A Study of Inhalation of 20,000 EU CCRE in Normal Volunteers Compared to Allergic Asthmatic Individuals

NCT00839124 | Completed Phase 1 DMC

• 2 other identifiers: 08-1750 (CTRC # 2776)5U19AI077437-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single center, open label study comparing baseline characteristics of recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after inhalational challenge with 20,000 EU Clinical Center Reference Endotoxin (CCRE, a component of air pollution)) within each group as well as cross group comparisons between individuals with allergic asthma (AA's)and normal volunteers (NV's). The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers. Secondary objectives include post CCRE comparison between AA's and NV's with regard to changes in airway cells and blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000 EU CCRE.

Conditions

Asthma; Hypersensitivity

Keywords

normal volunteer; healthy control volunteer; healthy subjects; asthma; allergy; allergic asthma

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to test the hypothesis that persons with allergic asthma will have an increased neutrophil response to challenge with 20,000 EU CCRE compared to normal volunteers

  6 hours post challenge

Secondary Outcomes (1)

• Secondary objectives include post CCRE comparison between AA's and NV's with regard to changes in airway cells and blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000 EU CCRE.

  6-24 hours post challenge

Study Arms (2)

Allergic asthma

ACTIVE COMPARATOR

subjects with allergic asthma will undergo challenge with 20,000 EU CCRE

Biological: Clinical Center Reference Endotoxin (CCRE)

healthy control

ACTIVE COMPARATOR

Healthy volunteers will undergo challenge with 20,000 EU CCRE

Biological: Clinical Center Reference Endotoxin (CCRE)

Interventions

Clinical Center Reference Endotoxin (CCRE) BIOLOGICAL

inhalation challenge with 20,000 EU CCRE

Also known as: air pollution

healthy control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal lung function, defined as (Knudson 1976/1984 predicted set):
• FVC of \> 80 % of that predicted for gender, ethnicity, age and height FEV1 of \> 80 % of that predicted for gender, ethnicity, age and height FEV1/FVC ratio of \> .75
• Oxygen saturation of \> 94 % and normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
• Symptom Score no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.
• Negative methacholine inhalation challenge as performed in the screening protocol. (Less than a 20% decrease in FEV1 at a maximum methacholine concentration of 10 mg/ml)
• Negative pregnancy test for females
• Negative allergy skin test (AST)
• History of episodic wheezing, chest tightness, or shortness of breath after age of 6 years consistent with asthma, or physician diagnosed asthma after age of 6 years.
• Positive methacholine test.
• FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .70 (without use of bronchodilating medications for 12 hours)
• Allergic sensitization to at least one of the following allergen preparations: (House Dust Mite f, House dust mite p, Cockroach, Tree mix, Grass Mix, Weed Mix, Mold Mix 1, Mold Mix 2, Rat, Mouse, Guinea Pig, Rabbit, Cat or Dog) confirmed by positive AST.
• Negative allergy skin test as performed in the screening protocol.

You may not qualify if:

• Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.
• Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
• Use of systemic steroid therapy within the preceding 12 months for an asthma exacerbation. All use of systemic steroids in the last year will be reviewed by a study physician.
• Use of inhaled steroids, cromolyn or leukotriene inhibitors (montelukast or zafirlukast) except for use of cromolyn exclusively prior to exercise.
• Use of daily theophylline within the past month.
• Use of tricyclics and MAO inhibitors
• Pregnancy or nursing a baby.
• Cigarette smoking \> 1 pack per month.
• Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
• Exacerbation of asthma more than 2x/week which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
• Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
• Viral upper respiratory tract infection within 2 weeks of challenge.
• Any acute infection requiring antibiotics within 2 weeks of challenge
• Receipt of LAIV (Live Attenuated Influenza Vaccine), also know as FluMist®, within the prior 14 days

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

UNC Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599-7310, United States

Location

Related Publications (2)

• Bennett WD, Alexis NE, Almond M, Herbst M, Zeman KL, Peden DB. Effect of inhaled endotoxin on mucociliary clearance and airway inflammation in mild smokers and nonsmokers. J Aerosol Med Pulm Drug Deliv. 2014 Dec;27(6):459-65. doi: 10.1089/jamp.2013.1089.

  PMID: 24568613 DERIVED

• Bennett WD, Herbst M, Zeman KL, Wu J, Hernandez ML, Peden DB. Effect of inhaled endotoxin on regional particle deposition in patients with mild asthma. J Allergy Clin Immunol. 2013 Mar;131(3):912-3. doi: 10.1016/j.jaci.2012.09.010. Epub 2012 Oct 25. No abstract available.

  PMID: 23102735 DERIVED

MeSH Terms

Conditions

Asthma; Hypersensitivity

Interventions

Air Pollution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Environmental Pollution; Public Health; Environment and Public Health

Study Officials

• David B Peden, MD, MS

  University of North Carolina at Chapel Hill, Dept of Pediatrics / Center for Environmental Medicine, Asthma and Lung Biology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: February 9, 2009
• Study Start: January 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 5, 2012

Record last verified: 2012-12

Locations

US (1)