Genetic Susceptibility to Ozone in Mild Asthmatic Volunteers

NCT00287365 | Completed Results

• 2 other identifiers: GCRC-2371NCCAM 1PO1AT002620
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Asthma

Outcome Measures

Primary Outcomes (1)

• Post Ozone Change in Lung Function (FEV1) Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects

  6 hours post exposure

Secondary Outcomes (2)

• Secondary Endpoints Include Post Ozone Airway PMN Influx Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects

  6 hours post exposure

• % Decrease in FVC in Asthmatics Between Subjects With GSTM1 Null Genotype Compared to GSTM1 Sufficient Subjects

  6 hours post exposure

Study Arms (1)

1-ozone

EXPERIMENTAL

Mildly asthmatic subjects with GSTM1 null genotype compared to GSTM1 sufficient subjects

Drug: ozone

Interventions

ozone DRUG

2 hour exposure to 0.4 ppm ozone

Also known as: O3

1-ozone

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Environmental Protection Agency (EPA): collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• UNC Center for Environmental Medicine, Asthma and Lung Biology

MeSH Terms

Interventions

Ozone

Intervention Hierarchy (Ancestors)

Oxygen; Gases; Inorganic Chemicals

Results Point of Contact

• Title: David B. Peden, MD, MS
• Organization: University of North Carolina at Chapel Hill

dpeden@med.unc.edu

919-966-0768

Study Officials

• David B. Peden, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2006
• First Posted: February 6, 2006
• Study Start: January 1, 2006
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: October 13, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)