Functional Implications of TNF

NCT00729131 | Completed

• 1 other identifier: 00008547
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The research plan proposes to develop translational studies in humans that will identify host susceptibility factors that confer vulnerability to the prototypal air pollutant, ozone. Ozone is a ubiquitous urban air pollutant and associated with increased emergency room visits, and co-associates with other air pollutants, to increase mortality in high risk groups (cardio-pulmonary disease) of the population.The results will have significant impact upon and aid in understanding mechanisms of pro-oxidant lung injury, airway hyperresponsiveness, and adverse health effects, that occur during and following exposure to inhalable airborne irritants.

Conditions

Bronchitis

Keywords

Ozone, TNF, TNF promoter polymorphism, airway hyperresponsiveness.

Outcome Measures

Primary Outcomes (1)

• biologic response to ozone exposure: bronchoalveolar lavage fluid analyzed for inflammatory cytokines, cell differentials, and activated alveolar macrophages.

  Lung lavage evaluated 20 hr post-exposure to ozone.

Secondary Outcomes (1)

• Alveolar macrophages (collected in lung lavage fluid) will be studied ex vivo for activation state and pro-inflammatory cytokine secretion.

  20 hr post-exposure to ozone.

Study Arms (2)

A

Control group: subjects are homozygotic for major allele for TNF-308 promoter polymorphism.

Drug: Etanercept inhibition of ozone-induced airway hyper-responsiveness.

B

Case Group: subjects are homozygotic or heterozygotic for minor allele of TNF-308 promoter polymorphism.

Interventions

Etanercept inhibition of ozone-induced airway hyper-responsiveness. DRUG

Single dosage of etanercept(50 mg, subcutaneous) given 2 days prior to a laboratory ozone exposure.

Also known as: Only a single group of subjects, known to demonstrate airway hyperresponsiveness at 20 hr post exposure to ozone will be studied in the, intervention.

A

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Healthy non-smokers (18-35 yr) will be recruited from the Duke campus and local community; 50% will be women. Subjects will have a clinical history and lung function screening at protocol entry. Female subjects of childbearing age will have pregnancy testing. We will only recruit subjects with a normal body habitus as an increased BMI may modify sensitivity to O3. Subjects will have lung volumes within predicted normal, and FEV1, and FEF25-75, within range of predicted, and methacholine response less than the mean Mch PC20 dose for non-asthmatic population in our human inhalation laboratory. Atopic status of study subjects will be determined by lack of positive skin test by prick technique (using panel of antigens common to central NC) and without seasonal or perennial allergic symptoms.

You may not qualify if:

• subjects with current or past smoking history, acute respiratory illness within six weeks of the study, and significant non-pulmonary disease as determined by the investigator, pregnancy, age \<18 or \>35 yr, or inability to understand the protocol. Subjects will be requested to refrain from anti-histamines, nonsteroidal anti-inflammatory agents, and supplemental vitamins, e.g. C and E, for 1 week prior to, and during lab visits for exposures and follow-up measures.

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bronchoalveolar lavage specimens.

MeSH Terms

Conditions

Bronchitis; Respiratory Hypersensitivity

Interventions

Methods

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 6, 2008
• First Posted: August 7, 2008
• Study Start: August 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: February 1, 2012
• Last Updated: September 29, 2014

Record last verified: 2014-09

Locations

US (1)