Association Between Increased Oxidative Stress, Anti-Inflammatory Fatty Acid Formation, and Airway Infection in People With Asthma and Chronic Obstructive Pulmonary Disease

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00595114
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 43
• Location: 1
• Duration (Months): 20
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

Chronic obstructive pulmonary disease (COPD) and asthma are common respiratory diseases in which people experience long-term inflammation of the lungs. Exacerbations, or prolonged worsening of symptoms, of asthma and COPD are often life-threatening and can lead to frequent need for hospitalization. Even with the proper use of bronchodilators, corticosteroids, and other currently available medications, clinical responses among people with COPD and asthma are variable. There remains a significant unmet clinical need for new therapeutic approaches and insights, including the identification of biomarkers to accurately assess the presence of airway infection and intensity of airway inflammation. This study will investigate potential natural biological causes and new biomarkers for increased susceptibility to persistent airway infection in asthma and COPD.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Pulmonary Disease, Chronic Obstructive

Detailed Description

COPD and asthma are chronic lung diseases that result in impaired air flow in the lungs, often causing coughing, wheezing, and shortness of breath. In uncontrolled COPD and asthma, people may experience a rapid worsening of symptoms, which may include fever, difficulty breathing, and chest pain. These exacerbations are the most serious expression of asthma and COPD and are usually caused by lung infections or air allergens. However, the biological basis for susceptibility to airway infection and inflammation is not well understood. Increased oxidative stress within the airways has been linked to several airway diseases. This increase in oxidative stress may reduce production of key fatty acid anti-inflammatory mediators. In turn, this may disrupt the airway's natural immune response mechanisms, making the airways more vulnerable to infection or inflammation during COPD and asthma exacerbations. This ancillary study will determine whether susceptibility to persistent airway infection in asthma and COPD stems from increased oxidative stress that impairs the natural formation of protective fatty acid mediators.

This ancillary study will use data biological samples, including blood and sputum, from participants currently enrolled in the Macrolides in Asthma (MIA; NCT00318708) and the Antileukotriene Therapy for COPD Exacerbations (KIA; NCT01097694). Biological samples will undergo fatty acid mediator analysis and RNA isolation. There will be no study visits for this study.

Study Design

• Study Type: Observational
• Actual Enrollment: 43 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Ancillary Study of Oxidative Stress and Anti-Inflammatory Lipids in Airway Disease in the MIA (ACRN) and LEUKO (CCRN) Trials
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
MIA 1 Participants from the MIA trial who are polymerase chain reaction (PCR) negative and have received treatment with placebo
MIA 2 Participants from the MIA trial who are PCR negative and have received treatment with the antibiotic clarithromycin
MIA 3 Participants from the MIA trial who are PCR positive and have received treatment with placebo
MIA 4 Participants from the MIA trial who are PCR positive and have received treatment with the antibiotic clarithromycin
LEUKO 1 Participants from the LEUKO trial who have received treatment with placebo
LEUKO 2 Participants from the LEUKO trial who have received treatment with zileuton

Outcome Measures

Primary Outcome Measures

1. 8-isoprostane Levels as Biochemical Markers for Nonenzymatic Oxidative Stress in Asthma [Measured at completion of sample analysis]

   8-isoprostane levels in sputum

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• No change from the MIA and LEUKO trials

Exclusion Criteria:

• No change from the MIA and LEUKO trials

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Bruce D. Levy, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bruce D. Levy, Principal Investigator, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00595114
• Other Study ID Numbers: 1421; R01HL090927; HL090927
• First Posted: Jan 16, 2008
• Last Update Posted: Oct 19, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Bruce D. Levy, Principal Investigator, Brigham and Women's Hospital: COPD; Airway; Inflammation; Infection; Lipid Mediators; Oxidative Stress
• Additional relevant MeSH terms: Asthma; Lung Diseases; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Arm/Group Title	MIA 1	KIA 1
Arm/Group Description	Participants from the MIA trial with mild asthma	Participants from the KIA trial with severe asthma
Period Title: Overall Study
STARTED	24	19
COMPLETED	24	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	MIA 1	KIA 1	Total
Arm/Group Description	Participants from the MIA trial with mild asthma	Participants from the KIA trial with severe asthma	Total of all reporting groups
Overall Participants	24	19	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37 (10)	40 (11)	38 (10)
Sex: Female, Male (Count of Participants)
Female	17 70.8%	9 47.4%	26 60.5%
Male	7 29.2%	10 52.6%	17 39.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 20.8%	3 15.8%	8 18.6%
Not Hispanic or Latino	19 79.2%	16 84.2%	35 81.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
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	15 62.5%	8 42.1%	23 53.5%
White	9 37.5%	11 57.9%	20 46.5%
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	24 100%	19 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	8-isoprostane Levels as Biochemical Markers for Nonenzymatic Oxidative Stress in Asthma
Description	8-isoprostane levels in sputum
Time Frame	Measured at completion of sample analysis

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MIA 1	KIA 1
Arm/Group Description	Participants from the MIA trial with mild asthma	Participants from the KIA trial with severe asthma
Measure Participants	24	19
Mean (Standard Deviation) [pg/ml]	292.4 (51.0)	421.8 (195.4)

Adverse Events

Arm/Group Title	MIA 1		KIA 1
Arm/Group Description	Participants from the MIA trial with mild asthma		Participants from the KIA trial with severe asthma
All Cause Mortality
	MIA 1		KIA 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MIA 1		KIA 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	MIA 1		KIA 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

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.