Conditions: Chronic Rhinosinusitis (Diagnosis) Allergic Rhinosinusitis Chronic Eosinophilic Rhinosinusitis
Keywords: mometasone irrigation chronic rhinosinusitis mometasone spray rhinosinusitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 53
Healthy volunteers: yes

Brief summary:
Chronic rhinosinusitis (CRS) affects up to 12.5% of the US population and has a significant disease burden. The recommended medical management of CRS includes large-volume, low-pressure saline lavage, systemic antibiotics, and intranasal corticosteroids (INCS). While the efficacy and safety of INCS are well-established for the long-term management of CRS, penetration of INCS beyond the nasal vestibule and into the paranasal sinuses is limited. The aim of this study is to evaluate the effectiveness of mometasone furoate large-volume, low-pressure nasal irrigation for surgery-naive CRS patients.

Detailed description:
Mometasone furoate nasal spray (MFNS) is a INCS that is used in the management of CRS. The overall goal of this proposed research project is to optimize topical delivery of MF to the paranasal sinuses in surgery-naive CRS patients through the use of high-volume, low-pressure nasal saline irrigation. The investigators will be conducting a single-site, double-blinded, placebo-controlled randomized clinical trial (RCT) in which we propose to evaluate the effectiveness of MF nasal irrigation compared to MF nasal spray.

Arms:
arm 1: The study intervention will be mometasone furoate powder (1.2 mg/capsule) and placebo nasal spray. The placebo nasal spray will contain the same inert ingredients found in MF nasal spray: glycerin, microcrystalline cellulose and carboxymethylcellulose, sodium citrate, citric acid, benzalkonium chloride, and polysorbate 80. The placebo nasal spray will be packaged identically to the mometasone nasal spray. Participants will be required to dissolve the contents of two capsules into an 8-ounce (240 mL) sinus rinse bottle along with the saline rinse. All participants will be instructed to perform the following once daily: irrigation of both right and left nasal cavity with one-half of the contents of the nasal rinse followed by 2 sprays per nostril of the nasal spray. arm 2: The study intervention will be mometasone nasal spray (50 mcg/spray) and placebo nasal irrigation. The placebo will contain lactose monohydrate and will be supplied in capsules identical to the budesonide capsules. Participants will be required to dissolve the contents of the two capsules into an 8-ounce (240 mL) sinus rinse bottle along with the saline rinse. All participants will be instructed to perform the following once daily: irrigation of both right and left nasal cavity with one-half of the contents of the nasal rinse followed by 2 sprays per nostril of the nasal spray.

Interventions: intervention 1: Mometasone Furoate Nasal Irrigation intervention 2: Mometasone Nasal Spray
Intervention descriptions: intervention 1: Participants will undergo an 8-week treatment course that includes nasal saline irrigation with mometasone powder and placebo nasal spray. intervention 2: Participants will undergo an 8-week treatment course that includes placebo saline irrigation with mometasone nasal spray.

Protocol document:
Prot_SAP_001.pdf: 
                                                                                                                                            Page 1 of 19 
 
 
 
 
 
 
 
 
 
 
Study Protocol and Statistical Plan 
 
 
Project Title: Efficacy of Mometasone Furoate Nasal Irrigation for 
Chronic Rhinosinusitis  
 
NCT03705793 
8/13/2019  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Efficacy of Mometasone Furoate Nasal Irrigation for Chronic Rhinosinusitis  
PIs: Pawina Jiramongkolchai, MD; Jay F. Piccirillo, MD 


                                                                                                                                            Page 2 of 19 
 
Study Team: Pawina Jiramongkolchai, MD; Andrew Peterson, BS; Adam Liebendorfer, BS, 
MA; Jake Lee, MD; Daniel Lander, BS; Sara Kukuljan, BS, RN; Dorina Kallogjeri MD, MPH  
Sponsor: Department of Otolaryngology-Head and Neck Surgery, Washington University in St. 
Louis School of Medicine 
 
Abstract 
Chronic rhinosinusitis (CRS),inflammation of the paranasal sinuses and lining of the nasal cavity 
for 12 weeks or more, affects up to the 12.5% of the US population and has a significant 
disease burden. Patients with CRS visit primary care physicians twice as often as those without 
the disease and have five times as many prescriptions filled. Based on national ambulatory 
data, rhinosinusitis accounts for more outpatient antibiotic prescriptions than any other 
diagnosis. The annual total direct and indirect cost of CRS exceeds $12 billion dollars.  
 
Because of the chronic nature of the disease, medical therapy for CRS is focused on 
symptomatic management. Current first-line therapies include large-volume, low-pressure nasal 
saline irrigation, intranasal corticosteroids, and systemic antibiotics.  
Nasal sinus saline irrigation is a widely recommended therapy for CRS. Several studies have 
demonstrated that large-volume, low-pressure nasal saline irrigation can improve distribution of 
pharmacologic therapeutics throughout the nasal cavity and sinuses, and enhance removal of 
mucus and bacteria/biofilms. As a result of the low-cost, excellent safety profile, and high patient 
compliance, nasal saline irrigation is an appealing long-term topical therapy for CRS.   
 
While the efficacy and safety of intranasal corticosteroids (INCS), such as budesonide, are well-
established for the long-term management of CRS, penetration of INCS into the paranasal 
sinuses is limited. A recent clinical trial led by Dr. Piccirillo and colleagues at Washington 
University demonstrated that the addition of budesonide capsules to daily large-volume, low-
pressure sinus saline irrigation for one month resulted in clinically meaningful improvement in 
self-reported functional status and quality of life measures as well as objective measurements of 
CRS. Like budesonide, mometasone furoate (MF) is a second-generation INC. Mometasone is 
currently used as an inhalational drug for the treatment of asthma, allergic rhinitis, and nasal 
polyps. Due to its increased lipophilicity and extensive hepatic metabolism, however, 
mometasone has a markedly reduced systemic availability as compared to budesonide. In a 
recent double-blinded, placebo-controlled randomized clinical trial (RCT), Harvey et al 
demonstrated that MF nasal irrigation was superior to MF nasal spray in the management of 
CRS symptoms following sinus surgery, as measured by patient-reported outcomes and 
endoscopic findings. 
 
The goal of this research project is to explore the impact of the addition of mometasone to high-
volume, low-pressure nasal sinus saline irrigation (aka “Neti-Pot”-type systems) for surgery-
naïve patients with CRS without nasal polyps. The overall objective of this study is to optimize 
medical management of CRS symptoms prior to escalation of surgery, and to evaluate a 
clinically meaningful question of whether steroid nasal irrigation is superior to steroid spray with 
saline nasal irrigation alone.   
 
 
The specific aims of this study are as follows: 
1. Compare the effectiveness of MF nasal irrigation to that of MF nasal spray in the 
management of CRS symptoms in surgery-naïve patients. 
2. Evaluate the effect of MF nasal saline irrigation on the HPA axis compared to that of MF 
nasal spray.  


                                                                                                                                            Page 3 of 19 
 
 
To answer the research questions, the study design will be a double-blinded, randomized 
clinical trial. Up to 50 adult patients with complaints of purulent nasal drainage accompanied by 
nasal obstruction, facial pain-pressure-fullness, or both and reduction or loss of smell for 12 
weeks or greater will be eligible. The intervention will be 8 weeks of either 1) mometasone nasal 
saline irrigation and placebo nasal spray or 2) mometasone nasal spray and nasal saline 
irrigation.  The primary outcome measure will be the average per-patient change in SNOT-22 
between the two treatment groups.


                                                                                                                                            Page 4 of 19 
 
SYNOPSIS 
Study Title 
Effectiveness of Mometasone nasal irrigation for chronic rhinosinusitis. 
Objective 
The primary objective of this proposed project is to evaluate the effectiveness of 
MF nasal saline irrigation as compared to the commonly used MF nasal spray in 
the medical management of CRS symptoms in patients who have not 
undergone sinus surgery. 
 
Study Period 
Planned enrollment duration for each subject: 8 weeks  
Planned study duration: I year  
Number of 
Patients 
Up to 50 adult patients with complaints of purulent (not clear) nasal drainage 
accompanied by nasal obstruction, facial pain-pressure-fullness, or both and 
reduction or loss of smell for 12 weeks or greater. 
Study Drug 
Mometasone in the form of a nasal irrigation or nasal spray.  Mometasone is an 
anti-inflammatory glucocorticoid steroid that is used for the treatment of asthma, 
allergic rhinitis, and nasal polyps 
Study Design 
Prospective  randomized clinical trial 
Inclusion and 
Exclusion 
Criteria 
Inclusion Criteria: 
Adults 18-70 years of age 
12 weeks or longer of two or more of the following signs and symptom 
consistent with chronic rhinosinusitis (CRS)1, 2: 
mucopurulent drainage (anterior, posterior, or both), nasal obstruction 
(congestion), facial pain-pressure-fullness, and decreased sense of smell 
AND inflammation documented by one or more of the following findings: 
purulent (not clear) mucus or edema in the middle meatus or ethmoid region, 
radiographic imaging showing inflammation of the paranasal sinuses 
 
Exclusion criteria: 
Unable to speak English 
Polyps in nasal cavity or the middle meatus 
History of comorbid ciliary dyskinesia, cystic fibrosis or any other mucociliary 
condition 
Dependence on prolonged corticosteroid therapy for comorbid conditions, such 
as asthma and chronic obstructive pulmonary disease. 
History of oral or systematic antibiotic use in the past 2 weeks 
History of sinus surgery  
History of cerebrospinal fluid leak 
History of allergy to mometasone or other topical steroids 
Pregnant or breast feeding 
Current infection or history of one of the following infections: Tuberculosis (TB) 
lung infection, or Herpes infection of the eye. 
Baseline SNOT-22 total scores below 9 were excluded due to the inability to 
achieve a minimally clinically improved difference 
Known history of bleeding disorder, topical or injectable lidocaine allergy, use of 
blood thinners 
Primary 
Outcome 
The change in the SNOT-22 (©2006, Washington University, St. Louis, MO) 
score between baseline and eight-week intervention and calculated as: ∆SNOT-
22 = SNOT-22baseline — SNOT-228-week follow-up. 
Measurements SNOT-22; ACE-27 Comorbidity Index; Lund Kennedy Endoscopy Grading Scale 
Lund – MacKay CT score (not required); Global Clinical Impression Scale; 


                                                                                                                                            Page 5 of 19 
 
Olfactory Dysfunction Outcomes Rating (ODOR) 
Statistical 
Methodology 
Within subject change in SNOT-22 between intervention groups.  
 
I. Statement of the Research Problem  
 
Definition and Burden of Rhinosinusitis 
Chronic rhinosinusitis (CRS) is the inflammation of the paranasal sinuses and lining of the nasal 
cavity for 12 weeks or more and is characterized by symptoms of facial pain-pressure-fullness, 
nasal discharge, and nasal obstruction.1 1 in 8 adults are affected and over 30 million cases are 
diagnosed each year.2,3  Analysis of national ambulatory data demonstrates that rhinosinusitis 
accounts for more outpatient antibiotic prescriptions than any other diagnosis.4 Patients with 
CRS visit primary care clinicians twice as often as those without the disorder and have 5 times 
as many prescriptions filled.5 Approximately $8.3 billion is spent annually on CRS, primarily on 
prescription drugs and office-based care.6 Surgery for CRS, which costs on average $7,700 per 
patient, is performed nearly 250,000 times per year in the United States.7 
 
CRS is primarily an inflammatory disease, with exacerbations often associated with concomitant 
infection. However, treating the episodic infections alone leaves the underlying condition 
untreated, likely contributing to an increased frequency of exacerbations. In this way, CRS is 
very similar to chronic bronchitis. CRS is associated with sinus edema and impaired mucociliary 
clearance. With edema-related obstruction and retained mucus, bacterial infection can more 
easily occur.1 
 
Medical Management 
The medical management of CRS includes antibiotics, topical nasal steroid sprays, and saline 
irrigation. Antibiotics are often prescribed for CRS and national surveys suggest a large degree 
of over utilization with development of serious adverse side-effects and resistant organisms.8-20 
 
Nasal Sinus Irrigation 
Nasal sinus saline irrigation (aka Neti-Pot) is widely recommended and is a common treatment 
for CRS. The use of either isotonic ("normal" saline) or hypertonic saline is recommended, 
andthere have been over 12 studies examining the impact of saline irrigation in the 
management of CRS.  A recent systematic review by Thomas et al. 17 analyzed the best 
mechanism to distribute topical therapeutics to the sinuses in CRS patients. Large-volume, low-
pressure irrigation devices resulted in better distribution to the nasal cavity and sinuses, 
especially after surgery, than low-volume devices. In addition, large-volume devices were found 
to overcome any adverse effects of head position or nasal cavity anatomy on sinus distribution. 
Due to its low cost, high patient acceptance, and high benefit-to-risk margin, large-volume, low-
pressure saline sinus irrigation is a widely recommended treatment for CRS. 7,11,14,15,17   
 
Topical Nasal Steroid Spray 
Intranasal corticosteroid sprays (INCS) are established as safe and effective monotherapy or 
adjuvant treatments for CRS. 21,22 A Cochrane Review in 201122 examined the efficacy of topical 
steroids for CRS without polyps in five clinical trials. When compared to placebo, topical steroid 
improved symptom scores (standardised mean difference -0.37; 95% CI (-0.60 to -0.13), P = 
0.002; five trials, n = 286) and had a greater proportion of responders (risk ratio 1.69; 95% CI 
(1.21 to 2.37), P = 0.002; four trials, n = 263). While the use of INCS is generally recommended 
in the setting of CRS, there is limited penetration of the steroid beyond the nasal cavity and into 


                                                                                                                                            Page 6 of 19 
 
the paranasal sinuses. 23,24  Therefore, there has been great interest in the use of novel delivery 
approaches and devices to improve intra-sinus corticosteroid deposition.25 
 
Non-Standard Delivery of Topical Steroids 
Three studies have examined the use of topical steroids delivered through low-pressure, high-
volume saline irrigation.  Snidvongs et al.22 examined a large cohort of patients with CRS 
(n=111), 49 of whom had a diagnosis of CRS without nasal polyps.  Treatment was with once 
daily nasal irrigations of 1mg budesonide/betamethasone in 240 mL of normal saline in the 
immediate post-operative period. Significant improvements were seen in SNOT-20 scores (2.3 ± 
1.1 vs 1.2  ± 0.9), symptom scores (2.5  ± 1.1 vs 1.4  ± 1.0) and Lund-Kennedy endoscopy 
scores (4.3  ± 2.0 vs 1.9  ± 1.6). No adverse outcomes were reported. An open-label 
prospective study (n=9) by Dr. Piccirillo and colleagues at Washington University26 evaluated 
the efficacy of once daily irrigation with budesonide (0.25 mg). Subjects also underwent adrenal 
function assessment with the cosyntropin test before and after budesonide therapy. All subjects 
showed appropriate adrenal response to cosyntropin stimulation before and after the 
budesonide trial, and the mean change in SNOT-20 scores before and after budesonide therapy 
was statistically and clinically significant. Steinke27 conducted a prospective pilot study in 8 
subjects with allergy, as defined by a positive skin prick test; 4 subjects were classified as 
having aspirin-exacerbated respiratory disease, and all but 1 had physician-diagnosed asthma. 
The subjects received a 3-month course of twice daily budesonide irrigations (500 μg into >100 
ml saline). The median sinus CT score before treatment was 15 (maximum=30), which 
improved to 5 (p < .05) after treatment. After budesonide treatment, subjects’ sinus scores 
decreased (mean ± SD) from 43.1 ± 5.4 to 20.1 ±3.0 (P<.02). In addition, subjects reported a 
significant improvement in sense of smell.  Of the four patients with nasal polyps, three had 
complete resolution.  The authors concluded that their study supports the concept that addition 
of budesonide inhalation suspension to standard nasal saline irrigation produces subjective and 
objective benefit in eosinophilic sinus disease. Furthermore, in a recently completed double-
blinded, placebo-controlled, randomized clinical trial by Piccirillo et al at Washington University 
(submitted), the addition of 1 mg of budesonide to daily large-volume, low-pressure sinus saline 
irrigation for one month resulted in clinically meaningful improvements in self-reported functional 
status and quality of life measures as well as objective measurements of chronic rhinosinusitis. 
Although the study included both patients with and without nasal polyps, patients with nasal 
polyps received only a minor benefit from budesonide. Patients with nasal polyps may have 
reduced topical application and penetration of budesonide as well as endotypes that are less 
responsive to the anti-inflammatory effects of glucocorticosteroids.  
 
Like budesonide, mometasone furoate is a second-generation INC. The newest of the INCS, 
mometasone is currently used as an inhalational drug for the treatment of asthma, allergic 
rhinitis, and nasal polyps. Due to its increased lipophilicity and extensive hepatic metabolism, 
however, mometasone has a markedly reduced systemic availability as compared to 
budesonide (<0.1% versus 34%, respectively).28 Furthermore, using various pharmacologic 
tests, including competition and McKenzie assays, mometasone has been shown to have higher 
potency than budesonide.28 While corticosteroids can suppress the HPA axis, multiple studies 
have demonstrated that INCS have no significant impact on the HPA axis. In 6 randomized 
controlled parallel-group or placebo trials in adults and children, no evidence of HPA axis 
suppression was seen. 29  
 
In a recent double-blinded, placebo-controlled randomized clinical trial (RCT), Harvey et al 
demonstrated that MF nasal irrigation was superior to MF nasal spray in the management of 
CRS symptoms following sinus surgery, as measured by patient-reported outcomes and 


                                                                                                                                            Page 7 of 19 
 
endoscopic findings.23 In the study, participants were assigned to either mometasone capsules 
(2 mg daily) or placebo intervention for 12 months following sinus surgery. The MF nasal 
irrigation group had a significantly greater improvement in nasal blockage visual analog 
symptoms compared to that of the MF nasal spray group (p=0.029). Furthermore, on 
endoscopic examination, the MF nasal irrigation group had significantly greater disease 
suppression than the MF nasal spray group, as evidenced by lower modified Lund-Kennedy 
endoscopic scores (p=0.018). Harvey et al reported no adverse effects from their dosage of 
mometasone. 
 
Due to mometasone’s favorable pharmacologic properties, we propose to evaluate the 
effectiveness of the addition of mometasone to large-volume, low-pressure sinus saline 
irrigation for patients with CRS without polyps in a single-site randomized clinical trial. We 
hypothesize that the addition of MF to a large-volume, low-pressure sinus saline irrigation will 
result in clinically meaningful benefits for patients with CRS as measured by subjective and 
objective outcome measures. We anticipate that MF dispensed in a large volume, low-pressure 
device will be superior to that of MF nasal spray combined with nasal saline irrigation in the 
medical management of CRS in surgery-naïve, non-polyp patients. 
 
II. Specific Aims  
The primary objective of this proposed project is to evaluate the effectiveness of MF nasal 
saline irrigation as compared to the commonly used MF nasal spray in the medical management 
of CRS symptoms in patients who have not undergone sinus surgery. 
Specifically, we propose:  
 
1. Compare the effectiveness of MF nasal irrigation to that of MF nasal spray in the 
management of CRS symptoms in surgery-naïve, non-polyp patients.  
 
Participants will be randomized to either 1) 8-weeks of MF nasal saline irrigation and placebo 
nasal spray or 2) MF nasal spray and nasal saline irrigation. The primary outcome measure will 
be the within subject changes in SNOT-22 scores pre-and post-treatment. We hypothesize that 
MF nasal saline irrigation, when compared to that of MF nasal spray alone, will be more 
effective in the treatment of CRS symptoms.  
2. Evaluate the effect of MF nasal saline irrigation on the HPA axis compared to MF nasal 
spray10 participants will be sampled from each study arm in order to ascertain the effect of 
mometasone nasal irrigation on the function of the hypothalamus-adrenal-pituitary (HPA) axis, 
as measured by the cosyntropin test before and after completion of intervention. In prior studies 
on the safety of MF nasal spray in children and adults, no discernible effects of MF nasal spray 
on the function of the HPA axis were reported.29 To our knowledge, a study examining the 
impact of MF nasal saline irrigation on the HPA axis has not been performed. Based on prior 
studies demonstrating the safety of MF nasal spray, we hypothesize that MF nasal saline 
irrigation will have a negligible effect on the HPA axis. Furthermore, subjects will be queried 
throughout their participation in the study regarding any adverse events experienced with 
mometasone.  
 
III. Experimental Plan, Methods, and Data Analysis  
 
Study Design: Randomized clinical trial 
Subjects: Up to 50 adult patients with complaints of purulent nasal drainage accompanied by 
nasal obstruction, facial pain-pressure-fullness, or both and reduction or loss of smell for 12 
weeks or greater. 


                                                                                                                                            Page 8 of 19 
 
Inclusion Criteria: 
Adults 18-70 years of age 
Twelve (12) weeks or longer of two or more of the following signs and symptom consistent with 
chronic rhinosinusitis (CRS)30,31. 
mucopurulent drainage (anterior, posterior, or both), nasal obstruction (congestion),facial pain-
pressure-fullness, and decreased sense of smell 
AND inflammation documented by one or more of the following findings: 
purulent (not clear) mucus or edema in the middle meatus or ethmoid region, and/or 
radiographic imaging showing inflammation of the paranasal sinuses 
 
Exclusion criteria: 
Unable to speak English 
Current nasal polyps  
Previous sinus surgery 
History of comorbid ciliary dyskinesia, cystic fibrosis or any other mucociliary condition 
Dependence on prolonged corticosteroid therapy for comorbid condition, such as asthma and 
chronic obstructive pulmonary disease. 
History of oral or systematic antibiotic use in the past 2 weeks 
 
History of cerebrospinal fluid leak 
History of allergy to mometasone or other topical steroids 
Pregnant or breast feeding 
Current infection or history of one of the following infections: Tuberculosis (TB) lung infection, or 
Herpes infection of the eye. 
Baseline SNOT-22 total scores below 9 are excluded due to the inability to achieve a minimally 
clinically improved difference 
 
Variables of Interest: 
Demographic - age, gender, and race. 
Index condition – Duration of CRS symptoms, response to previous treatments 
Co-morbid conditions - Presence and severity of general comorbid conditions will be assessed 
with ACE-2732. Presence of rhinosinusitis-specific comorbidities will include: inhalant allergies, 
asthma, and aspirin sensitivity. 
 
Randomization 
 
Using a randomization scheme with permuted blocks of varying sizes, participants will 
be randomized to receive 8 weeks of either 1) MF nasal saline irrigation (2.4 mg) and placebo 
nasal spray or 2) MF nasal spray (50 mcg/spray) and nasal saline irrigation.   
Intervention 
 
MF nasal spray is currently dosed at 2 sprays/nostril for a total amount delivered of 200 
mcg. When a patient administers a nasal spray, approximately 70% of the dose is cleared from 
the nose into the throat and swallowed. The remaining 30% remains deposited in the nose. 
Therefore, if a patient receives 200 mcg of mometasone nasal spray, only 60 mcg of this dose 
remains in the nasal cavity. 28 Personal communication with Advanced Rx and review of the 
literature regarding fluid/topical nasal residuals suggests that a total of 2.4 mg of MF powder 
reconstituted in 240 mL of nasal saline is an equivalent dose to that of the metered spray.  
 
Calculations  
Steroid nasal spray  
200 mcg dose of steroid nasal spray, 30% of the dose is retained in the nasal cavity  


                                                                                                                                            Page 9 of 19 
 
200 mcg x 0.30= 60 mcg in the nasal cavity  
 
Steroid Nasal Irrigation  
Mometasone 2.4 mg dissolved in 240 mL of saline  
2.5% of the dose remains in the nasal cavity following irrigation  
2.4 mg x 0.025= 0.06 mg or 60 mcg  
 
Harvey et al recently completed a study evaluated the effectiveness of mometasone nasal 
irrigation dosed at 2 mg daily for management of CRS symptoms following sinus surgery with no 
adverse effects reported during the study’s yearlong duration.30 
 
Participants will be provided with a 2-month supply of either 1) MF nasal spray and nasal saline 
irrigation or 2) MF nasal irrigation and placebo nasal spray.  
 
All participants will be provided with an 8-ounce (240 ml) NeilMed Sinus Rinse Regular Bottle 
Kit and a two-month supply of USP Grade Sodium Chloride & Sodium Bicarbonate Mixture (pH 
balanced, Isotonic & Preservative & Iodine Free) commercially prepared packets. Subjects may 
substitute the NeilMed Sinus Rinse Regular Bottle Kit for a nasal irrigation system, which in the 
opinion of the Principal Investigator, is similar to the NeilMed system and embodies the low-
pressure, high-volume concept of nasal irrigation.  Examples of such systems include, but are 
not limited to, ceramic or plastic neti pot or nasal douch (Nasendusche). Subjects will need to 
purchase distilled water or boil tap water for five minutes for use with the saline irrigation. 
Subjects will be required to dissolve the contents of two capsules (either mometasone or lactose 
placebo) into the 8-ounce (240 ml) NeilMed Sinus Rinse Regular Bottle along with the saline 
rinse. All subjects will be instructed to irrigate both right and left nasal cavity with one-half of the 
contents of the nasal rinse once daily. The subjects will receive written instructions and a video 
prior to initiation of the intervention to ensure proper delivery.   
 
For participants randomized to MF nasal spray, they will be instructed to perform the following 
once daily: nasal saline irrigation with lactose placebo capsules as outlined above immediately 
followed by 2 sprays per nostril of MF nasal spray. For participants receiving MF nasal irrigation, 
they will be instructed to perform the following once daily: nasal saline irrigation with 
mometasone capsules as outlined above immediately followed by 2 sprays per nostril of the 
placebo spray.  
 
Each study bottle (Mometasone capsule, placebo capsule, mometasone nasal spray, placebo 
nasal spray) will be assigned with a number from 1-50. Only Dr. Kallogjeri will have a list that 
links the treatment type (Mometasone nasal irrigation arm versus mometasone nasal spray arm) 
with the bottle number. The subject and the rest of the study team will remain blinded to the 
randomization assignment. Dr. Kallogjeri is the biostatistician of the study and otherwise is not 
involved with the participants. 
 
In the event of a Serious Adverse Event determined by the PI to necessitate the breaking of the 
blind, the intervention assignment will be revealed by Dr. Kallogjeri to the medical staff doctor 
caring for the patient. In the event Dr. Kallogjeri is unable to be reached in a time needed, to 
assure the safety of the subject, the blind can be broken by Sara Kukuljan, RN, or Drs. Piccirillo 
or Jiramongkolchai and information will be shared with the medical staff assuming care for the 
patient.  
 


                                                                                                                                            Page 10 of 19 
 
The mometasone capsules and mometasone spray will be prepared by Advanced Rx  
Pharmacy, Plymouth Meeting, Pennsylvania.   
 
Advanced Rx will provide the mometasone capsules and placebo capsules free of charge. The 
cost of a 30 day supply of mometasone nasal spray will be $79/study participant. Likewise, the 
cost of a 30 day supply of placebo nasal spray will be $79/study participant. Therefore, the cost 
for the active mometasone spray + placebo nasal irrigation will be $158/study participant and 
the cost for the placebo nasal spray + mometasone nasal irrigation will be $158/study 
participant.  
 
A randomized list will be provided to Advanced Rx and the medications mailed directly by 
Advanced Rx to the study participants.  
 
Mometasone Nasal Irrigation 
Mometasone is an anti-inflammatory glucocorticoid steroid that is used for a variety of common 
ailments. Among conditions related to the respiratory tract, mometasone is used as an 
inhalational drug for the treatment of asthma, allergic rhinitis, and nasal polyps. The mechanism 
of action of mometasone is similar to other corticosteroids and includes a wide range of 
inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, 
macrophages and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and 
cytokines) involved in allergic- and non-allergic-mediated inflammation.28  
 
Subjects randomized to the mometasone nasal irrigation intervention arm will be required to mix 
2.4 mg of mometasone into the sinus rinse bottle and rinse each nasal cavity with one half of 
the bottle (~ 4 ounces or ~120 ml) daily.  The inert ingredients are: loxasperse powder, which 
increases solubility and dispersibility of mometasone and is microbiologically safe; mannitol, 
which is widely used in pharmaceutical products as a capsule diluent; and Xylifos™ powder, 
which is a proprietary powder excipient used safely in pharmaceutical compounding for nasal 
nebulization or nasal irrigation. 
 
Placebo Nasal Spray  
 
The placebo nasal spray will be packaged in the same bottle as that of MF nasal spray. 
The nasal spray will prepared by Advanced Rx Pharmacy and will contain the same inert 
ingredients found in MF nasal spray: glycerin, microcystralline cellulose and 
carboxymethylcellulose sodium, sodium citrate, citric acid, benzalkonium chloride, and 
polysorbate 80. Subjects in the mometasone nasal irrigation arm will be instructed to first irrigate 
with mometasone followed by use of the placebo nasal spray.  
 
Mometasone Nasal Spray  
 
 
Subjects randomized to the mometasone spray intervention arm will receive a 2 month 
supply of MF nasal spray (50 mcg/spray), which is commercially available as NasonexTM, but 
will be prepared for the study by Advanced Rx Pharmacy. Participants will be instructed to use 2 
sprays per nostril once a day followed by nasal saline irrigation 
 
Placebo Nasal Irrigation 
 


                                                                                                                                            Page 11 of 19 
 
The placebo product will contain lactose monohydrate and will be supplied in clear 
plastic capsules, which are identical to the budesonide capsules.  The capsules will only contain 
lactose as there are no other ingredients. 
 
Cosyntropin Test  
Measuring blood levels of cortisol after cosyntropin stimulation is the gold standard to evaluate 
effects of exogenous corticosteroids on the HPA axis. The effects of mometasone nasal spray 
on the hypothalamus-pithuitary-adrenal (HPA) axis have been evaluated in 6 clinical trials in 
both adults and children (dose range 100 ug once daily to 400 ug twice daily). In all 6 trials, no 
effects of mometasone nasal spray on the HPA axis was discernible.29 To our knowledge, a 
similar demonstration of the safety of a nasally administered mometasone wash has not been 
performed. As a result, ten participants from each study arm will be selected for an optional 
cosyntropin test to assess the effect of mometasone nasal irrigation on the HPA axis.  
 
Baseline levels of serum cortisol will be measured at the subject’s first visit. Subjects will then 
receive 0.25 mg of cosyntropin and 10 mg of mannitol reconstituted with 1 mL of 0.9% sodium 
chloride as an intramuscular injection to stimulate the adrenal cortex. Serum will be drawn 30 
minutes and cortisol level measured. This test will be repeated upon the completion of 60 days 
of mometasone nasal irrigation or spray. If mometasone is absorbed systematically via nasal 
irrigation, serum cortisol should be inappropriately low upon cosyntropin stimulation compared 
to baseline. No change in serum cortisol is expected in the mometasone nasal spray group 
based on prior studies.  The cosyntropin test will be performed at the Center for Outpatient 
Health and blood cortisol levels measured by the General Clinical Research Center 
Immunoassay Core Laboratory.  
 
In the event that at the first pre-intervention cosyntropin visit, a post-stimulation level is below 
the critical level of 18 µg/dL, indicating an insufficient adrenal response, the PI will be notified 
and the study participant contacted. With an abnormal cortisol level pre-intervention, the study 
participant will not be eligible for further participation in the study and the study coordinator will 
recommend that the participant be evaluated by his/her primary care physician.  
  
In the event that a post-stimulation level is below the critical level of 18 µg/dL indicating an 
insufficient adrenal response, the PI will be notified and the study coordinator will notify the 
patient and recommend a referral to the study participant’s primary care physician. Study 
participants in either intervention arm will remain on the intervention until cosyntropin lab values 
are received and reviewed.  
 
Because certain medical conditions and medications can affect the cosyntropin test and result in 
spurious results, subjects will also be excluded from the test if they met any one of the following 
criteria: concurrent or recent use (within the past 30 days) of systemic corticosteroids; history of 
pituitary disease; morbid obesity  as measured by body mass index; concurrent or recent use of 
medications that accelerate the clearance of cortisol, such as dilantin, rifampin, amphetamines, 
or lithium carbonate; concurrent use of medications that interfere with the production of cortisol, 
such as ketoconazole, amphotericin B, bupropion, Echinacea, fluoroquinolones, itraconazole, 
licorice, and ma huang (Ephedra); use of oral contraception; use of female or male hormone 
therapy; a radioactive scan performed within 7 days before the test; known hypersensitivity to 
cortisol, corticotropin, or cosyntropin; allergic disease associated with anaphylactic reactions or 
breathing difficulties; or pregnancy. 


                                                                                                                                            Page 12 of 19 
 
 
Exemption From IND Requirements 
The use of mometasone in a nasal saline rinse is a change in the approved route of 
administration. An exemption from IND requirements will be requested as the proposed use of 
mometasone in this study fulfills all of the criteria for exemption: 
 
 
1. Mometasone is lawfully marketed in the United States. 
 
2.  This study is not intended to be reported to the FDA in support of a new indication or  
significant change in labeling. 
 
3. This study is not intended to support a significant change in the advertising for the  
drug. 
 
4. The study does not involve a route of administration, dose, patient population, or other  
factor that significantly increases the risk (or decreases the acceptability of the risk)  
associated with the use of mometasone. 
5. The study will be conducted in compliance with the requirements for review by an IRB  
(21 CF R part 56) and with the requirements for informed consent (21 CFR part 50). 
 
6. The study is not intended to promote or commercialize mometasone. 
 
 
Concomitant Medications 
At the time of enrollment, subjects may already be using a topical nasal steroid medication (ie., 
fluticasone or Flonase®) or nasal irrigation.  Participants who have been previously using a 
nasal spray or nasal irrigation will be asked to discontinue use while enrolled in the study.  
 
Patient-reported Outcome Measure 
The SNOT-22 (©2006, Washington University, St. Louis, MO) will be used to capture the 
physical, functional, and emotional consequences of rhinosinusitis.  The SNOT-22 is a 
validated, patient-reported outcome measure applicable to chronic sinonasal conditions.33 The 
severity of 22 rhinosinusitis-related symptoms and physical signs are measured using a Likert 
scale as follows: 0= “No problem”; 1=”Very mild problem”; 2=”Mild or slight problem”; 
3=”Moderate problem”; 4=”Severe problem”; and 5=”Problem as bad as it can be”. Higher total 
scores on the SNOT-22 suggest worse patient functioning or symptom severity (score range: 0-
110). A minimally clinically improved difference (MCID) in symptoms that is perceptible and 
pertinent to the individual patient on the SNOT-22 has been previously described as an 
improvement of at least 9 points.33,34   
 
Primary Outcome Measure 
Study participants will be asked to complete the SNOT-22 at baseline, two weeks, four weeks, 
six weeks, and eight weeks following start of medications. The SNOT-22 score will be 
calculated as the average per item score for each of the 22 items and the value will range 
between 0 and 5.  For subjects who answer less than 22 items (i.e., don’t completely answer the 
SNOT-22), the total score will be the average per item value for the items that were answered. 
The change in SNOT-22 scores between baseline and eight weeks will serve as the primary 
outcome measure in this study and will be calculated as: 
 
Primary Outcome Measure, ∆SNOT-22 = SNOT-22baseline — SNOT-228-week follow-up. 
To assess the trajectory of change within subjects randomized to the two treatment arms the 
baseline, two-week, four-week, six-week, and eight-week SNOT-22 assessment will be 
compared.  
 
Secondary Outcome Measure. 


                                                                                                                                            Page 13 of 19 
 
University of Pennsylvania Smell Identification Test (UPSIT):  
The UPSIT is a test of olfactory identification and consists of four 10-page booklets, with a total 
of 40 items. On each page, there is a different “scratch and sniff” strip and four choice options. 
Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, 
and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that 
identifies the normalcy benchmark based on age and gender. The UPSIT is commercially 
available, takes 10-15 minutes to complete, and is the gold standard test to assess smell 
identification. Subjects will complete the UPSIT at their baseline and final visit.  
 
Clinical Global Impression Scale (CGI):  
The overall response to treatment will be measured with a modification of the Clinical Global 
Impression (CGI) scale. 32,35  Upon completion of the study, subjects will be asked to answer the 
following question: "Overall, how would you rate your response to treatment?"  Response 
options are: 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No 
Change, 5 = Minimally Worse, 6 = Much Worse, 7 = Very Much Worse. 
In addition, subjects will be asked to rate their subjective sense of smell pre- and post-
intervention.  
 
Questionnaire for Olfactory Dysfunction (QOD):  
The QOD is a validated quality of life questionnaire for patients with olfactory disorders. 
Subjects will complete the QOD at their baseline and final visit.  
 
Olfactory Dysfunction Outcomes Rating (ODOR): 
The ODOR is a quality of life measure capturing physical, functional, and emotional limitations 
specific to smell loss. It is currently undergoing validation and is designed to be more concise, 
readable, and comprehensive than the QOD. Subjects will complete the ODOR questionnaire at 
their baseline and final visit. 
 
Physical Examination including nasal endoscopy performed for clinical purposes The physical 
examinations will be done as part of routine care during the patients’ scheduled clinic visit.  The 
findings from the endoscopic examination will be collected for research purposes and will be 
recorded using the grading system proposed by Lund and Kennedy.36  
 
Endoscopic Findings  
 
None Present  
Present  
1. Crusting 
0 
1 
2. Erythema  
0 
1 
3. Swelling  
0 
1 
4. Scar Band  
0 
1 
5. Purulent Drainage 
0 
1 
6. Thick Mucous  
0 
1 
 
None Present  
Present in middle 
meatus  
Present outside 
middle meatus  
7. Polyps  
0 
1 
2 
  
 
 
Radiologic Examination 
Radiologic examination, including CT scan of the sinuses, will not be required for enrollment in 
the study.  Enrolled subjects who receive a CT scan of the sinuses for clinical reasons during 
the period of this study will have the results of the radiologic examination collected for research 


                                                                                                                                            Page 14 of 19 
 
purposes and will be recorded according to the Lund MacKay system and possibly included in 
the data analysis.36,37  
Sinus system  
Left  
Right  
Maxillary  
 
 
Anterior ethmoid 
 
 
Posterior ethmoid 
 
 
Sphenoid 
 
 
Frontal  
 
 
Ostiomeatal complex  
 
 
*Scores 
Sinuses: 0= no mucosal thickening, 1= partial opacification, 2= total opacificiation  
OMC: 0= not occluded, 2=obstructed  
CT evidence of inflammation of the sinuses will be defined as mucosal thickening of at least one 
paranasal sinus and does not have to be severe enough to be classified as “partial 
opacification” or have a Lund and MacKay score of 1 or greater.  
 
Data Collection 
Sources of Research Material:  All research-related information, including responses to the 
selected patient-reported outcome measures, will be captured electronically..  Week 2, Week 4, 
and Week 6 patient-reported outcome measures will be captured via an email sent to subjects 
with direct linkage to REDCap™ (Research Electronic Data Capture). All data will be stored in a 
specially designed database created by staff in the Clinical Outcomes Research Office using 
REDCap™. Patient confidentiality will be maintained through the use of unique patient ID. 
 
Assessment of Treatment Efficacy: The change in the average SNOT-22 scores between 
baseline and eight weeks will serve as the primary outcome measure in this study and will be 
calculated as: 
 
Primary Outcome Measure, ∆SNOT-22 = SNOT-22baseline — SNOT-228-week follow up. 
To assess the trajectory of change within subjects randomized to the two treatment arms the 
baseline, two-week, four-week, six-week, and eight-week SNOT-22 assessment will be 
compared.  
 
Assessment of Treatment Safety: As described above, 10 participants from each study arm will 
be selected for a cosyntropin test to assess for effects of mometasone nasal irrigation on the 
HPA axis. Treatment safety will also be assessed by patient interview and will include collection 
of adverse events experienced by the patient during the eight-week participation. 
 
Risk Assessment: Mometasone has a potent glucocorticoid activity and weak mineralocorticoid 
activity. As an inhaled product, mometasone has an onset of action in 24 hours and peak effect 
between 1-4 weeks. The drug is well-tolerated and the more frequent side effects include: nose 
irritation, epistaxis, lightheadedness, and upset stomach. At recommended daily doses in both 
pediatric and adult patients, no adverse effects were seen on the HPA axis. 29  
 
Data and Safety Monitoring: The Clinical Outcomes Research Office (CORO) created a set of 
Standard Operating Procedures (SOPs) for the conduct of clinical research.  These SOPS are 
developed, in part, from and are compliant with Institutional guidelines for the conduct of human 
research. The specific monitoring plan for this study is based on the potential risk of 
participation and size and complexity of the planned investigation.  Based on these 
considerations, this study will have a monitoring board comprised of Dr. Piccirillo and Ms. 


                                                                                                                                            Page 15 of 19 
 
Kukuljan knowledgeable about the risks of topically applied glucocorticosteroid, nasal anatomy, 
and Dr. Kallogjeri, the study biostatistician. The monitoring board will meet to review data at 
least every 6 months.  All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse 
Event will be investigated by the monitoring team. All SAEs will be reported to Washington 
University HRPO.  
 
Statistical Analysis: Comparison of within subject difference in SNOT22 scores between 
baseline and eight-week follow-up between the 2 treatment groups will be the primary outcome 
measure.  A clinically meaningful change is defined as a change of 9 or more points on the 
SNOT22 (scored as the average per item value for each of the 22 items). The change in 
SNOT22 is calculated as: ∆SNOT-22 = SNOT-22baseline — SNOT-228-week follow-up. Independent 
samples t-test will be used to test for statistically significant difference in ∆SNOT-22 between 2 
treatment groups. The statistical significance of the observed difference in the percentage of 
subjects who achieve a clinically meaningful difference will be assessed with the chi-square 
statistic.  The 95% confidence interval around the observed difference in the percentage of 
subjects who achieve a clinically meaningful difference will be calculated. 
 
To assess the time trajectory of change within subjects randomized to the two treatment arms, 
the baseline, 2 week, 4 week, 6 week, and 8 week SNOT-22 assessments will be computed and 
compared.  Within group differences will be compared using a repeated measure ANOVA. A 
general linear model (GLM) approach will be used to explore through the testing of an 
interaction effect (treatment group x time) whether the magnitude and pattern of change in 
SNOT-22 scores at baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks are different between 
the 2 treatment groups. In addition to allowing for exploration of the interaction effect, the GLM 
model allows for evaluation of estimated means after controlling for potential confounders. A 
robust regression model will be used if the assumption of the GLM model will not be met. 
The distribution of responses on the Clinical Global Impression (CGI) scale will be calculated 
within each intervention arm and the difference in responses between the two intervention arms 
will be compared for statistical significance with the chi-square statistic.  
 
All statistical analyses will be performed with the appropriate statistical software e.g. SAS, 
SPSS. Statistical significance will be defined as a two-tailed test of significance p value of 0.05 
or less. 
Stopping rules based on the work of O'Brien and Fleming 38 for the conduct of clinical trials will 
be followed. An Intention-to-Treat analysis will be used for the final data analyses.  
 
Sample Size Calculations: The sample size for this study was calculated based on achieving a 
difference of 9 points or more on SNOT-22 scores. Thus, to be able to detect with 80% power at 
the 2-sided alpha level of 0.05 a difference of 9 points or greater between the 2 treatment 
groups, a total of 50 subjects- 25 subjects per group- will be necessary. With an anticipated 
15% drop out/non-compliance rate, the total sample size planned for this study will be 44 
subjects.  
Remuneration: Subjects will receive $50 after baseline and $50 at final visit and upon 
successful completion of trial.   
For subjects who complete the coynstropin test, they will receive up to an additional $100. 
Subjects will receive $50 after the baseline cosyntropin test and another $50 following the 
second cosyntropin test.  
 
Timeline of the Study 


                                                                                                                                            Page 16 of 19 
 
Subjects will be enrolled in the study for a total of eight weeks.  Given the volume of patients 
seen at the Adult Otolaryngology service with diagnosis of CRS, we anticipate it will take one 
year to complete enrollment. 
 
 
Calendar of Events (Patient) 
Study Activity 
Baseline 
(Time 0) 
Week 1 
Weeks 2,4,6 
Week 8 
Consent 
X 
 
 
 
Randomization X 
 
 
 
SNOT-22 
X 
 
X 
X 
Cosyntropin 
test with blood 
draw 
X 
 
 
X 
ACE-27 
Comorbidity 
X 
 
 
 
ENT Physical 
examination w/  
Endoscopic 
examination* 
X 
 
 
X 
Radiological 
Examinations 
(ex. CT sinus)* 
X 
X 
X 
X 
Written 
instructions for 
administration 
of intervention 
X 
 
 
 
Intervention -  
mometasone  
nasal irrigation 
or 
mometasone 
nasal spray 
 
X 
X 
X 
Global Clinical 
Impression 
X 
X 
X 
X 
Questionnaire 
for Olfactory 
Dysfunction 
X 
 
 
X 
Olfactory 
Dysfunction 
Outcomes 
Rating 
(ODOR) 
X 
 
 
X 
UPSIT 
X 
 
 
X 
Participant 
Stipend 
X 
 
 
X 
* Results only from nasal endoscopic examination and radiological examination performed for 
clinical purposes during the study will be collected for research purposes. 


                                                                                                                                            Page 17 of 19 
 
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