Genetic Susceptibility to Ozone in Mild Asthmatic Volunteers - Full Text View

Sponsor:	University of North Carolina, Chapel Hill
Collaborator:	Environmental Protection Agency (EPA)
Information provided by:	University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT00287365

Purpose

Recent reports have shown that people with asthma who have a particular gene, known as the GSTM1 null gene, are more susceptible to the effect of air pollutants. The purpose of this research study is to learn if volunteers who have asthma and have a GSTM1 null gene have increased response (change in lung function and increase in lung cells collected from sputum) compared to volunteers with asthma who have the GSTM1 sufficient gene when challenged with 0.4 ppm ozone during intermittent exercise. The principal purpose of this study is to identify hyper-responsive, responsive and non-responsive groups of human subjects with mild asthma based on their airway neutrophilic response to ozone exposure, and to perform analyses on DNA from airway cells to explore possible differences in genetic profiles between the three groups. An additional pilot aim is to compare expression of a small number of specific genes of interest in a subset of ozone-responsive and ozone-non-responsive subjects with mild asthma.

Condition	Intervention
Mild Asthma	Drug: ozone

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	Glutathione S Transferase M1 (GSTM1) Genotype Associated Susceptibility to Airway Response to Ozone in Mild Asthmatic Volunteers.

Resource links provided by NLM:

MedlinePlus related topics: Asthma Ozone

U.S. FDA Resources

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:

post ozone change in lung function (FEV1) between subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects [ Time Frame: 0-24 hours post exposure ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Secondary endpoints include post ozone airway PMN influx between subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects [ Time Frame: 0-24 hours post exposure ] [ Designated as safety issue: No ]
% decrease in FVC between subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects [ Time Frame: 0-24 hours post exposure ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	January 2006
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Mildly asthmatic subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects	Drug: ozone 2 hour exposure to 0.4 ppm ozone Other Name: O3

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Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

healthy volunteers with mild asthma
Normal lung function,
Oxygen saturation of > 94 %
Normal blood pressure

Exclusion Criteria:

A history of significant chronic illnesses
Allergy to any medications which may be used or prescribed in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose, polyethylene glycol)
Positive pregnancy test within 48 hours of the time of challenge
Subjects currently taking medications which may impact the results of the ozone challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics).
Mega doses of vitamins and supplements, homeopathic/naturopathic medicines
Any acute, non-chronic, medical conditions occurring in the prior two weeks. Such illnesses must be totally resolved symptomatically for 2 weeks and documentation of normal lung function must be obtained.
Unspecified illnesses, which in the judgment of the investigator might increase the risk associated with ozone inhalation challenge, will be a basis for exclusion.
Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
Use of systemic steroid therapy within the preceding 12 months.
> 0.5 pack year history of tobacco use
Use of inhaled steroids, cromolyn or leukotriene inhibitors initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy.
Use of daily theophylline within the past month.
Pregnancy or nursing a baby.
Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
Exacerbation of asthma more than 2x/week which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
Dosing level of an inhaled steroid must be consistent with mild episodic asthma as outlined by the NHLBI NAEPP guidelines. Use of inhaled steroid at doses typically used for moderate or severe asthma will result in exclusion of that individual from the protocol.
Students or staff members who work directly for the PI, Dr David Peden, are excluded from study participation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00287365

Contacts

Contact: Westat Recruitment

919-966-0604

Locations

United States, North Carolina
Center for Environmental Medicine, Asthma and Lung Biology	Recruiting
Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Environmental Protection Agency (EPA)

Investigators

Principal Investigator:

David B. Peden, MD

University of NC Center for Environmental Medicine, Asthma and Lung Biology

More Information

Additional Information:

UNC Center for Environmental Medicine, Asthma and Lung Biology This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David Peden, MD, Center for Environmental Medicine, University of North Carolina at Chapel Hill
ClinicalTrials.gov Identifier:	NCT00287365 History of Changes
Other Study ID Numbers:	GCRC-2371, NCCAM 1PO1AT002620
Study First Received:	February 3, 2006
Last Updated:	July 12, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board

Additional relevant MeSH terms:

Disease Susceptibility
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on February 09, 2012