Role of TLR4 in Environmental Asthma

NCT00671892 | Completed Phase 1

• 2 other identifiers: 3030-07-8R512496-CP-007
• Study Type: interventional
• Target: 855
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

LPS endotoxin; asthma

Outcome Measures

Primary Outcomes (1)

• Ascertain individuals homozygous, and heterozygous for mutant TLR4 genotype, along with wild types by recruitment of healthy screening subjects in the community.

  completed

Secondary Outcomes (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.

  24 hours

Study Arms (1)

Challenge

EXPERIMENTAL

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

Biological: Lipopolysaccharide endotoxin

Interventions

Lipopolysaccharide endotoxin BIOLOGICAL

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

Also known as: (CCRE)LPS endotoxin from E. Coli 0:113 maintained by NIH

Challenge

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• John Sundy: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Study Officials

• John S Sundy, M.D., PhD.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 2, 2008
• First Posted: May 5, 2008
• Study Start: September 1, 2001
• Primary Completion: August 1, 2006
• Study Completion: April 1, 2008
• Last Updated: July 16, 2013

Record last verified: 2013-07

Locations

US (1)