Diesel Exhaust and Mechanism of Asthma

NCT ID: NCT01699204

Last Updated: 2017-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-09-30

Study Completion Date

2011-10-31

Brief Summary

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This experiment is designed to test the hypothesis that oxidative stress is responsible for changes in airway responsiveness in humans exposed to diesel exhaust.

Detailed Description

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The specific aim is to test the hypothesis that diesel exhaust (DE) increases airway reactivity via oxidative stress, particularly in asthmatics. To test this hypothesis, we use a crossover in vivo experimental model in mild asthmatics and normal controls using a state-of-the-art diesel exhaust exposure facility.

Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for six days. On the final morning of supplementation, participants were exposed for 2 hours to either filtered air or diesel exhaust (300 µg·m-3 of particulate matter smaller than 2.5 microns). Twenty-six non-smokers between 19-49 years were studied under three experimental conditions (filtered air with placebo, diesel exhaust with placebo and diesel exhaust with N-acetylcysteine) using randomized, double-blind, crossover design, with a two week minimum washout between conditions. Methacholine challenge was performed pre-exposure (to determine baseline airway responsiveness) and post-exposure (to determine the effect of exposure).

Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Filtered air with placebo

Exposure for 2 hours to filtered air and placebo tablets 3 times daily for 6 days

Group Type PLACEBO_COMPARATOR

Filtered air

Intervention Type OTHER

A placebo tablet taken 3 times daily for 6 days prior to exposure to filtered air for 2 hours. The last supplement was taken the morning of the exposure

Diesel exhaust with placebo

Exposure for 2 hours to diesel exhaust and placebo tablets 3 times daily for 6 days

Group Type ACTIVE_COMPARATOR

Diesel exhaust

Intervention Type OTHER

A placebo tablet taken 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

Diesel exhaust with N-acetylcysteine

Exposure for 2 hours to diesel exhaust and N-acetylcysteine tablets (600 mg) 3 times daily for 6 days

Group Type EXPERIMENTAL

N-acetylcysteine

Intervention Type DIETARY_SUPPLEMENT

N-acetylcysteine 600mg taken orally 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

Diesel exhaust

Intervention Type OTHER

A placebo tablet taken 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

Interventions

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N-acetylcysteine

N-acetylcysteine 600mg taken orally 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

Intervention Type DIETARY_SUPPLEMENT

Diesel exhaust

A placebo tablet taken 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

Intervention Type OTHER

Filtered air

A placebo tablet taken 3 times daily for 6 days prior to exposure to filtered air for 2 hours. The last supplement was taken the morning of the exposure

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Between 19-49 years, non smokers, asthmatics, healthy controls

Exclusion Criteria

* Smokers, pregnant or co-existing medical condition for which diesel exhaust would confer significant risk (i.e. coronary artery disease)
Minimum Eligible Age

19 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Christopher Carlsten

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher Carlsten, MD MPH

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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University of British Columbia

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

References

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Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S. doi: 10.1378/chest.130.1_suppl.4S.

Reference Type BACKGROUND
PMID: 16840363 (View on PubMed)

Atkinson RW, Anderson HR, Sunyer J, Ayres J, Baccini M, Vonk JM, Boumghar A, Forastiere F, Forsberg B, Touloumi G, Schwartz J, Katsouyanni K. Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1860-6. doi: 10.1164/ajrccm.164.10.2010138.

Reference Type BACKGROUND
PMID: 11734437 (View on PubMed)

Janssen NA, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fischer P. The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren. Environ Health Perspect. 2003 Sep;111(12):1512-8. doi: 10.1289/ehp.6243.

Reference Type BACKGROUND
PMID: 12948892 (View on PubMed)

Mudway IS, Stenfors N, Duggan ST, Roxborough H, Zielinski H, Marklund SL, Blomberg A, Frew AJ, Sandstrom T, Kelly FJ. An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants. Arch Biochem Biophys. 2004 Mar 1;423(1):200-12. doi: 10.1016/j.abb.2003.12.018.

Reference Type BACKGROUND
PMID: 14871482 (View on PubMed)

Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.

Reference Type BACKGROUND
PMID: 8943829 (View on PubMed)

Stenfors N, Nordenhall C, Salvi SS, Mudway I, Soderberg M, Blomberg A, Helleday R, Levin JO, Holgate ST, Kelly FJ, Frew AJ, Sandstrom T. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Eur Respir J. 2004 Jan;23(1):82-6. doi: 10.1183/09031936.03.00004603.

Reference Type BACKGROUND
PMID: 14738236 (View on PubMed)

Hashimoto S, Gon Y, Takeshita I, Matsumoto K, Jibiki I, Takizawa H, Kudoh S, Horie T. Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. Am J Respir Crit Care Med. 2000 Jan;161(1):280-5. doi: 10.1164/ajrccm.161.1.9904110.

Reference Type BACKGROUND
PMID: 10619832 (View on PubMed)

McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, Harrington R, Svartengren M, Han IK, Ohman-Strickland P, Chung KF, Zhang J. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007 Dec 6;357(23):2348-58. doi: 10.1056/NEJMoa071535.

Reference Type BACKGROUND
PMID: 18057337 (View on PubMed)

Other Identifiers

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H08-02288

Identifier Type: -

Identifier Source: org_study_id