A Study of Inhalation of 20,000 EU CCRE in Normal Volunteers Compared to Allergic Asthmatic Individuals
- Conditions
- AsthmaHypersensitivity
- Interventions
- Biological: Clinical Center Reference Endotoxin (CCRE)
- Registration Number
- NCT00839124
- Lead Sponsor
- University of North Carolina, Chapel Hill
- 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.
- Detailed Description
This will be a single center, open label study of allergic asthmatic and normal volunteers. The protocol will compare baseline characteristics of recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after inhalational challenge with CCRE within each group as well as cross group comparisons between AA's and NV's. The following information indicates procedures to be performed at each visit as well as the anticipated duration of visits. Subsequent to this description are details regarding specific study procedures.
Visit 1: Baseline Visit (5 hours)
1. Consent will be obtained, review of subject's medical history, current medications and inclusion/exclusion criteria.
2. Vital sign measurements (temperature, pulse, respiratory rate, blood pressure), oxygen saturation, and symptom scoring
3. Urine pregnancy test for women of child bearing potential
4. Spirometry
5. Venipuncture for CBC with differential and baseline blood analyses
6. Physical exam of the ears, nose, throat and chest
7. Collection of exhaled breath for measurement of nitric oxide level
8. Xenon equilibrium gas scan and MCC
9. MCC scan
10. Sputum induction
11. After completion of the sputum induction, subjects will have brief MCC scan (\< 10 minutes)
Visit 2: 24 hours post baseline subjects will return for the following 1 hour visit:
1. Review any change in medical status over prior 24 hours, vital signs, O2 saturation and symptom score
2. Follow up MCC scan
Visit 3: 24-48 hours prior to challenge visit at least 2 days after the baseline visit (½ hour)
1. Review change in medical status since last visit; vital signs, oxygen saturation, \& symptom score
2. Urine pregnancy test
3. Spirometry
Visit 4: Endotoxin (CCRE) challenge day (8.5 to 9 hours)
1. Review any change in medical status since last visit
2. Vital signs, oxygen saturation, and symptom score
3. Spirometry
4. Physical exam of the ears, nose, throat and chest
5. If above measures are acceptable, CCRE challenge will be performed
6. Post-challenge monitoring including spirometry, vital signs, oxygen saturation, and symptom score at the following intervals post challenge: 30 and 60 minutes and then hourly for 5 additional hours.
7. Post challenge venipuncture (blood draw) for CBC with differential and post CCRE blood analyses
8. Collection of exhaled breath for measurement of nitric oxide level.
9. Four hours post challenge, subject will have MCC evaluated
10. After MCC is assessed, sputum induction will be performed.
11. After completion of the sputum induction, subjects will have brief MCC scan (\< 10 minutes)
12. Discharge home or, alternatively, to GCRC for overnight observation per study MD.
Visit 5: 24 hours post challenge visit (1 hour)
1. Subject returns to the CEMALB, vital signs, oxygen saturation, and symptom score
2. Collection of exhaled breath for measurement of nitric oxide level.
3. Spirometry
4. Follow-up MCC scan
5. Each volunteer will be given a symptom scoring sheet for each day up to 96 hours (4 days) after challenge (see accompanying symptom scoring sheet in Appendix 3).
Post Challenge Observations/Reporting (5 minutes)
1. Subjects will be contacted for phone call follow-up 48-96 hours after challenge (see script Appendix 4 of accompanying protocol)
Study discontinuation visit within 10 days of the challenge dose: (15 minutes)
1. Vital signs, O2 saturation, symptom score, spirometry
2. If any findings are abnormal, medical evaluation as directed by the study physician will be undertaken Appendix 1 of the accompanying protocol provides a summary table regarding procedures performed at each subject study visit
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Allergic asthma Clinical Center Reference Endotoxin (CCRE) subjects with allergic asthma will undergo challenge with 20,000 EU CCRE healthy control Clinical Center Reference Endotoxin (CCRE) Healthy volunteers will undergo challenge with 20,000 EU CCRE
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
UNC Center for Environmental Medicine, Asthma and Lung Biology
🇺🇸Chapel Hill, North Carolina, United States