holguin, MD, MPH, Principal Investigator, Affiliation: University of Pittsburgh

Overall contact:
Fernando L. Holguin, MD, MPH, Phone: 412-692-2210, Email: holguinf@upmc.edu

Asthmatics who are significantly overweight tend to have more severe symptoms, more flare ups, and are more likely to have poorly-controlled asthma when compared to other asthmatics.

Researchers believe this occurs because excess adipose tissue (fat) in the body can cause higher-than-normal levels of leptin and lower-than-normal levels of adiponectin in the blood.

The researchers of this study are testing a medication called pioglitazone in overweight asthmatics because they believe it can help regulate leptin and adiponectin and that this may improve symptoms of asthma.

Official title: A Randomized, Placebo-Controlled Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Airway reactivity will be measured with methacholine challenge testing following ATS guidelines

Secondary outcome:

Pulmonary function as measured by FEV1 and FVC following ATS guidelines

Asthma symptoms and control will be objectively monitored using the Juniper Questionnaire, Asthma Quality of Life Questionnaire, and St. George Respiratory Questionnaire

Detailed description: Participants in this study will be randomly assigned (like the flip of a coin) to pioglitazone or a placebo (an inactive pill). They will be given study medication to take everyday for 12 weeks (3 months).

Participants will complete a number of asthma-related questionnaires and a variety of pulmonary function tests. Participants will undergo physical exams, an electrocardiogram, and blood sampling to measure leptin, adiponectin, markers of inflammation, blood cell counts, glucose levels, BNP hormone levels, and liver function.

To monitor participants throughout the study, follow-up visits will be done at 2, 6, and 12 weeks after starting study drug. At these visits many of the pulmonary function tests and questionnaires will be repeated.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Asthma diagnosed by a physician at least 1 year prior to study enrollment

- Poorly-controlled asthma at study enrollment

- Non smokers (stopped smoking at least 1 year ago) and limited life-time history of

smoking

- Body mass index 30-60

- Responds to methacholine challenge test with PC20 of <16 mg/ml

- On a stable dose of inhaled corticosteroid for at least 4 weeks prior to study entry

- FEV1 >60% predicted

- Able to obtain weekly weights at home

Exclusion Criteria:

- Oral steroids within the past 4 weeks

- Lung pathology other than asthma

- Other significant non-pulmonary co-morbidities such as: coronary artery disease,

peripheral vascular disease, cerebrovascular disease, congestive heart failure with an ejection fraction <50%, liver disease or elevated liver enzymes at baseline, malignancy (excluding non-melanoma skin cancers), AIDS, renal failure with serum creatinine >3. 0, or disorders requiring steroid treatment such as vasculitis, lupus, rheumatoid arthritis

- B-type natriuretic peptide (BNP) >400 pg/mL

- Pregnant or lactating

- Currently taking a beta blocker, a CYP2C8 inhibitor or inducer such as gemfibrozil or

rifampin, a TZD (thiazolidinedione), or allergic to TZD

- Taking antioxidants, including multivitamins (if taking a multivitamin, a 4-week

washout period is required prior to enrollment)

- Illicit drug use within the past year

- Current/active upper respiratory infection (if active URI, wait until asymptomatic

for 1 week to enroll)

- Asthma exacerbation within the past 4 weeks (includes ER, urgent care, or hospital

visits due to asthma resulting in an increase in asthma-related medications)

- Undergoing evaluation for sleep apnea, or plans to institute treatment for sleep

apnea (patients on a stable treatment regimen for sleep apnea for the last 3 months will be allowed to participate)

- Clinically significant abnormalities present on screening 12-lead electrocardiogram

- Women of childbearing potential using oral contraceptives who are not willing to use

a second method of contraception during the study

Fernando L. Holguin, MD, MPH, Phone: 412-692-2210, Email: holguinf@upmc.edu

University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Asthma informational website

Asthma informational website

Related publications:

Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002 Feb;25(2):401. No abstract available.

Lee KS, Kim SR, Park SJ, Park HS, Min KH, Jin SM, Lee MK, Kim UH, Lee YC. Peroxisome proliferator activated receptor-gamma modulates reactive oxygen species generation and activation of nuclear factor-kappaB and hypoxia-inducible factor 1alpha in allergic airway disease of mice. J Allergy Clin Immunol. 2006 Jul;118(1):120-7. Epub 2006 May 19.

Starting date: January 2009
Ending date: March 2011
Last updated: October 16, 2008