GLITZ: Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics (Glitz Asthma)

• Sponsor: University of Vermont (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00787644
• Collaborator: American Lung Association (Other), University of Pittsburgh (Other)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 59
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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 bosy can cause higher-than-normal levels of leptin and lower 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.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Obesity	Drug: Pioglitazone; Drug: Placebo	Phase 2

Detailed Description

Participants in this study will be randomly assigned (like the flip of a coin) to pioglitazone or placebo (an inactive pill). They will be given study medication to take every day 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics. (The GLITZ Asthma Study)
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: Pioglitazone; Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months)
Placebo Comparator: 2	Drug: Placebo; Matching placebo (inert tablet)

Outcome Measures

Primary Outcome Measures

1. PC20 [12 weeks]

   Airway reactivity will be measured with methacholine challenge testing following ATS guidelines. This is the concentration of methacholine that produces a 20% decrease in lung function (measured by forced expiratory volume in 1 second)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 lifetime 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:

• Systemic 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) >400pg/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 (if taking a multivitamin must be on a stable regimen 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Vermont Lung Center at the University of Vermont	Colchester	Vermont	United States	05446

Sponsors and Collaborators

• University of Vermont
• American Lung Association
• University of Pittsburgh

Investigators

• Principal Investigator: Anne E Dixon, MD, The Vermont Lung Center at the University of Vermont

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Asthma informational website
• Asthma informational website

Publications

• Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002 Feb;25(2):401.
• 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.

• Responsible Party: Anne Dixon, M.D., University of Vermont
• ClinicalTrials.gov Identifier: NCT00787644
• Other Study ID Numbers: GLITZ Asthma
• First Posted: Nov 7, 2008
• Last Update Posted: Feb 26, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Anne Dixon, M.D., University of Vermont: Asthma; Adipose Tissue; Asthmatics; Pioglitazone; Actos; Obesity; Exacerbation; Fat; Overweight; Leptin; Adiponectin; Wheezing; Vermont; Pulmonary; Lung
• Additional relevant MeSH terms: Asthma; Pioglitazone

Study Results

Participant Flow

Pre-assignment Detail	5 participants did not qualify for randomization as they had a negative methacholine.

Arm/Group Title	1. Pioglitazone	2. Placebo
Arm/Group Description	Pioglitazone: Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months)	Placebo: Matching placebo (inert tablet)
Period Title: Overall Study
STARTED	12	11
COMPLETED	10	9
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	1. Pioglitazone	2. Placebo	Total
Arm/Group Description	Pioglitazone: Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months)	Placebo: Matching placebo (inert tablet)	Total of all reporting groups
Overall Participants	12	11	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	11 100%	23 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 58.3%	8 72.7%	15 65.2%
Male	5 41.7%	3 27.3%	8 34.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 33.3%	2 18.2%	6 26.1%
White	8 66.7%	9 81.8%	17 73.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	11 100%	23 100%
PC20 (mg/ml) [Median (Standard Deviation) ]
Median (Standard Deviation) [mg/ml]	1.60 (5.91)	1.99 (3.08)	1.90 (3.08)

Outcome Measures

1. Primary Outcome

Title	PC20
Description	Airway reactivity will be measured with methacholine challenge testing following ATS guidelines. This is the concentration of methacholine that produces a 20% decrease in lung function (measured by forced expiratory volume in 1 second)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1. Pioglitazone	2. Placebo
Arm/Group Description	Pioglitazone: Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months)	Placebo: Matching placebo (inert tablet)
Measure Participants	10	9
Median (Standard Deviation) [mg/ml]	5.08 (7.42)	2.37 (15.22)

Adverse Events

Arm/Group Title	1. Pioglitazone		2. Placebo
Arm/Group Description	Pioglitazone: Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months)		Placebo: Matching placebo (inert tablet)
All Cause Mortality
	1. Pioglitazone		2. Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1. Pioglitazone		2. Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	1. Pioglitazone		2. Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.