Genetics of Asthma - Bronchoscopy Studies

NCT00644514 | Terminated Phase 1

• 2 other identifiers: Pro0000116612496-CP-001A
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify the mediators and genes in airway epithelial and BAL cells that are differentially regulated following inhalation of endotoxin lipopolysaccharide (LPS) among study participants with allergic asthma and normal phenotypes. This approach is designed to identify novel genes associated with both asthma pathogenesis and asthma susceptibility. LPS, or endotoxin, a cell wall component of gram-negative bacteria, is ubiquitous in the environment, and is thought to influence both susceptibility and severity of asthma. 240 subjects (healthy adult men and women (age \>18-40) with and without atopy and asthma) will complete the screening evaluations in order to establish 3 study groups of 60 subjects each. Each qualified subject will undergo an inhaled LPS endotoxin challenge followed by bronchoscopy after 24 hours, which will consist of a bronchoalveolar lavage (BAL) and endobronchial brush biopsies. BAL involves squirting a small amount of sterile salt water into one of the airways then gently taking it back out through the bronchoscope. The brush sample involves gently moving a small brush back and forth in an airway to collect cell samples. Samples of whole blood will also be obtained at various time points. RNA will be isolated from these cell populations in order to assess differential gene expression expression using microarrays.

Conditions

Atopic Asthma; Healthy

Keywords

LPS endotoxin; Asthma

Outcome Measures

Primary Outcomes (1)

• Identify Genes in airway epithelial and Bronchoalveolar Lavage (BAL)that are differentially regulated following inhalation of LPS endotoxin.

  bronchoscopy performed 24 hours after inhalation of endotoxin

Secondary Outcomes (1)

• Identify mediators in airway epithelial and BAL cells that are differentially regulated following LPS inhalation.

  Bronchoscopy performed 24 hours post inhalation of endotoxin

Study Arms (1)

LPS endotoxin inh f/u bronchoscopy

EXPERIMENTAL

Participants receive inhalation of LPS endotoxin, followed by bronchoscopy in this study.

Biological: Endotoxin - lipopolysaccharide (LPS)

Interventions

Endotoxin - lipopolysaccharide (LPS) BIOLOGICAL

Nebulized 5000EU, 10,000EU, 20,000EU endotoxin doses delivered to completion. Nebulized dose inhaled 30 minutes apart if no adverse events occur after the previous dose. Fiberoptic Bronchoscopy with Bronchoalveolar Lavage (BAL) and brush samples performed 24 hours after LPS nebulization.

Also known as: Lipopolysaccharide (LPS), NIH Clinical Center Reference Endotoxin

LPS endotoxin inh f/u bronchoscopy

Eligibility Criteria

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

You may qualify if:

• Allergic asthmatic, allergic non-asthmatic, or nonallergic nonasthmatic
• Willing/able to give informed consent \& adhere to visit/protocol schedules.
• Screening visit laboratory, C-Xray, EKG, results within normal limits
• Women of childbearing potential must have a negative serum pregnancy test
• Screening Pulmonary function testing above study criteria parameters

You may not qualify if:

• Systemic corticosteroid administration for asthma within the previous 90days
• Antibiotic administration within the previous 30 days.
• Viral respiratory infection within the previous 14 days.
• History of severe asthma requiring intubation.
• Occupational exposure to hay or grain dust.
• Significant exposure history to cigarette smoke
• Past or present history of allergen immunotherapy to within the last 10 yrs
• Underlying illnesses that may result in altered lung function
• Students or employees under direct supervision by protocol investigators are ineligible
• Subjects allergic to medications used (or potentially used) in the study will be excluded.
• Subjects using aspirin will be excluded
• Subjects who abuse alcohol or illicit substances will be excluded
• Medication use other than for asthma, allergies or contraception
• Other medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
• Nursing mothers

Sponsors & Collaborators

• John Sundy: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

Lipopolysaccharides

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

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: March 24, 2008
• First Posted: March 26, 2008
• Study Start: September 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: July 16, 2013

Record last verified: 2013-07

Locations

US (1)