Rhinitis,Allergic
Conditions
Keywords
hypersensitivity, antioxidants
Brief summary
Allergic rhinitis is a common illness suffered among US Veterans. There are medications that help relieve allergy symptoms, including nasal steroid sprays and antihistamines. Some patients have increase symptoms with exposure to their trigger, such as a grasses when combined with pollution due to oxidative stress from pollution. In this study, patients with allergic rhinitis to grass will be given broccoli sprout extract that contains an antioxidant sulforaphane do see if there is beneficial effect in these patients.
Detailed description
Allergic rhinitis is a common illness suffered among US Veterans. Despite the availability of medications, many patients fail to get adequate control of symptoms especially in high pollutant areas. Southern California air pollutants, like diesel exhaust particles may act as adjuvants to allergens leading to an exaggerated allergic response in certain individuals. These individuals may lack adequate Glutathione transferase activity; necessary to protect cells against pollutant induced oxidative stress. Sulforaphane has been shown to protect against oxidative stress. The investigators hypothesize consumption of foods containing high levels of sulforaphane are beneficial to US Veterans with GST deficiencies suffering from allergic rhinitis. In the investigators' preliminary data, the investigators discovered administration of broccoli sprout extract rich in sulforaphane leads to diminished nasal inflammatory reaction brought on by diesel exhaust particles though did not have sufficient patient numbers to prove an association with GST deficiency. The investigators propose a 3 week randomized clinical trial comparing broccoli sprout extract consumption with nasal corticosteroid administration after subjects with allergic rhinitis undergo a Timothy, Bermuda or Johnson grass nasal challenge. In Aims 1 and 2, the investigators will compare clinical (nasal symptom scores and peak nasal inspiratory flows) and laboratory (inflammatory cytokines, eosinophil cationic protein, tryptase) measurements between four groups: nasal corticosteroid, broccoli sprout extract, nasal corticosteroid plus broccoli sprout extract, and placebo. Aim 3 focuses on exploratory genetic analysis of the 3 glutathione S-transferase (GST) genes to determine if correlations exist between the inability to produce GST enzyme and the response to broccoli sprout extract. At the conclusion of this study, the investigators will gain further knowledge of which patients benefit from anti-oxidant nutritional supplementation in treating allergic rhinitis.
Interventions
DIETARY_SUPPLEMENTBroccoli Sprout Extract
Broccoli Sprout Extract contains the antioxidant Sulforaphane which is the active ingredient being studies.
fluticasone is a nasal steroid that is currently approved for treatment of allergic rhinitis.
DIETARY_SUPPLEMENTbroccoli sprout extract placebo
a tablet similar to the actual broccoli sprout extract though without BSE.
normal saline to replace nasal fluticasone in specific arms of the study
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria 1. Females and males 18 years or older. 2. History consistent with seasonal allergic rhinitis consistent with grass allergy (symptoms during summer months, June through August, for at least two consecutive seasons). 3. Not currently taking any medications for allergic rhinitis. 4. Provide written informed consent. 5. Willing and able to comply with all aspects of the protocol.
Exclusion criteria
1. The subject has any uncontrolled or serious disease, or any medical or surgical or condition that in the opinion of the investigator(s) could affect the subject's safety and/or interfere with the study assessments. 2. History of anaphylaxis to environmental allergens or an unknown trigger. 3. History of broccoli allergy 4. Recent upper respiratory infection (less than 4 weeks prior to study) or other active Infection. 5. Active smoker 6. Currently receiving allergy immunotherapy. 7. History of rhinitis exacerbation within the past 2 weeks. 8. Use of non-selective Beta-Blocker. 9. Inability to give written informed consent. 10. History or evidence of non-stable cognitive capacity within less than 1 year (i.e. Alzheimer's disease, dementia, bipolar disorder) that in the opinion of the investigator(s) could affect the subject's safety and/or interfere with the study assessments. 11. Pregnancy 12. Perennial rhinitis 13. Uncontrolled asthma 14. Forced Expiratory Volume in 1 second \<70% predicted at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Symptom Score (TNSS) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | measures at various points following challenge at baseline and 21 days | The Immediate Total Nasal Symptom Score (TNSS): The TNSS has been used in prior interventional studies to evaluate different treatment modes for allergic rhinitis. The score will consist of subjects rating 4 symptoms (nasal congestion/postnasal drainage, nasal pruritus, rhinorrhea, or sneezing) on a scale of 0 to 3, where 0=no symptoms present, 1=mild symptoms that do not interfere with activity, 2=moderate symptoms that are slightly bothersome symptoms with slight interference with activity and/or nighttime sleep, or 3=severe symptoms with interference with activity and nighttime sleep. Thus minimal value would be 0 vs. maximal value would be a score of 12. A higher score correlates with higher rhinitis activity. Diminished scores following an intervention is consistent with an improvement in rhinitis symptoms. |
| Peak Nasal Inspiratory Flow (PNIF) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | 21 days (from randomization to completion) | peak nasal inspiratory flow (PNIF) measures the peak flow during nasal inspiration with an approved device utilized in other studies. Measurements will be performed with TNSS (above). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interleukin 6 (IL6) | 21 days (from randomization to completion) | Interleukin 6 is a cytokine present during inflammatory process. This is recorded in pg/ml. Below is the log transformation of the pg/ml unit. Note that measurements are on a continuous score. Lower values are consistent with less inflammation which could occur with an inflammatory response. |
| Interleukin 8 (IL8) | 21 days (from randomization to completion) | Interleukin 8 s a cytokine that will increase with inflammation. Below is the log transformation of the pg/ml unit. Note that measurements are on a continuous score. Lower values are consistent with less inflammation which could occur with an inflammatory response. |
| Interleukin 5 (IL5) | 21 days (from randomization to completion) | Interleukin 5 (IL5) is considered a T2 cytokine that increases with exacerbations of atopic disease, including allergic rhinitis. Cytokine measurements are in pg/ml. Values are recorded with log transformation. Note that measurements are on a continuous score. Lower values are consistent with less T2 inflammation which is consistent with diminished or lower atopic/allergic response. |
| Interleukin 1 Beta (IL1b) | 21 days (from randomization to completion) | IL1b is a cytokine that will increase with inflammation. Below is the log transformation of the pg/ml unit. Note that measurements are on a continuous score. Lower values are consistent with less inflammation which could occur with an inflammatory response. |
| Interleukin 13 (IL13) | 21 days (from randomization to completion) | Interleukin 13 (IL13) is considered a T2 cytokine that increases with exacerbations of atopic disease, including allergic rhinitis. Cytokine measurements are in pg/ml. Values are recorded with log transformation. Note that measurements are on a continuous score. Lower values are consistent with less T2 inflammation which is consistent with diminished or lower atopic/allergic response. |
| Interleukin 4 (IL4) | 21 days (from randomization to completion) | Interleukin 4 (IL4) is considered a T2 cytokine that increases with exacerbations of atopic disease, including allergic rhinitis. Cytokine measurements are in pg/ml. Values are recorded with log transformation. Note that measurements are on a continuous score. Lower values are consistent with less T2 inflammation which is consistent with diminished or lower atopic/allergic response. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the VA Greater Los Angeles Healthcare System Allergy Immunology Clinic
Participants by arm
| Arm | Count |
|---|---|
| BSE + Nasal Fluticasone subjects will be randomized into 1 of 4 arms:
1. BSE + Nasal Fluticasone
2. BSE + normal saline nasal spray
3. Placebo Pill + Nasal Fluticasone
4. Placebo Pill + normal saline nasal spray
Broccoli Sprout Extract: Broccoli Sprout Extract contains the antioxidant Sulforaphane which is the active ingredient being studies.
fluticasone nasal: fluticasone is a nasal steroid that is currently approved for treatment of allergic rhinitis. | 16 |
| BSE + Normal Saline Nasal Spray subjects will be randomized into 1 of 4 arms:
1. BSE + Nasal Fluticasone
2. BSE + normal saline nasal spray
3. Placebo Pill + Nasal Fluticasone
4. Placebo Pill + normal saline nasal spray
Broccoli Sprout Extract: Broccoli Sprout Extract contains the antioxidant Sulforaphane which is the active ingredient being studies.
normal saline nasal spray: normal saline to replace nasal fluticasone in specific arms of the study | 14 |
| Placebo Pill + Nasal Fluticasone subjects will be randomized into 1 of 4 arms:
1. BSE + Nasal Fluticasone
2. BSE + normal saline nasal spray
3. Placebo Pill + Nasal Fluticasone
4. Placebo Pill + normal saline nasal spray
fluticasone nasal: fluticasone is a nasal steroid that is currently approved for treatment of allergic rhinitis.
broccoli sprout extract placebo: a tablet similar to the actual broccoli sprout extract though without BSE. | 9 |
| Placebo Pill + Normal Saline Nasal Spray subjects will be randomized into 1 of 4 arms:
1. BSE + Nasal Fluticasone
2. BSE + normal saline nasal spray
3. Placebo Pill + Nasal Fluticasone
4. Placebo Pill + normal saline nasal spray
broccoli sprout extract placebo: a tablet similar to the actual broccoli sprout extract though without BSE.
normal saline nasal spray: normal saline to replace nasal fluticasone in specific arms of the study | 8 |
| Total | 47 |
Baseline characteristics
| Characteristic | BSE + Normal Saline Nasal Spray | Placebo Pill + Nasal Fluticasone | Placebo Pill + Normal Saline Nasal Spray | Total | BSE + Nasal Fluticasone |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 1 Participants | 8 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 5 Participants | 7 Participants | 39 Participants | 15 Participants |
| PNIF | 120 L/min STANDARD_DEVIATION 14.1 | 172.5 L/min STANDARD_DEVIATION 31.8 | 170 L/min STANDARD_DEVIATION 28.3 | 155 L/min STANDARD_DEVIATION 49.5 | 105 L/min STANDARD_DEVIATION 21.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 4 Participants | 17 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 3 Participants | 3 Participants | 21 Participants | 7 Participants |
| Region of Enrollment United States | 14 Participants | 9 Participants | 8 Participants | 47 Participants | 16 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 3 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 5 Participants | 35 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 14 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 3 / 16 | 4 / 14 | 0 / 9 | 2 / 8 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Peak Nasal Inspiratory Flow (PNIF) Change From Baseline to 3 Weeks of Randomly Assigned Treatment
peak nasal inspiratory flow (PNIF) measures the peak flow during nasal inspiration with an approved device utilized in other studies. Measurements will be performed with TNSS (above).
Time frame: 21 days (from randomization to completion)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Peak Nasal Inspiratory Flow (PNIF) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | .3362 L/min | Standard Deviation 0.0026 |
| BSE + Normal Saline Nasal Spray | Peak Nasal Inspiratory Flow (PNIF) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | .1213 L/min | Standard Deviation 0.0607 |
| Placebo Pill + Nasal Fluticasone | Peak Nasal Inspiratory Flow (PNIF) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | .0636 L/min | Standard Deviation 0.0485 |
| Placebo Pill + Normal Saline Nasal Spray | Peak Nasal Inspiratory Flow (PNIF) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | -.0538 L/min | Standard Deviation 0.0453 |
Primary
Total Nasal Symptom Score (TNSS) Change From Baseline to 3 Weeks of Randomly Assigned Treatment
The Immediate Total Nasal Symptom Score (TNSS): The TNSS has been used in prior interventional studies to evaluate different treatment modes for allergic rhinitis. The score will consist of subjects rating 4 symptoms (nasal congestion/postnasal drainage, nasal pruritus, rhinorrhea, or sneezing) on a scale of 0 to 3, where 0=no symptoms present, 1=mild symptoms that do not interfere with activity, 2=moderate symptoms that are slightly bothersome symptoms with slight interference with activity and/or nighttime sleep, or 3=severe symptoms with interference with activity and nighttime sleep. Thus minimal value would be 0 vs. maximal value would be a score of 12. A higher score correlates with higher rhinitis activity. Diminished scores following an intervention is consistent with an improvement in rhinitis symptoms.
Time frame: measures at various points following challenge at baseline and 21 days
Population: intent to treat population (all participants assigned to 1 of the 4 groups above).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Total Nasal Symptom Score (TNSS) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | -.5277 score on a scale | Standard Deviation 0.1048 |
| BSE + Normal Saline Nasal Spray | Total Nasal Symptom Score (TNSS) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | -.5484 score on a scale | Standard Deviation 0.0014 |
| Placebo Pill + Nasal Fluticasone | Total Nasal Symptom Score (TNSS) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | -.8359 score on a scale | Standard Deviation 0.3903 |
| Placebo Pill + Normal Saline Nasal Spray | Total Nasal Symptom Score (TNSS) Change From Baseline to 3 Weeks of Randomly Assigned Treatment | -.181 score on a scale | Standard Deviation 0.0846 |
Secondary
Interleukin 13 (IL13)
Interleukin 13 (IL13) is considered a T2 cytokine that increases with exacerbations of atopic disease, including allergic rhinitis. Cytokine measurements are in pg/ml. Values are recorded with log transformation. Note that measurements are on a continuous score. Lower values are consistent with less T2 inflammation which is consistent with diminished or lower atopic/allergic response.
Time frame: 21 days (from randomization to completion)
Population: Patient diagnosed with grass induced allergic rhinitis were randomized into 1 of 4 groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Interleukin 13 (IL13) | -1.0822 log(pg/ml) | Standard Deviation 0.2568 |
| BSE + Normal Saline Nasal Spray | Interleukin 13 (IL13) | -.2985 log(pg/ml) | Standard Deviation 0.0466 |
| Placebo Pill + Nasal Fluticasone | Interleukin 13 (IL13) | .1577 log(pg/ml) | Standard Deviation 0.1042 |
| Placebo Pill + Normal Saline Nasal Spray | Interleukin 13 (IL13) | -.0459 log(pg/ml) | Standard Deviation 0.3745 |
Secondary
Interleukin 1 Beta (IL1b)
IL1b is a cytokine that will increase with inflammation. Below is the log transformation of the pg/ml unit. Note that measurements are on a continuous score. Lower values are consistent with less inflammation which could occur with an inflammatory response.
Time frame: 21 days (from randomization to completion)
Population: Patient diagnosed with grass induced allergic rhinitis were randomized into 1 of 4 groups
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Interleukin 1 Beta (IL1b) | -.4058 pg/ml with log transformation | Standard Deviation 0.2563 |
| BSE + Normal Saline Nasal Spray | Interleukin 1 Beta (IL1b) | .0183 pg/ml with log transformation | Standard Deviation 0.037 |
| Placebo Pill + Nasal Fluticasone | Interleukin 1 Beta (IL1b) | -.2382 pg/ml with log transformation | Standard Deviation 0.3013 |
| Placebo Pill + Normal Saline Nasal Spray | Interleukin 1 Beta (IL1b) | .0713 pg/ml with log transformation | Standard Deviation 0.1139 |
Secondary
Interleukin 4 (IL4)
Interleukin 4 (IL4) is considered a T2 cytokine that increases with exacerbations of atopic disease, including allergic rhinitis. Cytokine measurements are in pg/ml. Values are recorded with log transformation. Note that measurements are on a continuous score. Lower values are consistent with less T2 inflammation which is consistent with diminished or lower atopic/allergic response.
Time frame: 21 days (from randomization to completion)
Population: Patient diagnosed with grass induced allergic rhinitis were randomized into 1 of 4 groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Interleukin 4 (IL4) | -.5655 log(pg/ml) | Standard Deviation 0.4738 |
| BSE + Normal Saline Nasal Spray | Interleukin 4 (IL4) | -.1076 log(pg/ml) | Standard Deviation 0.0228 |
| Placebo Pill + Nasal Fluticasone | Interleukin 4 (IL4) | -.3682 log(pg/ml) | Standard Deviation 0.0294 |
| Placebo Pill + Normal Saline Nasal Spray | Interleukin 4 (IL4) | -.3695 log(pg/ml) | Standard Deviation 0.233 |
Secondary
Interleukin 5 (IL5)
Interleukin 5 (IL5) is considered a T2 cytokine that increases with exacerbations of atopic disease, including allergic rhinitis. Cytokine measurements are in pg/ml. Values are recorded with log transformation. Note that measurements are on a continuous score. Lower values are consistent with less T2 inflammation which is consistent with diminished or lower atopic/allergic response.
Time frame: 21 days (from randomization to completion)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Interleukin 5 (IL5) | -.5285 log(pg/ml) | Standard Deviation 0.2236 |
| BSE + Normal Saline Nasal Spray | Interleukin 5 (IL5) | -.3213 log(pg/ml) | Standard Deviation 0.2005 |
| Placebo Pill + Nasal Fluticasone | Interleukin 5 (IL5) | -.1082 log(pg/ml) | Standard Deviation 0.0083 |
| Placebo Pill + Normal Saline Nasal Spray | Interleukin 5 (IL5) | -.3755 log(pg/ml) | Standard Deviation 0.1866 |
Secondary
Interleukin 6 (IL6)
Interleukin 6 is a cytokine present during inflammatory process. This is recorded in pg/ml. Below is the log transformation of the pg/ml unit. Note that measurements are on a continuous score. Lower values are consistent with less inflammation which could occur with an inflammatory response.
Time frame: 21 days (from randomization to completion)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Interleukin 6 (IL6) | -1.0868 log(pg/ml) | Standard Deviation 0.2903 |
| BSE + Normal Saline Nasal Spray | Interleukin 6 (IL6) | -.0519 log(pg/ml) | Standard Deviation 0.2437 |
| Placebo Pill + Nasal Fluticasone | Interleukin 6 (IL6) | -.2719 log(pg/ml) | Standard Deviation 1.6894 |
| Placebo Pill + Normal Saline Nasal Spray | Interleukin 6 (IL6) | .3567 log(pg/ml) | Standard Deviation 0.2826 |
Secondary
Interleukin 8 (IL8)
Interleukin 8 s a cytokine that will increase with inflammation. Below is the log transformation of the pg/ml unit. Note that measurements are on a continuous score. Lower values are consistent with less inflammation which could occur with an inflammatory response.
Time frame: 21 days (from randomization to completion)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BSE + Nasal Fluticasone | Interleukin 8 (IL8) | -.7626 pg/ml log transformation | Standard Deviation 0.0168 |
| BSE + Normal Saline Nasal Spray | Interleukin 8 (IL8) | -.047 pg/ml log transformation | Standard Deviation 0.0033 |
| Placebo Pill + Nasal Fluticasone | Interleukin 8 (IL8) | -.1013 pg/ml log transformation | Standard Deviation 0.2629 |
| Placebo Pill + Normal Saline Nasal Spray | Interleukin 8 (IL8) | .0472 pg/ml log transformation | Standard Deviation 0.1748 |