Effect of a 10,000 EU Dose of Endotoxin in Allergic and Mildly Asthmatic Adults

NCT00839189 | Completed Phase 1

• 2 other identifiers: 02-1518 (GCRC 1983)NIH HL080337
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this pilot safety study are to identify a dose of inhaled Clinical Center Reference Endotoxin (CCRE) that is well tolerated by allergic subjects that induces measurable increases in neutrophil content of induced sputum that can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin.

Conditions

Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Asthma

Keywords

CCRE; endotoxin; LPS; asthma; allergies; allergic rhinitis

Outcome Measures

Primary Outcomes (1)

• Magnitude of change in neutrophil content of induced sputum after inhalation of 10,000 EU CCRE

  0-24 hours post challenge

Secondary Outcomes (1)

• change in PFT's, vital signs and symptom score after inhalation of 10,000 EU of CCRE

  0-24 hours post challenge

Interventions

Clinical Center Reference Endotoxin (CCRE) BIOLOGICAL

Inhalation of 10,000 EU CCRE

Also known as: LPS, endotoxin

Eligibility Criteria

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

You may qualify if:

• Specific allergy 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 immediate skin test response.
• FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .75 (without use of bronchodilating medications for 12 hours), consistent with lung function of persons with no more than mild episodic or mild persistent asthma.
• History of nasal allergy, including episodic, perennial, or seasonal sneezing, nasal congestion or cough, or such symptoms associated with specific exposures (such as cat or dog)
• Criteria for classification as having asthma with allergic rhinitis vs. allergic rhinitis alone:
• History of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician diagnosed asthma.
• Provocative concentration of methacholine producing a 20% fall in FEV1 (PC20 methacholine) of less than 10 mg/ml by the method used (see below).

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 zafirkulast) initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy and shown to be stable.
• Use of daily theophylline within the past month.
• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UNC Center for Environmental Medicine, Asthma and Lung Biology

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

Location

MeSH Terms

Conditions

Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Asthma; Hypersensitivity; Rhinitis, Allergic

Interventions

Endotoxins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• David Peden, MD

  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: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: February 9, 2009
• Study Start: October 1, 2002
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: December 9, 2009

Record last verified: 2009-12

Locations

US (1)