Role of TLR4 in Environmental Asthma

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The overall goal of this project is to identify genes that are involved in the development of airflow obstruction and airway inflammation in asthmatics, and to determine whether polymorphisms in these differentially expressed genes predispose individuals to develop asthma. In this project, we hypothesize that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma.

Condition or disease	Intervention/treatment	Phase
Asthma	Biological: Lipopolysaccharide endotoxin	Phase 1

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	855 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Role of TLR4 in Environmental Asthma
Study Start Date :	September 2001
Actual Primary Completion Date :	August 2006
Actual Study Completion Date :	April 2008

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Challenge; Experimental Challenge Challenge 1 saline 5000EU 10,000EU 20,000EU Challenge 2 Saline 40,000EU 80,000EU

Biological: Lipopolysaccharide endotoxin; Delivered in nebulized form expressed in activity units(endotoxin units -EU). Subjects receive each dose 30 min after completing the previous dose, dose duration is approximately 10 minutes: Challenge One first saline then 5000 EU 10,000 EU 20,000 EU Challenge 1 and 2 must be at least 2 weeks apart. Challenge 2 Saline 40,000 EU 80,000 EU; Other Name: (CCRE)LPS endotoxin from E. Coli 0:113 maintained by NIH

Outcome Measures

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Primary Outcome Measures :

1. Ascertain individuals homozygous, and heterozygous for mutant TLR4 genotype, along with wild types by recruitment of healthy screening subjects in the community. [ Time Frame: completed ]

Secondary Outcome Measures :

1. Assess the effect of TLR4 genotype on LPS endotoxin induced immune responses and assess the association of the LPS-induced immune response with LPS-induced airway responses. [ Time Frame: 24 hours ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 40 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• vital signs within normal limits
• negative methacholine challenge (non asthmatic)
• normal PFT's, CXR, EKG
• negative allergy skin tests (non atopic)
• never cigarette smoker
• no chronic illness
• no daily meds except contraceptives
• able and willing to sign informed consent
• not an employee working for,or a student under the authority of the PI's

Exclusion Criteria:

• allergic rhinitis past or present
• chronic illness resulting in altered lung function
• chronic daily medications
• cigarette smoking
• allergy to acetaminophen or albuterol
• pregnant or nursing females
• PFT results below cut off
• Positive allergy skin test
• Abnormal CXR or EKG
• Positive methacholine challenge
• Infection in the previous 2 weeks
• Past or present allergen immunotherapy
• Occupational exposure to hay or grain
• Other medical or psychological conditions which, in the opinion of the PI, may create undue risk to the subject or interfere with the subject's ability to comply with protocol requirements.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

John Sundy

Investigators

Principal Investigator:	John S Sundy, M.D., PhD.	Duke University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	John Sundy, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT00671892 History of Changes
Other Study ID Numbers:	3030-07-8R5; 12496-CP-007 ( Other Identifier: NIEHS )
First Posted:	May 5, 2008
Last Update Posted:	July 16, 2013
Last Verified:	July 2013

Keywords provided by John Sundy, Duke University Medical Center:

LPS endotoxin; asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases	Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases