Allergic Airway Disease
Conditions
Keywords
DEP, Broccoli Sprout Extract, Allergies
Brief summary
Allergic airway disease is a term used to describe conditions such as allergic rhinitis and asthma. Among other causative agents, air pollutants and diesel exhaust in particular, have been shown to create and also worsen existing allergic airway disease. These inhaled pollution particles have oxidative properties that drive inflammation-related effects through specific metabolic-associated processes. These processes are not adequately suppressed by current therapeutics. The purpose of this study is to explore the effects of broccoli sprout extract on the inflammatory process in the nose caused by diesel exhaust particles, which are important elements in air pollution. Broccoli sprout extract is a very potent inducer of Phase II enzymes (natural antioxidants).
Detailed description
Antioxidant enzymes are proteins produced by the body to protect cells against the harmful effects of chemicals, such as those found in air pollution. Particulate air pollution and diesel exhaust in particular have been shown to cause and also exacerbate allergic airway disease. While there are ongoing efforts to improve air quality, there remains a need for alternative methods to address and prevent the adverse health effects of ambient air pollution, such as allergic rhinitis,, asthma, chronic obstructive pulmonary disease, and lung cancer. Currently, there are no therapeutic options which, directly target and address the effects of air pollutants in susceptible populations. The purpose of this study is to examine the effect of broccoli sprout extract on airway inflammation caused by diesel exhaust particles. This study will analyze whether broccoli sprout extract will increase the levels of the natural, helpful, antioxidant enzymes in the nose and as a result decrease the inflammation caused by nasal exposure to diesel exhaust particles. Participants will attend up to ten clinical visits, which include three screening visits. Some visits (2, 4, and 9) will last approximately 1 hour and require that the participants return to the clinic after 6 hours. The remaining visits (excluding Visit 1, which will also last about 1 hour) will take less than 30 minutes. Participants are restricted from consuming certain vegetables three days prior to, and during the course of the study. During the screening phase, which will last from 4-5 days, and after giving informed consent participants will undergo a baseline evaluation that includes a medical history, a physical exam, blood drawing, allergy skin testing, nose washing, and a diesel exhaust particle (DEP) challenge test. For the DEP test, a small amount of fluid containing DEP particles will be sprayed in the nose (this amount is equivalent to the DEP that one breathes in over 2 days in Los Angeles). Investigators will also screen for natural antioxidant-related genes antioxidant enzymes and other indicators of DEP sensitivity. Female participants of child bearing potential will have a urine pregnancy test. Participants will be asked to drink broccoli sprout extract for four days in a row (visits 6, 7, 8, and 9). The dosage is less than 1 cup and requires that participants fast 2 hours before the study visits when broccoli sprout extract is ingested. This study requires that participants be allergic to cat. An allergy skin test will be performed to determine whether they have this kind of allergy.
Interventions
BSE will be ingested by drinking a liquid formula containing 1.25 g BSE in a volume equaling 1 cup daily for 4 consecutive days in the BSE intervention phase.
Sponsors
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Able and willing to provide informed consent * DEP responder as defined in protocol * Ability to refrain from consuming cruciferous vegetables 3 days prior to starting study and while on study. Cruciferous vegetables include: Broccoli, Kale, Chard, Kohlrabi, Brussels Sprouts, Parsley, Watercress, Daikon, Cabbage, Rutabagas, Cauliflower, Bok Choy, Arugula, Turnips, Radish, Mustard and Collard greens. * Allergy skin test positive to cat * Nonsmoker or ex-smoker of more than one year
Exclusion criteria
* Smoking within past year or during study * Systemic corticosteroid or other immunosuppressive medication use in the previous 3 months or during study * Intranasal corticosteroid use in the previous month or during the study * Intranasal antihistamine or cromolyn use in the previous week or during study * Allergen immunotherapy during the previous 12 months or during study * Omalizumab use in the previous 12 months or during study * Systemic antihistamine or leukotriene modifying medication use in the previous week or during study * History of asthma or any current medical condition that in the opinion of the investigator may compromise the subject's ability to safely participate in the study * Baseline abnormality of hemoglobin, platelets, leukocytes, serum chemistries, liver function testing, or presence of proteinuria * A finding during physical examination that, in the opinion of the investigator may compromise the participant's ability to safely participate in the study * Pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 0, 6 and 24 hours at Control visit and BSE visit (Day 4 of intervention) | Change of total nasal cell count in response to a standard diesel exhaust particle (DEP) challenge was determined by counting the total number of cells (leukocytes) recovered from nasal lavage fluid at 0 hr (just prior to DEP dosing), 6 hr and 24 hr later in participants who consuming BSE for 4 days, or without consuming BSE (control). Nasal challenges were performed with 300 microgram a standard DEP in 200 microliter saline. |
Countries
United States
Participant flow
Recruitment details
The enrollment period was 07/10/2009 - 11/09/2010. Enrollment took place in a private setting in the clinic located at the site.
Pre-assignment details
Thirty-eight participants who tested positive for cat allergy were enrolled. The study had three phases: screen, control and intervention. There was a 2-week run in and a 4-week wash out period. Six subjects who did not respond to DEP challenge at screen phase, and three subjects who withdrew from the study before intervention were excluded.
Participants by arm
| Arm | Count |
|---|---|
| DEP Challenge in Subjects Consuming BSE DEP will be administered in nostrils of participants who receive BSE by drinking 1 cup of liquid containing 1.25 g BSE daily for 4 days, or without consuming BSE. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | did not respond to DEP challe | 6 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | DEP Challenge in Subjects Consuming BSE |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Region of Enrollment United States | 29 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 38 |
| serious Total, serious adverse events | 5 / 38 |
Outcome results
Primary
Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention
Change of total nasal cell count in response to a standard diesel exhaust particle (DEP) challenge was determined by counting the total number of cells (leukocytes) recovered from nasal lavage fluid at 0 hr (just prior to DEP dosing), 6 hr and 24 hr later in participants who consuming BSE for 4 days, or without consuming BSE (control). Nasal challenges were performed with 300 microgram a standard DEP in 200 microliter saline.
Time frame: 0, 6 and 24 hours at Control visit and BSE visit (Day 4 of intervention)
Population: All participants with baseline (0 hr), and 6 hr and 24 hr post-baseline nasal cell count measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nasal DEP Challenge | Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 0 hr prior DEP dosing (control) | 4.44 log cells/mL | Standard Deviation 0.51 |
| Nasal DEP Challenge | Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 6 hr after DEP dosing (control) | 4.50 log cells/mL | Standard Deviation 0.56 |
| Nasal DEP Challenge | Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 24 hr after DEP dosing (control) | 4.73 log cells/mL | Standard Deviation 0.52 |
| Nasal DEP Challenge | Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 0 hr prior to DEP doising with BSE intervention | 4.70 log cells/mL | Standard Deviation 0.54 |
| Nasal DEP Challenge | Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 6 hr after DEP dosing with BSE intervention | 4.44 log cells/mL | Standard Deviation 0.51 |
| Nasal DEP Challenge | Total Nasal Cell Count in Response to DEP Challenge at 0, 6 and 24 hr With or Without BSE Intervention | 24 hr after DEP dosing with BSE intervention | 4.57 log cells/mL | Standard Deviation 0.46 |
Comparison: Comparison was made to the 24 h minus baseline change in both control phase and intervention phase.p-value: <0.001ANOVA
Comparison: Comparison waws made to the 6 hour minus baseline change in both control phase and intervention phase.p-value: <0.01ANOVA