Clinical trial NCT02402465
Conditions: Allergic Rhinitis
Sponsor: University of Chicago
Start date: 2015-02-01; Completion date: 2020-02-01
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Dymista, a combined product containing the antihistamine azelastine and the intranasal steroid fluticasone, provides superior clinical efficacy to both fluticasone propionate and azelastine hydrochloride in the treatment of seasonal allergic rhinitis. The superiority of efficacy not only occurs at the initiation of treatment, but persists for its duration. The mechanism underlying the superior efficacy of Dymista is not known. This trial focuses on examining the effects of Dymista on the dynamics of the allergic response in man using nasal provocation with antigen. The investigators will study the relationship between symptoms, physiology, cells and mediators.

Detailed description:
The main hypothesis for the trial is that Dymista affects multiple phases of the allergic response, which in sum are greater than the effects of fluticasone propionate or azelastine hydrochloride alone.

Our objectives for this study are to demonstrate:

1. that the induction of allergic inflammation by nasal provocation with antigen causes a cellular infiltration, with subsequent release of inflammatory biomarkers that cause augmented responses to subsequent exposure to antigens.
2. that fluticasone prevents allergic inflammation from developing after antigen challenge and subsequently prevents the augmentation of the nasal response to nasal challenge with antigen.
3. that the azelastine in Dymista reduces the effects of released histamine

To address these hypotheses we will perform a 3-way, randomized, placebo-controlled, and crossover trial. We will recruit 20 asymptomatic seasonal allergic rhinitis patients outside of the relevant season. The subjects will receive placebo, fluticasone propionate and Dymista. The nasal provocations will be separated by 2 weeks. Treatment will begin 15 minutes before nasal provocation with ragweed or grass antigen and the treatment will continue twice a day for 3 days. Nasal provocation will occur daily for three days to evaluate for priming (increased sensitization with repeated antigen exposure, which mimics seasonal disease where antigen exposure occurs in the setting of continued allergic inflammation). For outcome measures, we will monitor both nasal symptoms after nasal provocation as well as collect nasal lavage to evaluate effects on eosinophils and biomarkers of the immune response. In the nasal lavage, we will quantify the number of eosinophils (a marker of cellular recruitment) and measure the levels of histamine (a marker of basophil and mast cell activation), tryptase (a marker of mast cell activation), albumin (a marker of vascular permeability), lactoferrin (a marker of glandular activation) and ECP (a marker of eosinophil activation). Thus we expect to generate information on both clinical effects and physiologic differences between the treatments.

Arms: arm 1: Placebo nasal spray that is similar to Dymista in all respects except the active ingredient arm 2: Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista arm 3: Dymista is also provided as a nasal spray in bottles similar to the other two agents
Interventions: intervention 1: Placebo intervention 2: Fluticasone propionate intervention 3: Fluticasone/Azelastine nasal spray intervention 4: Nasal Allergen Challenge
Intervention descriptions: intervention 1: Patients will be treated by placebo intervention 2: Patients will receive fluticasone nasal spray intervention 3: Patients will receive Dymista nasal spray intervention 4: All subjects will receive a nasal challenge with allergen to mimick an allergic response and allow the investigation of the different drug effects on that response. Allergen extracts will be used as sprays into the nasal cavity. The extracts are approved by FDA for skin testing or desensitization therapy and an IND was obtained to allow intranasal administration

Protocol documents:
Prot_SAP_000.pdf: 
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Dymista Proposal 
 
Rationale:  Dymista provides superior clinical efficacy to both fluticasone propionate and azelastine 
hydrochloride in the treatment of seasonal allergic rhinitis.  The superiority of efficacy not only occurs at 
the initiation of treatment, but persists for its duration.  The mechanism underlying the superior efficacy 
of Dymista is not known.  One can postulate many potential interactions between the components of 
Dymista overall as well as different effects of these interactions occurring during the course of treatment.  
This proposal focuses on examining the effects of Dymista on the dynamics of the allergic response in 
man using nasal provocation with antigen.  We will study the relationship between symptoms, 
physiology, cells and mediators.   
 
Hypothesis:  We hypothesize that Dymista affects multiple phases of the allergic response, which in sum 
are greater than the effects of fluticasone propionate or azelastine hydrochloride alone. 
 
Specific aims/objective:  Our objectives for this study are to demonstrate: 
1. that the induction of allergic inflammation by nasal provocation with antigen causes a cellular 
infiltration, with subsequent release of inflammatory biomarkers that cause augmented responses 
to subsequent exposure to antigens. 
2. that fluticasone prevents allergic inflammation from developing after antigen challenge and 
subsequently prevents the augmentation of the nasal response to nasal challenge with antigen. 
3. that the azelastine in Dymista reduces the effects of released histamine 
 
Methods (including study design):  We propose to perform a 3-way, randomized, placebo-controlled, and 
crossover trial.  We will recruit 20 asymptomatic seasonal allergic rhinitis patients outside of the relevant 
season.  The subjects will receive placebo, fluticasone propionate and Dymista.  The nasal provocations 
will be separated by 2 weeks.  Treatment will begin 15 minutes before nasal provocation with ragweed or 
grass antigen and the treatment will continue twice a day for 3 days.  Nasal provocation will occur daily 
for three days to evaluate for priming (increased sensitization with repeated antigen exposure, which 
mimics seasonal disease where antigen exposure occurs in the setting of continued allergic inflammation).  
For outcome measures, we will monitor both nasal symptoms after nasal provocation as well as collect 
nasal lavage to evaluate effects on eosinophils and biomarkers of the immune response.  In the nasal 
lavage, we will quantify the number of eosinophils (a marker of cellular recruitment) and measure the 
levels of histamine (a marker of basophil and mast cell activation), tryptase (a marker of mast cell 
activation), albumin (a marker of vascular permeability), lactoferrin (a marker of glandular activation) 
and ECP (a marker of eosinophil activation).  Thus we expect to generate information on both clinical 
effects and physiologic differences between the treatments.  
 
We will recruit normal healthy volunteers with grass and/or ragweed allergic rhinitis.  Based on previous 
experience, we anticipate screening about 55 subjects to have 20 complete this study.  After preliminary 
telephone contact, subjects will come to the nasal physiology laboratory for a screening visit.  At this 
visit, after signing consent, they will answer a nasal questionnaire, and undergo skin testing and nasal 
challenge with antigen.  Depending on skin test results, eligible subjects will then undergo nasal challenge 
with either grass or ragweed allergen outside their allergy season.  Female subjects will be asked to take a 
urine pregnancy test prior to enrollment.  Twenty subjects with a positive response, defined as 2 or more 
sneezes and an increase in symptom score after allergen challenge, will be recruited. 
 
 
Inclusion Criteria 
1. Males and females between 18 and 55 years of age. 
2. History of grass and/or ragweed allergic rhinitis. 
3. Positive skin test to grass and/or ragweed antigen. 
4. Positive response to screening nasal challenge. 


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5. Off all anti-allergic medications for a minimum of 2 weeks. 
 
Exclusion Criteria 
1. Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease. 
2. Pregnant or lactating women. 
3. Upper respiratory infection within 14 days of study start. 
 
Symptom Scores:  Symptom scores are recorded by subjects after each nasal challenge.  Subjects report 
four symptoms: sneezing, rhinorrhea, nasal congestion, and nasal itching on a scale from 0 to 3 (0= no 
symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms).  They will also count their 
sneezes and record them after each challenge.  
 
Subjects will come to the nasal physiology laboratory for antigen challenge after 2 weeks of washout.  On 
the day of experiment, the subjects will present to the laboratory and be allowed to rest for 15 minutes so 
that equilibration of the nasal mucosa with the environmental condition of the laboratory is achieved.  
Symptom score evaluation will be performed first as a baseline.  Then, 4 nasal lavages are performed to 
bring mediator levels to a stable baseline and combined for measurement of eosinophils.  After that, 
another nasal lavage (B1) is performed and kept as a baseline.  A nasal lavage involves instilling 2.5 ml of 
warmed (37C) lactated Ringer’s solution into each nostril and, after 10 seconds, the secretions are 
expelled into a plastic collection basin.  The returned volume ranges between 75%-85% of that instilled.  
All samples are vigorously shaken to homogenize the mixture of sol and gel phase and are stored on ice in 
plastic tubes until the experiment is done.  Next, oxymetazoline is applied topically to the nasal mucosa to 
prevent mucosal congestion that interferes with lavage.  Prior experiments have shown that 
oxymetazoline does not interfere with sneezing or histamine release.  After a 10-minute wait, the subjects 
will receive their first treatment.  Ten minutes later, a control challenge with the diluent used for the 
allergen extract (4% phenol buffer saline) will be performed by spray method.  Ten minutes later, 
symptom score evaluation and nasal lavage are repeated.  Then, antigen challenge with two increasing 
doses of antigen (The concentrations used for ragweed will be 1:200 w/v, and 1:66 w/v and for grass 
3333, and 6666 bioequivalent allergy unit BAU/mL).  The total amount delivered per challenge will be 2 
puffs (0.18 mL), 12 minutes apart, will be performed by the same method.  Ten minutes after each 
challenge, symptom score evaluation and nasal lavage are repeated in the same way as after diluent 
challenge. 
 
After the lavage that follows the last antigen challenge, the subjects will be discharged from the 
laboratory and instructed to return the following day.  They will also be instructed to use their spray at 
night.  When they arrive the next day, a symptom score evaluation and a lavage will be performed to 
evaluate for the late phase response.  They will receive the morning dose of the medication during the 
nasal challenge as on the first day of the nasal challenge.  This will be followed by a second challenge as 
on day 1.  The same will be repeated on the third day while the subjects are still receiving study 
medication.  The baseline lavage will be evaluated for eosinophils and the level of ECP, and all 
subsequent lavages are assayed for histamine, tryptase, albumin, and lactoferrin.     
 
The total number of cells in nasal lavage fluid will be counted using a hemocytometer.  The lavage is then 
placed on ice until centrifugation at 5,000 rpm for 15 minutes at 4C.  The cell pellet is resuspended in an 
adequate volume of buffer and cytospun onto one or more slides.  The cells will then be dried, fixed and 
stained with Diff-Quick Stain to allow enumeration of different types of cells.  The percentage of 
eosinophils is counted and the total number of eosinophils is calculated by multiplying that percentage by 
the total cell count.  Two hundred cells will be counted.  If the number of countable cells is more than 50, 
but there are no eosinophils, the total number of eosinophils will be assigned a number equivalent to the 
lowest number of eosinophils obtained from counting an acceptable and technically adequate slide.  This 


Page 3 of 5 
V08.21.17 
number usually varies between 25-50 total eosinophils.  The supernatant is stored at - 80C until assayed 
for albumin, eosinophil cationic protein (ECP), histamine, tryptase and lactoferrin. 
 
Levels of human serum albumin (HSA) will be assayed in nasal lavage fluid to evaluate plasma leakage.  
HSA is measured by an enzyme-linked immunosorbent assay (ELISA) sensitive to 1 ng/ml of albumin.  
Levels of histamine and tryptase will also be assayed in nasal lavage fluid to evaluate mast cell activation.  
Histamine is determined using a radioimmunoassay sensitive to 20 ng/ml.  Tryptase is measured by 
fluoroenzyme immunoassay sensitive to 1 ng/ ml.  ECP will be assayed using radioimmunoassay 
sensitivity to 2 µg/ml to indicate eosinophil activation.  An ELISA sensitive to 0.73  ng/ml will measure 
lactoferrin. 
 
We anticipate that in the placebo arm symptoms will increase each day in response to the nasal 
provocation.  Similarly, the levels of histamine, albumin, ECP and lactoferrin, and the number of 
eosinophils will increase on the second and third day of challenge.  The level of tryptase should remain 
constant.  At a minimum, the azelastine hydrochloride in Dymista should reduce symptoms and the levels 
of albumin and lactoferrin on all days of nasal challenge.  The model will also allow us to determine if 
azelastine operates in addition to its role as an antihistamine by reducing mast cell activation.  
Furthermore we will evaluate whether the cellular influx caused by the nasal provocations is reduced 
more by Dymista compared to fluticasone.  We anticipate that fluticasone propionate will have no effect 
on the first day of challenge, but will prevent priming, eosinophil influx, and the increases in level of 
biomarkers associated with priming on subsequent days.  We do not anticipate that 2 days of fluticasone 
will affect mast cell activation.  Lastly, we anticipate, at a minimum, that Dymista will reduce symptoms 
beginning on day 1 of nasal challenge and cellular influx and its consequences on days 2 and 3 of 
challenge. 
 
Stats:  The primary endpoint will be the daily change in albumin levels at visit 1.  To determine the 
sample size, we made some assumptions.  Based on a study of patients receiving 60 mg fexofenadine the 
mean albumin changed from 294 to 64 after treatment.  We assumed azelastine would reduce albumin by 
75% with a standard deviation of 300.  Using a significance level α=0.05, then 20 completed subjects per 
treatment group are needed for at least 80% power to detect a difference from placebo and azelastine 
during the acute reaction.  The same size sample would show a reduction for Dymista on all visits and the 
eosinophil influx compared to placebo.  The sample size is probably insufficient to show a significant 
reduction of eosinophils after Dymista compared to fluticasone, though a trend could be noted. 
 
All statistical analyses will test the null hypothesis of no treatment difference between active treatment 
and placebo versus the alternative hypothesis that there is a difference between treatments.  All statistical 
tests will be two-sided and will be conducted at a significance level of α=0.05. 
 
Secondary efficacy measures include the mean changes from baseline in sneezes, total nasal symptom 
scores, number of eosinophils and the levels of ECP, lactoferrin, tryptase and histamine.   
 
Schedule of event: see attached  
 
Detailed study budget: see attached 
 
We would need a 3 day supply of fluticasone propionate, Dymista and placebo for each of 20 subjects. 
 
References 
 


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Baumgarten CR, Nichols RC, Naclerio RM, Lichtenstein LM, Norman PS, Proud D.  Plasma kallikrein 
during experimentally-induced allergic rhinitis:  Role in kinin formation and contribution to TAME-
esterase activity in nasal secretions.  J Immunol 1986; 137:977-82. 
 
Pipkorn U, Proud D, Lichtenstein LM, Kagey-Sobotka A, Norman PS, Naclerio RM.  Inhibition of 
mediator release in allergic rhinitis by pretreatment with topical glucocorticoids.  New Engl J Med 1987; 
316:1506-10. 
 
Pipkorn U, Proud D, Lichtenstein LM, Schleimer RP, Peters SP, Adkinson NF Jr, Kagey-Sobotka A, 
Norman PS, Naclerio RM.  Effect of short-term systemic glucocorticoid treatment on human nasal 
mediator release after antigen challenge.  J Clin Invest 1987; 80:957-61. 
 
Bascom R, Wachs M, Naclerio RM, Pipkorn U, Galli SJ, Lichtenstein LM.  Basophil influx occurs after 
nasal antigen challenge:  Effects of topical corticosteroid pretreatment.  J Allergy Clin Immunol 1988; 
81:580-9. 
 
Bascom R, Pipkorn U, Lichtenstein LM, Naclerio RM.  The influx of inflammatory cells into nasal 
washings during the late response to antigen challenge:  Effect of systemic steroid pretreatment.  Am Rev 
Respir Dis 1988; 138:406-12. 
 
Bascom R, Pipkorn U, Proud D, Dunnette S, Gleich SJ, Lichtenstein LM, Naclerio RM.  Major basic 
protein and eosinophil-derived neurotoxin concentrations in nasal lavage fluid after antigen challenge:  
Effect of systemic corticosteroids and relationship to eosinophil influx.  J Allergy Clin Immunol 1989; 
84:338-46. 
 
Wachs M, Proud D, Lichtenstein LM, Kagey-Sobotka A, Norman PS, Naclerio RM.  Observations on the 
pathogenesis of nasal priming.  J Allergy Clin Immunol 1989; 84:492-501. 
 
Naclerio RM, Kagey-Sobotka A, Lichtenstein LM, Freidhoff L, Proud D.  Terfenadine, an H1 
antihistamine, inhibits histamine release in vivo in man.  Am Rev Respir Dis 1990; 142:167-71. 
 
Shin M-H, Baroody F, Proud D, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM.  The effect of 
azelastine on the early allergic response.  Clin Exp Allergy 1992; 22:289-95. 
 
Proud D, Bailey GS, Naclerio RM, Reynolds CJ, Cruz AA, Eggleston PA, Lichtenstein LM, Togias AG.  
Tryptase and histamine as markers to evaluate mast cell activation during the responses to nasal challenge 
with allergen, cold, dry air and hyperosmolar solutions.  J Allergy Clin Immunol 1992; 89:1098-1110. 
 
Baroody FM, Cruz AC, Lichtenstein, LM, Kagey-Sobotka A, Proud D, Naclerio RM.  Intranasal 
beclomethasone inhibits antigen-induced nasal hyperresponsiveness to histamine.  J Allergy Clin 
Immunol 1992; 90:373-6. 
 
Majchel AM, Baroody F, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM.  Effect of oxymetazoline on 
the early response to nasal challenge with antigen.  J Allergy Clin Immunol 1993; 92:767-70. 
 
Baroody FM, Rouadi P, Driscoll PV, Bochner BS, Naclerio RM.  Intranasal beclomethasone reduces 
allergen-induced symptoms and superficial mucosal eosinophilia without affecting submucosal 
inflammation.  Am J Resp Crit Care Med 1998; 157:899-906. 
 
Saengpanich S, Assanasen P, deTineo M, Haney L, Naclerio RM, Baroody FM.  Effects of intranasal 
azelastine on the response to nasal allergen challenge.  Laryngoscope 2002; 112:47-52. 


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Allocco FT, Votypka V, deTineo M, Naclerio RM, Baroody FM.  Effects of fexofenadine on the early 
response to nasal allergen challenge.  Ann Allergy Asthma Immunol 2002; 89:578-84. 
 
Baroody FB, Foster KA, Markaryan A, deTineo M, Naclerio RM.  Nasal-ocular reflexes contribute to eye 
symptoms in patients with allergic rhinitis.  Ann Allergy Asthma Immunol 2008100:194-9. 
 
Baroody FM, Shenaq D, DeTineo M, Wang J, Naclerio RM.  Fluticasone furoate nasal spray reduces the 
nasal ocular reflex: A mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.  
J Allergy Clin Immunol 2009; 123:1342-8. 
 
Sivam A, Jeswani S, Rider L, Wang J, DeTineo M, Baroody FM, Naclerio RM, Pinto JM.  Olfactory cleft 
inflammation in present in seasonal allergic rhinitis and is reduced with intranasal steroids.  Am J Rhinol 
Allergy 2010; 24:286-90. 
 

ICF_001.pdf: 
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U of C V08.08.17 
The UNIVERSITY OF CHICAGO 
The Division of the Biological Sciences  The University of Chicago Medical Center 
 
CONSENT/AUTHORIZATION BY SUBJECT FOR PARTICIPATION IN A RESEARCH 
PROTOCOL 
 
Protocol Number: 14-1199 
Name of Subject:   
 
 
 
 
 
 
 
 
 
 
 
Medical History Number:   
 
 
 
 
 
 
STUDY TITLE:  Evaluating factors involved in Dymista’s superior clinical efficacy to fluticasone 
propionate in the treatment of seasonal allergic rhinitis. 
 
Doctors Directing Research: Fuad Baroody, MD, Robert M. Naclerio, MD, Jayant Pinto, MD.   
 
Address:                                              The University of Chicago, 
                                                            Section of OHNS, 
                                                            5841 S. Maryland Ave., MC 1035, 
                                                             Chicago, IL 60637 
 
Telephone Number: 773-702-4790 and 773-702-5889 
 
You are being asked to participate in a research study. A member of the research team will explain what 
is involved in this study and how it will affect you. This consent form describes the study procedures, 
the risks and benefits of participation, as well as how your confidentiality will be maintained. Please 
take your time to ask questions and feel comfortable making a decision whether to participate or not. 
This process is called informed consent.  If you decide to participate in this study, you will be asked to 
sign this form.  
 
WHY IS THIS STUDY BEING DONE? 
The purpose of this study is to investigate how a combination medication, Dymista, achieves its 
effectiveness in controlling the symptoms of seasonal allergic rhinitis (hayfever). 
 
This research is being done because we do not know why this combination medication is more effective 
than its individual components  Both the combination medication Dymista and the individual 
components (Flonase and Astelin) are approved by the FDA and are currently on the market for the 
treatment of hayfever. 
 
You are being asked to be in this study because you are healthy and have seasonal allergies to either 
grass or ragweed, 
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
About 55 people will take part in this study at the University of Chicago. 
 
WHAT IS INVOLVED IN THE STUDY? 
You will undergo a screening evaluation to determine whether you can participate in the full study.  
 
 


Page 2 of 9 
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Screening Visit 
 You will be asked about your allergy history and asked to complete a questionnaire about 
your nasal symptoms. 
 You will be skin tested with common allergens (the stuff that causes hayfever), for 
example, ragweed, grass, cat, dustmites, tree mix, or mold.  A skin test involves 
puncturing your skin with a tiny needle.  If the test is positive, you will develop a red and 
itchy bump around the puncture site within 15 minutes that may last for a day.  Only 
those people who test positive for grass or ragweed will be considered for this study. 
 If you are a woman of childbearing age you will be asked to take a urine pregnancy test.  
Pregnant women will not be allowed to participate in this study. 
 
If you have a history of mild asthma you will be asked to blow into a peak flow meter.  If your FEV1 (a 
measure of lung function) is less than 80% of a predicted normal range for your age and size you will 
not be eligible for the study. 
 
Screening nasal challenge  
If your skin test is positive to grass or ragweed, we will perform a screening nasal challenge test.  
 Before starting the screening challenge test we will spray your nose on both sides with 2 sprays 
of oxymetazoline 0.05% (a nasal decongestant) to prevent it from becoming too stuffy. Being too 
stuffy may interfere with the nasal lavage (wash).  
 We will wash your nose with about 2 teaspoons of a salt solution (nasal lavage) before starting 
the challenges and 10 minutes after each challenge.  
 
The lavages will be saved to test and count the cells associated with allergy.  
 
This screening nasal challenge with antigen (the stuff that causes hayfever) is an experimental procedure 
that involves: 
 On one side of the nose we will spray a diluent (a solution used to dilute the allergen) and then 
either grass or ragweed allergen. We will choose the allergen (grass or ragweed) based on the 
results of your skin prick test. If you are allergic to both we will choose the one you have the 
strongest response to. 
 You will then be asked about your nasal symptoms (sneezing, stuffiness, runny nose and itchy 
nose/throat), and to count the number of sneezes.  
 This nasal test is done once with the substance used to dilute the allergen extract (diluent) and 
then with two increasing doses of either grass or ragweed extract.  This is done over a period of 
about 45 minutes. If you have a history of mild asthma the FEV1 will be repeated after each 
nasal challenge test.   
 
If you have a positive response to the screening nasal challenge test, you will be allowed to have a 2 
week washout period (a time when you do not take a drug or get a nasal challenge).  After that you will 
return to the Nasal Physiology laboratory and receive one of the study drugs and undergo one nasal 
challenge every day for 3 days while still taking study drug.  Another 2 week washout will follow 
followed by another round of treatment (with one of the other study drugs) and 3 nasal challenges on 3 
consecutive days.  Another 2 week washout will follow and the last drug will be given and your nose 
challenged for 3 consecutive days.  Your participation in the study will then conclude. 
 


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All Participants in this study will receive 3 different drugs (A, B, and C as below).  The order in which 
these medications are received will be randomly determined (like the roll of a die). 
 
 Drug A: A steroid nasal spray (fluticasone propionate) approved by the Food and Drug 
Administration (FDA),  
 Drug B: Placebo (spray with no active medicine in it),  
 Drug C:Dymista (a combination of fluticasone propionate and azelastine hydrochloride) also 
approved by the FDA.  
 
This study is double-blinded, meaning that neither you nor the study doctor or his research team will 
know which group you are in until the entire study is finished.  However, this information can be 
obtained if it becomes medically necessary to know which study drug you are taking during the course 
of the study.  
 
 Nasal challenges  
The nasal allergen challenge during the study visits will be performed on 3 consecutive days and will be 
as follows: 
 You will come to the nasal laboratory and allowed to rest for 15 minutes so your nose gets used 
to the environment of the laboratory. 
 You will be asked to fill in a score that reflects the severity of your nasal symptoms of sneezing, 
stuffy nose, runny nose, and itchy nose and we will count the number of sneezes.   
 We will then wash your nose 5 consecutive times with about 2 teaspoons of a salt solution (nasal 
lavage). 
 We will then spray your nose on both sides with 2 sprays of oxymetazoline 0.05% (a nasal 
decongestant) to prevent it from becoming too stuffy, as this may interfere with nasal lavage 
(wash). 
 After a 10 minute wait, you will record sneezes and symptoms again and receive your study drug 
(as mentioned above) in the form of 1 spray in each nostril. 
 After a 10 minute wait, we will apply 2 sprays of the diluent (a solution used to dilute the 
allergen) to your left nostril. 
 After 10 minutes, we will record your sneezes and ask you to fill the score that reflects your 
symptom severity.  We will also perform a nasal lavage. 
 We will then spray your nose with 2 sprays of either grass or ragweed allergen followed 10 
minutes later by a recording of sneezes and symptoms and a nasal lavage. 
 We will then spray your nose with 2 sprays of the same allergen in a higher dose and 10 minutes 
later record sneezes and symptoms and perform a nasal lavage. 
 You will then be discharged from the laboratory and asked to take your study drug in the evening 
and report the following day at approximately the same time with your study drug bottle.  The 
same challenge and study drug will be administered the second day and the third day. 
 After the third challenge, you will stop taking study drug and return to the laboratory 2 weeks 
later so your nose will have rested and returned to baseline. 
 You will undergo consecutive 3 day challenges, except that  another study drug will be used. 
 The same sequence will then happen one last time using the last of the assigned study drug. 
 The study will then be concluded after the third series of study administration and nasal 
challenges. 
 


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 The symptoms you record will allow us to determine how the different drugs are affecting the 
nasal challenge.  We will use the washes to measure cells and substances that your nose releases 
during the allergic reaction.  This will also allow us to determine the effect of the different drugs 
on these substances and cells and help us to understand how these treatments work. 
 
During this study, Dr. Baroody and his research team will collect information about you for the purposes 
of this research. This information will include name, age, date of birth, sex, race, e-mail address, 
telephone number, address and social security number (for payment purposes only), and information 
about your medical history (past medical/surgical history, allergies, medications, family and social 
history and other routine information) and results of pregnancy test, skin test, and nasal challenges.  This 
information will be used to analyze the results of the study and compare groups of subjects.  This 
information will be kept in secure computers and offices of Dr. Baroody and his research staff. 
 
HOW LONG WILL I BE IN THE STUDY? 
We think you will be in the study for about 9 weeks.  
Dr. Baroody may decide to take you off of the study without your consent if: 
 You are unable to meet the requirements of the study; 
 Your medical condition changes; 
 New information becomes available that indicates that participation in this study is not in 
your best interest; or 
 If the study is stopped. 
 
WHAT ARE THE RISKS OF THE STUDY? 
The likely and unlikely risks to subjects participating in this study are listed below:  
 
Fluticasone 
The risks associated with the administration of fluticasone propionate include: 
Likely: 
 sore throat 
 nosebleed 
 Nasal irritation 
 blood in nasal mucus 
 
Less Likely: 
 headache 
 Nasal burning 
 nausea 
 vomiting 
 asthma symptoms and cough 
 
Dymista: 
Likely: 
 a bitter taste 
 
Less Likely: 
 nose bleed 


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 headache 
  sleepiness 
 
Skin testing 
The following side effects are: 
Likely: 
 skin itchiness, irritation 
 
Less likely: 
 
 discomfort 
 
The following side effects below may require prompt treatment with adrenalin or other drugs.  However, 
the risks of these side effects are not very likely and the described reactions are less serious if a person is 
under observation, as you will be in this study, and are readily reversible. 
 
Unlikely: 
 hives 
 flushing 
 low blood pressure 
 
Very unlikely, but serious: 
 asthma requiring treatment with adrenalin or other drugs, 
 anaphylactic shock (a bad reaction to the antigen, the substance that causes allergies, causing 
someone to go into shock, that is to faint and have low blood pressure) 
 
Nasal allergen challenge and nasal lavage 
The antigen placed in your nose may cause sneezing, a runny nose and/or nasal congestion that may last 
up to 24 hours.  Some people may find the reaction very uncomfortable.  Other generalized reactions 
(hives, flushing or asthma) requiring additional treatment with epinephrine may occur. These are not 
serious if a person is under observation and are readily reversible. The nasal lavage may cause some 
mild discomfort at the site of collection.  
 
The following side effects are: 
Likely: 
 sneezing 
 itchy nose 
 runny nose 
 nasal congestion 
 
Less likely: 
 discomfort 
 hives 
 asthma 
 
 
 


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FEV1 measurements 
There are minimal to no risks associated with the tests performed to measure nasal congestion and your 
lung function. 
 
Reproductive risks 
Women: There may be unknown risks to the unborn child if you are pregnant or if you become pregnant 
during the study.  Therefore, you may not enter this study if you are pregnant, or plan to become 
pregnant, or breast-feed an infant during the study period. If you become pregnant during the study, you 
will be taken off study for safety reasons.  If you become pregnant within 28 days after your 
participation in the study, we ask that you contact your study doctor for safety monitoring.  In either 
case, please make your obstetrician aware of your study participation. Your study doctor will ask that 
you, or your obstetrician, provide updates on the progress of your pregnancy and its outcome.  The study 
doctor will make this information available to the study sponsor for safety monitoring follow up. 
 
Men: If you are a male and your spouse or partner thinks she has become pregnant during the study or 
within 28 days after your participation in the study, tell your study doctor immediately.  The study 
doctor will make this information available to the study sponsor for safety monitoring follow-up. 
  
There may be other risks that could arise which are not reasonably foreseeable. If new information 
becomes available which could influence your willingness to continue, this new information will be 
discussed with you. 
 
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY? 
If you agree to take part in this study, there may be little or no direct medical benefit to you. We hope 
the information learned from this study will benefit other individuals with seasonal allergic rhinitis in 
the future.   
 
WHAT OTHER OPTIONS ARE THERE? 
Participation in this study is voluntary. Instead of being in this study you may choose to not participate. 
The decision whether or not you wish to participate in this study will not affect your care at the 
University of Chicago Medical Center. 
 
WHAT ARE THE COSTS? 
Clinical services provided during a clinical trial are either research-related or related to usual medical 
care. Research-related services are done to complete the research and the costs are not the responsibility 
of you or your insurance.  
 
The costs that are considered research-related for this study include the following:  
 Steroid nasal spray (fluticasone propionate) 
 Placebo 
 Dymista 
 All nasal challenges with allergen or diluent 
 All Nasal lavages 
 All labs 
 Skin test 
 Urine pregnancy test 


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 Lung function test 
 Oxymetazoline 0.05% (nasal decongestant) 
 
Usual medical care costs include any and all services that are considered medically necessary for your 
disease. The cost of this usual, ongoing medical care will be the responsibility of you or your insurance, 
and may include deductibles and co-payments. Similarly, this care will be subject to all the same 
requirements and restrictions of your insurance. 
 
If you suffer an unanticipated injury as a direct result of this research and require emergency medical 
treatment, the University of Chicago Medical Center will provide such treatment at the University of 
Chicago Medical Center at no cost to you.  Costs of related non-emergency care for an unanticipated 
research injury will be covered if that care is provided at the University of Chicago Medical Center.  You must 
notify Dr. Baroody as promptly as possible after your injury in order to receive this care.  An injury is 
“unanticipated” if it is not one of the known effects of a study drug, medical device or procedure.  If you 
think that you have suffered a research related injury, you must let Dr. Baroody know right away. 
  
 
WILL I BE PAID FOR MY PARTICIPATION? 
For participation in this study you will receive up to $575. There is no compensation for undergoing the 
skin test. Subjects undergoing the nasal screening challenge will be compensated $25 whether or not 
they are eligible to participate in the study. You will receive $50 for completing each of the 9 
subsequent study visits and $100 as a bonus for completing the study and completion of the final visit. If 
you withdraw from this study early, you will only be compensated for the study visits you completed.  
 
As policies at the University of Chicago require that these payments be given in the form of a check, you 
will need to complete a tax form. Therefore we will be collecting personal information about you 
including your name, address, and social security number.  In addition, because the process for 
requesting a check oftentimes takes several weeks, we will mail your check to you when it is ready.  
Please note that it may take 3-4 weeks after conclusion of your study participation in order for you to 
receive your payment. 
 
WHAT ABOUT CONFIDENTIALITY? 
Study records that identify you will be kept confidential. We will store study information in locked 
offices and/or in computers in Dr. Baroody’s offices and labs that are password protected and have 
limited physical access.  Only Dr. Baroody and his study personnel will have access to the study 
information. 
 
The data collected in this study will be used for the purpose described in the form.  By signing this form, 
you are allowing the research team access to your medical records, which include Protected Health 
Information.  Protected Health Information (PHI) consists of any health information that is collected 
about you, which could include your medical history and new information collected as a result of this 
study.  The research team includes the individuals listed on this consent form and other personnel 
involved in this study at the University of Chicago.  
 
As part of the study, Dr. Baroody and his research team will report the results of your study-related 
procedures and tests explained above to Meda, the company sponsoring the study. The information that 
will be sent will be coded prior to being sent to the sponsor only initials will be use.  This information is 


Page 8 of 9 
U of C V08.08.17 
being sent in order to analyze the results of the study and to determine how the nasal sprays help control 
the symptoms of allergic rhinitis.  This information will be used to analyze the results of the study and 
compare groups of subjects. The study sponsor or their representatives, including monitoring agencies, 
may also review your medical record.  Please note that these individuals may share your health 
information with someone else.   
 
Your name, address, and social security number will be shared with the University of Chicago 
Controller’s Office in order to issue payment. 
 
Your records may be reviewed by federal agencies whose responsibility is to protect human subjects in 
research including the Food and Drug Administration (FDA) and Office of Human Research Protections 
(OHRP).  In addition, representatives of the University of Chicago, including the Institutional Review 
Board (IRB), a committee that oversees the research at the University of Chicago, may also view the 
records of the research to make sure that the study information is correct.  If your research record is 
reviewed by any of these groups, they may also need to review your entire medical record. Because of 
the need to provide information to these parties, absolute confidentiality cannot be guaranteed.  
 
If health information is shared outside the University of Chicago, the same laws that the University of 
Chicago must obey may not protect your health information. 
 
During your participation in this study, you will have access to your medical record. Dr. Baroody is not 
required to release to you research information that is not part of your medical record. 
 
This consent form will be kept by the research team for at least six years. The study results will be kept 
in your research record and be used by the research team for at least six years.  At the time of study 
completion, either the research information not already in your medical record will be destroyed or 
information identifying you will be removed from study results.  Any research information in your 
medical record will be kept indefinitely. 
 
Data from this study may be used in medical publications or presentations.  Your name and other 
identifying information will be removed before this data is used.  If we wish to use identifying 
information in publications, we will ask for your approval at that time. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
Taking part in this study is voluntary.  If you choose not to participate in this study, your care at the 
University of Chicago/University of Chicago Medical Center will not be affected. You may choose not 
to participate at any time during the study.  Leaving the study will not affect your care at the University 
of Chicago/University of Chicago Medical Center. 
 
If you choose to no longer be in the study and you do not want any of your future health information to 
be used, you must inform Dr. Baroody in writing at the address on the first page.  Dr. Baroody may still 
use your information that was collected prior to your written notice.  
We will tell you about significant new information that may affect your willingness to stay in this study.  


Page 9 of 9 
U of C V08.08.17 
 
You will be given a signed copy of this document. This consent form document does not have an 
expiration date. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
You have talked to Dr. Baroody or his research coordinator about this study and you had the opportunity 
to ask questions concerning any and all aspects of the research.  If you have further questions about the 
study, you may call Dr. Baroody at 773-702-4790, or by mail at The University of Chicago, Section of 
OHNS, 5841 S. Maryland Ave., MC 1035,  
Chicago, IL 60637. 
 
If you have a research related injury, you should immediately contact Dr. Baroody at  
773-702-4790 during office hours or you can call the paging service at 773-702-1000 and an OHNS 
resident on call will be paged and call Dr. Baroody as needed. 
 
If you have any questions concerning your rights in this research study you may contact the Institutional 
Review Board, which is concerned with the protection of subjects in research projects.  You may reach the 
Committee office between 8:30 am and 5:00 pm, Monday through Friday, by calling (773) 702-6505 or by 
writing:  Institutional Review Board, University of Chicago, 5841 S Maryland Ave., MC7132, I-625, 
Chicago, Illinois 60637. 
 
CONSENT 
SUBJECT 
The research project and the procedures associated with it have been explained to me.  The experimental 
procedures have been identified and no guarantee has been given about the possible results. I will 
receive a signed copy of this consent form for my records. 
 
I agree to participate in this study.  My participation is voluntary and I do not have to sign this form if I 
do not want to be part of this research study. 
 
Signature of Subject:   
 
 
 
 
 
 
 
Date:    
 
 
Time:    
   AM/PM (Circle) 
 
PERSON OBTAINING CONSENT 
I have explained to  
 
_____________________ 
 the nature and purpose of the study and the 
risks involved.  I have answered and will answer all questions to the best of my ability.  I will give a 
signed copy of the consent form to the subject. 
 
Signature of Person Obtaining Consent:   
 
 
 
 
 
 
Date:    
 
 
Time:    
   AM/PM (Circle) 
 
INVESTIGATOR/PHYSICIAN: 
Signature of Investigator/Physician    
 
 
 
 
Date:    
 
 
Time:    
   AM/PM (Circle)