Clinical trial NCT03979209
Conditions: Chronic Rhinosinusitis (Diagnosis)
Keywords: Cortisol Suppression Mometasone Chronic Rhinosinusitis Steroid Irrigations
Sponsor: Rush University Medical Center
Start date: 2019-01-14; Completion date: 2022-07-28
Enrollment: 16 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In the United States, more than 30 million people are diagnosed with sinusitis each year. Moreover, chronic sinusitis effects approximately 15% of the U.S. population and is one of the most common chronic illnesses in America. Budesonide and mometasone nasal sprays are used to relieve sneezing, runny, stuffy, or itchy nose caused by hay fever or other allergies (caused by an allergy to pollen, mold, dust, or pets).

The objective of this study is to determine the incidence of cortisol suppression with the use of mometasone irrigations in varying doses. Low levels of cortisol can cause weakness, fatigue, and low blood pressure.

In using nasal sprays, a drug may enter the body's circulation through direct local absorption in the nasal mucosa or oral absorption of any swallowed medication. Some people can reduce symptom severity using medication, including antihistamines and anti-inflammatory drugs. Nasal irrigation - the flooding of the sinus cavity with warm saline solution - can help to reduce sinus congestion and is often recommended by otolaryngologists for a variety of sinus conditions. The goal of nasal irrigation is to clear excess mucus and foreign debris out of the sinuses, and to moisturize the mucosal membrane. The practice has been subjected to clinical testing and has been found to be safe and beneficial with no apparent side effects.

The addition of budesonide to nasal irrigations has become common practice in the treatment of chronic rhinosinusitis. Mometasone has been shown to be an alternative to budesonide with increased local effects and lower absorption by the body. Studies have shown that saline irrigation treatments show greater effects versus saline spray for providing short-term relief of chronic nasal and sinus symptoms.

There is limited data on the use of mometasone in nasal irrigations. Subjects to be included in the study are those with a diagnosis of chronic rhinosinusitis, with or without nasal polyps and who have had prior endoscopic sinus surgery. This study will test 3 different concentrations of mometasone in a nasal irrigation. Patients will receive either 1 milligram mometasone in their nasal irrigations, 2 milligrams of mometasone, or 4 milligrams of mometasone. The dose assignment will be determined by the treating physician. After 12 weeks of entering this study and use of the mometasone irrigations, there will be a blood draw to compare morning cortisol levels to a baseline blood draw.

Detailed description:
Sinusitis is inflammation of the sinuses that results in symptoms such as thickened nasal drainage, nasal congestion and facial pain or pressure. Because sinusitis is often preceded by and almost always accompanied by, inflammation of the nasal mucosa, the term "rhinosinusitis" is used by ENT (ear, nose and throat) physicians to replace the term "sinusitis." Viruses, bacteria, and nasal allergies are common causes of inflammation. The inflamed, swollen mucosa of the nasal and sinus cavities leads to obstruction of the openings of the sinuses. Unable to circulate air and eliminate the secretions that are normally produced, the sinuses then become an ideal environment for bacterial infection.

Sinusitis is categorized into the following types according to the duration of symptoms:

Acute - symptoms are present for 4 weeks or less; Subacute - symptoms are present for more than 4 weeks, but less than 12 weeks; Chronic - symptoms are present for 12 weeks or greater; Recurrent Acute - 4 or more acute episodes occurring within 1 year, with resolution of symptoms between episodes; Acute exacerbation of chronic rhinosinusitis involves an episode of worsening symptoms in a patient with diagnosed with chronic rhinosinusitis.

In the United States, more than 30 million people are diagnosed with sinusitis each year. Moreover, chronic sinusitis effects approximately 15% of the U.S. population and is one of the most common chronic illnesses in America. Both budesonide and mometasone nasal sprays are used to relieve sneezing, runny, stuffy, or itchy nose caused by hay fever or other allergies (caused by an allergy to pollen, mold, dust, or pets). These nasal sprays are in the class of drugs called corticosteroids. They work by blocking the release of certain natural substances that cause allergy symptoms.

The objective of this study is to determine the incidence of cortisol suppression with the use of nasal mometasone irrigations in varying dosages.

Low levels of cortisol can cause weakness, fatigue, and low blood pressure. In using nasal sprays, a drug may enter the body's circulation through direct local absorption in the nasal mucosa or oral absorption of any swallowed medication. Some people can reduce symptom severity using medication, including antihistamines and anti-inflammatory drugs. Nasal irrigation - the flooding of the sinus cavity with warm saline solution - can help to reduce sinus congestion and is often recommended by otolaryngologists for a variety of sinus conditions. The goal of nasal irrigation is to clear excess mucus and foreign debris out of the sinuses, and to moisturize the mucosal membrane. The practice has been subjected to clinical testing and has been found to be safe and beneficial with no apparent side effects.

The addition of budesonide to nasal irrigations has become common practice in the treatment of chronic rhinosinusitis. Mometasone has been shown to be an alternative to budesonide with increased local effects and lower absorption by the body. Studies have shown that saline irrigation treatments show greater effects versus saline spray for providing short-term relief of chronic nasal and sinus symptoms. There is limited data on the use of mometasone in nasal irrigations.

The sample size for this study will be 45 patients. Patients will sign the consent form and get a baseline morning cortisol blood draw to confirm eligibility. Once enrolled, they will be instructed on how to perform the nasal irrigation twice a day with a 240 milliliter saline filled Neilmed bottle. Patients will receive either the 1 milligram mometasone dose, 2 milligram mometasone dose, or 4 milligram of mometasone dose. The dose assignment will be determined by the treating physician. After 12 weeks of continuous use of the mometasone irrigation, there will be a repeat morning blood draw to compare cortisol levels to the baseline blood draw.

Scientific Review:

The addition of budesonide to nasal irrigations has become common practice in the treatment of chronic rhinosinusitis. The dose of budesonide 0.5 milligrams/2 milliliters was chosen as a result of convenience, as budesonide respules are commercially available as an inhalation in the treatment of asthma. Mometasone is an alternative to budesonide with improved pharmacokinetics resulting in increased local efficacy and lower systemic absorption, however, data is limited in its use as a topical irrigation formulation.

There is relevant literature available discussing the pharmacokinetic profile of budesonide and mometasone used intranasally. Following intranasal administration a drug may enter systemic circulation through direct local absorption in the nasal mucosa or oral absorption of any swallowed medication. The intranasal bioavailability of budesonide and mometasone through nasal mucosa have been measured at 34% and less than 0.1% respectively. If a drug enters systemic circulation through the nasal mucosa, the medication is subject to plasma protein binding. When a medication is protein bound it is not bioactive and thus reduces the potential for systemic adverse effects. Approximately 85-90% of budesonide is bound to plasma proteins after entering systemic circulation. Alternatively, mometasone is 99% protein bound at clinically relevant concentrations. Therefore, budesonide is bioactive at 10-15 times the concentration of mometasone in the serum due to plasma protein binding.

A portion of the drug may also be cleared from the sinuses into the throat and swallowed, making it available for gastrointestinal absorption. Medications absorbed through the gastrointestinal tract are subject to first pass hepatic metabolism which largely determines the amount of medication which reaches systemic circulation. Approximately 90% of swallowed budesonide is metabolized by the liver during first pass metabolism7. On the other hand, when mometasone is swallowed and undergoes first pass metabolism, 99% of the drug is eliminated leaving only 1% of the drug to enter the circulation.

A desired pharmacokinetic property of intranasal steroids is high lipophilicity. Higher lipophilicity leads to increased intranasal absorption as well as prolonged retention in the nasal tissue. Longer retention of the steroid in nasal tissue results in increased exposure to the glucocorticoid receptor. The relative lipophilicity of budesonide and mometasone are 3,980 and 50,000 respectively. Thus, mometasone has twelve times higher lipophilicity than budesonide.

There is current relevant data to assess the safety of mometasone administered intranasally. A review of 20 clinical trials with more than 6,000 patients worldwide at doses up to 20 times the recommended daily dose found no detectable effect of mometasone on the hypothalamic-pituitary-adrenal axis (HPA). Additionally, mometasone at high doses, did not cause atrophy to the nasal mucosa. Intranasal mometasone at a dose of 1600 micrograms, which is 4 times the recommended dose administered daily to human volunteers for 29 days showed no incidence of adverse effects. The effects of oral mometasone on HPA axis function has also been studied. Oral mometasone was administered at doses of 2, 4, and 8 milligrams to 24 healthy male volunteers with no significant change in plasma or urinary cortisol from placebo.

Arms: arm 1: 1mg capsule dissolved in 240mg saline solution nasal irrigation arm 2: 2mg capsule dissolved in 240mg saline solution nasal irrigation arm 3: 4mg capsule dissolved in 240mg saline solution nasal irrigation
Interventions: intervention 1: Nasal Mometasone Rinse
Intervention descriptions: intervention 1: Nasal irrigation twice a day (BID) of assigned dose.

Protocol documents:
ICF_002.pdf: 
Consent Version Date: October 24, 2018
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Investigator: Bobby Tajudeen, MD
Contact Information: Rush Department of Otolaryngology, 1611 W. Harrison St. Ste. 505, 
Chicago IL 60612   312-942-6100
Title of Study: Potential for cortisol suppression with the use of high volume nasal 
mometasone irrigations in varying dosages
Sponsor: Rush Department of Otolaryngology; AdvancedRx, Plymouth Meeting, PA
Subject Information Sheet and Consent Form
Introduction
You are being invited to take part in this research study.  Before you decide, it is important for 
you to understand why the research is being done and what it will involve.  Please take the time 
to read the information in this form carefully, as it may contain words you do not understand.  
You may wish to discuss it with your doctor, family, and friends.  If there is anything that you do 
not understand or you would like more information, please ask questions, and the study doctor or 
study staff will try their best to answer them. Once the study has been explained and you have 
had all your questions answered to your satisfaction, you will be asked to sign this form if you 
wish to participate. Before anything is done for this study, you must sign this form.  A copy of 
this signed form will be given to you.  
You do not have to take part in this study.  You are free to withdraw from this study at any time 
you choose without giving a reason.  This will not affect any future care you will receive.  No 
promises can be made about the outcome of this as far as your current condition, either positive 
or negative.  People who take part in research are called “subjects” instead of “patients.”
Why are you being invited to participate in this study?
You are being asked to take part in this study because you are older than 18 years and suffer 
from chronic rhinosinusitis (CRS), and you have had a previous endoscopic sinus surgery. 
What is the purpose of this study?
The purpose of this study is to determine the safety of high-volume steroid irrigations of the 
sinuses, using a steroid formulation that may prove superior to more traditional steroid rinses.   
Nasal steroid irrigations are one treatment that many otolaryngologists (ear, nose, and throat 
doctors) use to treat CRS effectively. Previous studies have demonstrated that steroid irrigation is 
overall safe, and in this study, an alternative form of steroid rinse with increased safety profile 
will be employed and compared.  This study will study the impact of daily Mometasone nasal 
irrigations on the hormones of the body. Mometasone is commercially available as a nasal spray 
and lotion, but is not approved by the United States Food and Drug Administration (FDA) in a 
capsule product for nasal irrigation, that will be provided in this study.  
How many study subjects are expected to take part in the study?
We expect to enroll 45 subjects in the study at Rush University Medical Center.
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What will you be asked to do?
You will be evaluated for eligibility for the study. Baseline demographic (age, sex, race, national 
origin, etc.) Laboratory data including AM cortisol level and pregnancy testing for women of 
child bearing capacity and medical history data will be collected upon enrollment. Please inform 
the study doctor about all medications you are currently (or recently) taken, including 
prescription, over-the-counter or herbal medications.  Do not start any new medications or 
supplements while in the study without discussing them with the study doctor 
You will be assigned to one of three possible Mometasone dosage groups 1 milligrams, 2 
milligrams, or 4 milligrams, based on first come first serve randomization (15 subjects in each 
dosage group) and instructed on how to perform twice-daily steroid irrigations (8 ounces of salt 
water per rinse).  At follow up visits, you will be examined as you would normally as part of care 
for your sinus problem. A laboratory blood test (approximately 2 tablespoons) will be drawn 
twelve weeks after continued use of the irrigation, to ensure that no hormone imbalances have 
occurred. It will measure morning cortisol levels in the body, so you will need the blood test to 
be drawn as close to 7 a.m. as possible. The body’s cortisol levels peak in the morning and 
decline through the day.  If you require oral (by mouth) steroids for medical reasons, the blood 
level will be delayed by one month from oral steroid use. If your morning cortisol levels are 
abnormal, the test will be repeated and if again abnormal you will have to follow up with an 
endocrinologist. You or your health plan insurance company will need to pay for the visits to the 
endocrinologist. 
How long will you be in the study?
The study has been planned for a one year duration.  Your participation will end after your 
cortisol level is drawn after 12 weeks of continuous topical irrigation use or in case of oral (by 
mouth) steroids for medical reasons, the blood level will be delayed by one month from oral 
steroid use.  
You may be removed from this study without your consent.  Possible reasons may be that the 
study doctor decides that continued participation in the study will be harmful to you, you will 
need a treatment not allowed on the study, or the study is canceled.
What are the possible risks of the study?
Risks from nasal steroid irrigation
Nasal steroid irrigations are well-tolerated and adverse (bad) effects are rare. Most adverse 
effects associated with topical steroid use are extrapolated (derived) from known systemic 
(throughout the body) steroid adverse effects these include
1. Increased pressure in the eye which causes severe eye and head pain, 
2. Reduced hormone production by the adrenal glands. Low levels of hormone (cortisol) 
can cause weakness, fatigue (feeling tired), and low symptomatic blood pressure.  
3. Local nasal effects like nasal septum perforation, irritation and bleeding from nose 
(epistaxis)
4. Hypersensitivity reactions including rash, itching of skin (pruritus) difficulty breathing 
(wheezing) and swelling beneath the surface of the skin (angioedema). Swelling may 
occur on the feet, hands, eyes, and lips. In more severe cases, the swelling can spread to 
other parts of the body. Discontinue the study drug if such reaction occurs and seek 
immediate medical attention.  
Mometasone is believed to have very low systemic absorption and has a better safety 
profile than current options for steroid rinses, further limiting the risk of these adverse 
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effects. If you have any such adverse effects you should let your study doctor know or 
seek immediate medical attention. 
Pregnancy risks 
Women 
You may not participate in this study if you are pregnant or breastfeeding.  A pregnancy test is 
required and will be given before you can receive the study treatment. You are responsible for 
using an effective birth control method such as birth control pill, barrier method, (such as 
condoms or diaphragm), intrauterine device (IUD), hormone implants or surgical sterility while 
you are taking part in this study. If you become pregnant, you must notify the study doctor 
immediately.
Are there benefits to taking part in the study?
There may be no direct benefit to you. We hope that you will have a good response to the 
treatment, but this cannot be guaranteed.
Others may benefit from the information learned in this study. 
What other options are there?
Instead of participating in this study, you may choose another form of treatment such as:
Getting treatment or care for your CRS without being in this study;
Taking part in another study;
Getting no treatment.
How will you receive medical supply such as medicines etc.?
Advanced Rx will receive your information such as name, contact number, address to ship the 
medical supplies.
What about confidentiality of your information?
Records of participation in this research study will be maintained and kept confidential as 
required by law. Any health information of yours that is used in the present study will be de-
identified prior to storing it for use in later analysis. This de-identified data will be stored on a 
secure server within Rush University Medical Center.
If you withdraw from this study, the data already collected from you may not be removed from 
the study records.  The study doctor and/or study staff may ask you whether they can continue to 
collect follow-up data on you.  
Your identity will not be revealed on any report, publication, or at scientific meetings. 
In order to conduct the study, the study doctor, Dr. Tajudeen, will use and share de-identified 
personal health information about you.  This includes information already in your medical 
record, as well as information created or collected during the study.  Examples of the information 
that may be shared include your medical history, physical exam and laboratory test results.  The 
study doctor will use this information about you to complete this research, however, it will not be 
associated with your name, photo, or any other identifying information.
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Confidentiality and disclosure of your personal information is further described in the attachment 
to this form.  The attachment is titled HIPAA Authorization to Share Personal Health 
Information in Research (2 pages).
The Rush Institutional Review Board (IRB) will have access to your files as they pertain to this 
research study. The IRB is a special committee that reviews new and ongoing human research 
studies to check that the rules and regulations are followed regarding the protection of the rights 
and welfare of human subjects.
A description of this clinical study 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 the Web site at any time. 
Please note information may not be available on ClinicalTrials.gov until the study is completed. 
What are the costs of your participation in this study?
The cost of a baseline cortisol blood draw and pregnancy tests should be covered by your 
insurance provider as they are standard of care.  Insurance coverage for the baseline morning 
cortisol blood draw and a pregnancy test will be checked by office staff prior to enrollment in 
the study. If not covered, you can choose to cover the cost.
You and/or your health/dental plan/ insurance company will need to pay for regular follow-up 
care for your CRS. You will be responsible for all costs that are not paid by your insurance 
company. You should check with your insurance company before you enroll in this research 
study.
You will be required to obtain a laboratory morning cortisol test after 12 weeks of 
continuous use of Mometasone irrigation that will be reimbursed as part of the study. The 
study drug mometasone will be provided free to participants in the study twice daily for 12 
weeks.
Will you be compensated or paid?
You will not be paid for your participation in this study.
What happens if you experience a research related injury?
If you experience any injury or illness as a direct result of your participation in this research 
study, immediate treatment will be provided. However, the cost of that treatment will be 
billed to you or your insurance company.  Please check with your insurance company 
regarding coverage. If you have any medical problems during the study, please contact the 
study doctor.  He or she will explain your treatment options to you and/or help you find a 
place to get treatment. 
Rush University Medical Center has no program for financial compensation or other 
forms of compensation for injuries which you may incur as a result of participation in this 
study.
What happens if you need emergency care?
If you need emergency care while you are participating in this study, it is important that you tell 
emergency personnel of your participation in this study and notify the study doctor as soon as 
possible. 
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Whom do you call if you have questions or problems?
Questions are encouraged.  If there are any questions about this research study or if you 
experience a research related injury, please contact: Dr. Bobby Tajudeen at (312) 942-6100. 
Questions about the rights of research subjects may be addressed to the Rush Office of Research 
Affairs at 1-800-876-0772.
By signing below, you are consenting to participate in this research study.  You have read the 
information given or someone has read it to you. You have had the opportunity to ask questions, 
which have been answered satisfactorily to you by the study staff. You do not waive any of your 
legal rights by signing this consent form. 
SIGNATURE BY THE SUBJECT:
Name of Subject
Signature of Subject
Date of Signature
SIGNATURE BY THE INVESTIGATOR/INDIVIDUAL OBTAINING CONSENT:
I attest that all the elements of informed consent described in this consent document have been 
discussed fully in non-technical terms with the subject.  I further attest that all questions asked by 
the subject were answered to the best of my knowledge.  
Signature of Individual Obtaining Consent
Date of Signature
 Check here if the Individual Obtaining Consent observed the signing of this consent 
document and can attest, to the best of their knowledge, the person signing the consent form is 
the subject and the person signing the form has done so voluntarily.  By checking this box, the 
Individual Obtaining Consent does not need to sign on the Witness signature line (below).
SIGNATURE BY WITNESS/INTERPRETER:
(for use if this consent is being used as a written summary of the research along with a 
short form consent OR when the person obtaining consent is not the witness):
I observed the signing of this consent document and attest that, to the best of my knowledge, the 
person signing the consent form is the subject and the person signing the form has done so 
voluntarily.
Signature of Witness/Interpreter
Date of Signature
Check here if a separate witness signature is not necessary.
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SIGNATURE OF THE PRINCIPAL INVESTIGATOR:
I attest that I am aware of the enrollment of this subject in the study discussed in this consent 
document.
Signature of the Principal Investigator
Date of Signature
Check here if Principal Investigator obtained consent and a separate signature is not required.
ORA: 17121505-IRB02-CR02   Date IRB Approved: 6/28/2020   Expiration Date: 6/28/2021

Prot_000.pdf: 
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Protocol Title: Potential for Cortisol Suppression with the Use of High Volume Nasal 
                         Mometasone Irrigations in Varying Dosages
Principal Investigator: Bobby Tajudeen, MD
Address: Rush University Medical Center, Department of Otorhinolaryngology – Head
                and Neck Surgery, 1611 W. Harrison Street, Suite 550, Chicago, IL  60612
Protocol Version Date: April 20, 2018
Objective:
To determine incidence of cortisol suppression with the use of high volume nasal 
Mometasone irrigations in varying dosages.
Study Duration: 1 year 
Timeframe of study treatment and participation: 12 – 16 weeks 
Inclusion Criteria:
•
Age 18+
•
Diagnosis of Chronic Rhinosinusitis, with or without nasal polyposis
•
History of prior endosopic sinus surgery
o
Must include at least ethmoidectomy with maxillary antrostomy
Exclusion Criteria:
•
Exposure to systemic corticosteroids within one month of the date of enrollment 
in to the study.
•
Adrenal insufficiency 
•
Liver disease
•
Use of oral estrogens in women 
•
Morbid obesity (BMI > 38)
•
Concurrent pregnancy
•
Use of medications which may alter HPA axis(refer to Drugs that affect HPAA)
•
Ciliary dysmotility, cystic fibrosis, sarcoidosis, systemic vasculitis, IgG or IgA 
deficiency, known pituitary or adrenal disease
Intervention:
1. Pre study  variables to be collected
a. Demographic data including MRN, Name, Age, Sex, BMI 
b. Laboratory data including AM cortisol level and pregnancy testing. 
c. Imaging data 
d. Pertinent medical history related to sinus disease 
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e. Concomitant medication H/o ( Avoid drug interactions – refer to the drug 
interactions section)
f.
Hx of arenal insufficiency and liver disease 
g. Asthma history
h. Allergy history
i.
ASA intolerance
j.
Smoking history
k. Lund-Mackay radiographic score
l.
Modified Lund-Mackay endoscopic score
i. Only if able to be used preoperative. May be a strictly postoperative 
scoring system.
m. Presence/absence of polyps
2. Enrolled pts will be randomized on first come first serve into one of the three 
Mometasone irrigation groups (15 subjects in each dose study group)  
a. 1mg, 2mg, 4mg BID nasal sinus irrigation dose (see pharmacokinetic 
calculations in rationale)
3. Patients will be followed and treated as standard care. No additional patient visits 
will be required as part of the research protocol.
4. AM cortisol testing will be performed at 12 – 16 weeks after 12 weeks of 
continuous topical irrigation use 
a. Testing will be performed between 6-10 am
i. This is the standard in the literature
ii.  RUMC lab hours 7am-5:30pm M-F
b. If patient requires steroid burst for medical reasons, testing schedule will 
be delayed 1 month from oral steroid use
5.  Subjects with abnormal blood cortisol levels after 12 weeks of continuous topical 
irrigation will have a repeat blood cortisol level tested and if abnormal will be 
follow up with an Endocrinologist.
Drugs which affect the HPAA:
•
Mifepristone
•
Cyproheptadine, ketanserin, ritanserin, metergoline
•
Bromocriptine, cabergoline
•
Reserpine
•
Valproic acid
•
Octreotide, lanreotide, pasireotide
•
Pioglitazone, rosiglitazone
•
Metyrapone, Trilostane, mitotane, aminoglutethimide, ketoconazole, fluconazole, 
etomidate
•
Sertraline, citalopram, Trazodone
•
Clonidine
•
MDMA, cocaine, amphetamine
•
Methadone, buprenorphine, naltrexone
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•
Olanzapine, quetiapine, imipramine, desimipramine, clomipramine, mirtazapine
•
Medroxyprogresterone, megestrol, Raloxifene
Drug Interactions 
•
Avoid combination with Desmopressin 
•
Monitor therapy while on 
A. CYP3A4 Inhibitors (Strong) Interacting Members Atazanavir; Boceprevir; 
Clarithromycin; Cobicistat; Darunavir; Idelalisib; Indinavir; Itraconazole; 
Ketoconazole (Systemic); Lopinavir; MiFEPRIStone; Nefazodone; Nelfinavir; 
Ombitasvir, Paritaprevir, and Ritonavir; Ombitasvir, Paritaprevir, Ritonavir, 
and Dasabuvir; Posaconazole; Ritonavir; Saquinavir; Telaprevir; 
Telithromycin; Voriconazole 
B. Ceritinib.
C. Ritodrine
Mometasone Study Rationale
The addition of budesonide 0.5 mg/2 ml respules to nasal irrigations has become 
common practice in the treatment of chronic rhinosinusitis1-2.  The dose of budesonide 
0.5 mg/2 ml was chosen as a result of convenience, as budesonide respules are 
commercially available as an inhalation in the treatment of asthma.  Mometasone is an 
alternative to budesonide with improved pharmacokinetics resulting in increased local 
efficacy and lower systemic absorption, however, data is limited in its use as a topical 
irrigation formulation.  
There is relevant literature available discussing the pharmacokinetic profile of 
budesonide and mometasone used intranasally.  Following intranasal administration a 
drug may enter systemic circulation through direct local absorption in the nasal mucosa 
or oral absorption of any swallowed medication3.  The intranasal bioavailability of 
budesonide and mometasone through nasal mucosa have been measured at 34% and 
<0.1% respectively4.  If a drug enters systemic circulation through the nasal mucosa, the 
medication is subject to plasma protein binding.  When a medication is protein bound it 
is not bioactive and thus reduces the potential for systemic adverse effects. 
 Approximately 85-90% of budesonide is bound to plasma proteins after entering 
systemic circulation5.  Alternatively, mometasone is 99% protein bound at clinically 
relevant concentrations6.  Therefore, budesonide is bioactive at 10-15 times the 
concentration of mometasone in the serum due to plasma protein binding.
A portion of the drug may also be cleared from the sinuses into the throat and 
swallowed, making it available for gastrointestinal absorption.  Medications absorbed 
through the gastrointestinal tract are subject to first pass hepatic metabolism which 
largely determines the amount of medication which reaches systemic circulation. 
 Approximately 90% of swallowed budesonide is metabolized by the liver during first 
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pass metabolism7.  On the other hand, when mometasone is swallowed and undergoes 
first pass metabolism, 99% of the drug is eliminated leaving only 1% of the drug to enter 
the circulation7.           
A desired pharmacokinetic property of intranasal steroids is high lipophilicity. 
 Higher lipophilicity leads to increased intranasal absorption as well as prolonged 
retention in the nasal tissue3.  Longer retention of the steroid in nasal tissue results in 
increased exposure to the glucocorticoid receptor8.  The relative lipophilicity of 
budesonide and mometasone are 3,980 and 50,000 respectively6,9.  Thus, mometasone 
has twelve times higher lipophilicity than budesonide.            
In order to determine the proper dose of mometasone, it is important to take into 
account the volume of nasal irrigation that will remain in the sinus cavity. In patients who 
have undergone endoscopic sinus surgery, after performing a nasal irrigation with a 240 
ml saline filled Neilmed bottle, the result is 1.2% to 5% of the solution remaining in the 
sinuses10.  Therefore, the maximum  amount of fluid left in the sinuses after a 240 ml 
nasal irrigation is 5% of the total volume or 12 ml.  Applying this data one may estimate 
the maximum absorption of mometasone added to a 240 ml saline filled Neilmed bottle 
for irrigation.  
•
Mometasone 1 mg capsule dissolved in 240 mg
o
1 mg/ 240 ml = 0.00416 mg/ml or 4.16 mcg/ml

Max volume that can be retained in sinuses is 12 ml

12 ml x 4.16 mcg/ml = 50 mcg

Medication dosed twice daily, therefore total daily dose = 100 mcg
•
Mometasone 2 mg capsule dissolved in 240 mg
o
2 mg/ 240 ml = 0.00833 mg/ml or 8.33 mcg/ml

Max volume that can be retained in sinuses is 12 ml

12 ml x 8.33 mcg/ml = 100 mcg

Medication dosed twice daily, therefore total daily dose = 200 mcg
•
Mometasone 4 mg capsule dissolved in 240 mg
o
4 mg/ 240 ml = 0.0166 mg/ml or 16.6 mcg/ml

Max volume that can be retained in sinuses is 12 ml

12 ml x 16.6 mcg/ml = 200 mcg

Medication dosed twice daily, therefore total daily dose = 400 mcg
Mometasone nasal spray is currently FDA approved at a dose of 2 sprays (100 
mcg) in each nostril twice daily for the treatment of nasal polyps.  Total daily dose is 400 
mcg11.  Therefore even at a dose of mometasone 4 mg used in a 240 ml nasal irrigation, 
the total daily dose is equivalent to that of the mometasone nasal spray.    
There is current relevant data to assess the safety of mometasone administered 
intranasally.  A review of 20 clinical trials with more than 6,000 patients worldwide at 
doses up to 20 times the recommended daily dose found no detectable effect of 
mometasone on the hypothalamic-pituitary-adrenal axis (HPA)12.  Additionally, 
mometasone at high doses, did not cause atrophy to the nasal mucosa12.  Intranasal 
mometasone at a dose of 1600 mcg, which is 4 times the recommended dose 
administered daily to human volunteers for 29 days showed no incidence of adverse 
ORA: 17121505-IRB02   Date IRB Approved: 8/23/2018


5 of 5
effects11.  The effects of oral mometasone on HPA axis function has also been studied. 
 Oral mometasone was administered at doses of 2, 4, and 8 mg to 24 healthy male 
volunteers with no significant change in plasma or urinary cortisol from placebo13.  
   
References:
1.
Smith, K. A., French, G., Mechor, B., & Rudmik, L. (2016, March). Safety of longterm 
highvolume sinonasal budesonide irrigations for chronic rhinosinusitis. In International forum of 
allergy & rhinology (Vol. 6, No. 3, pp. 228-232).
2.
Soudry, E., Wang, J., Vaezeafshar, R., Katznelson, L., & Hwang, P. H. (2016, June). Safety 
analysis of longterm budesonide nasal irrigations in patients with chronic rhinosinusitis post 
endoscopic sinus surgery. In International forum of allergy & rhinology (Vol. 6, No. 6, pp. 568-
572).
3.
Derendorf, H., & Meltzer, E. O. (2008). Molecular and clinical pharmacology of intranasal 
corticosteroids: clinical and therapeutic implications. Allergy, 63(10), 1292-1300.
4.
Sastre, J., & Mosges, R. (2012). 1 Local and Systemic Safety of Intranasal Corticosteroids. 
Journal of Investigational Allergology and Clinical Immunology, 22(1), 1.
5.
Pulmicort(R) [package insert]. Wilmington, DE: AstraZeneca; 2000.
6. Hochhaus, G. (2008). Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal 
spray: potential effects on clinical safety and efficacy. Clinical therapeutics, 30(1), 1-13.
7.
Lipworth, B. J., & Jackson, C. M. (2000). Safety of inhaled and intranasal corticosteroids. Drug 
Safety, 23(1), 11-33.
8.
Corren, J. (1999). Intranasal corticosteroids for allergic rhinitis: how do different agents 
compare?. Journal of allergy and clinical immunology, 104(4), s144-s149.
9.
Brattsand, R. What factors determine anti-inflammatory activity and selectivity of inhaled 
steroids? Eur. Respir. Rev. 1997, 7, 356– 361.
10. Harvey, R. J., Debnath, N., Srubiski, A., Bleier, B., & Schlosser, R. J. (2009). Fluid residuals and 
drug exposure in nasal irrigation. Otolaryngology—Head and Neck Surgery, 141(6), 757-761.
11. Nasonex(R) [package insert]. Whitehouse Station, NJ: Merk & CO.,INC; 1997.
12. Davies, R. J., & Nelson, H. S. (1997). Once-daily mometasone furoate nasal spray: efficacy and 
safety of a new intranasal glucocorticoid for allergic rhinitis. Clinical therapeutics, 19(1), 27-38.
13. Brannan, M. D., Seiberling, M., Cutler, D. L., Cuss, F. M., & Affrime, M. B. (1996, January). Lack 
of systemic activity with intranasal mometasone furoate. In JOURNAL OF ALLERGY AND 
CLINICAL IMMUNOLOGY (Vol. 97, No. 1, pp. 62-62). 11830 WESTLINE INDUSTRIAL DR, ST 
LOUIS, MO 63146-3318: MOSBY-YEAR BOOK INC.
Parameter
Budesonide
Mometasone
Systemic bioavailability through nasal mucosa
34%
<0.1%
Drug remaining after first pass metabolism 
10%
1%
Plasma protein binding
85-90%
99%
Relative lipophilicity
3980
50,000
ORA: 17121505-IRB02   Date IRB Approved: 8/23/2018

SAP_001.pdf: 
 
Potential for Cortisol Suppression With the Use of High Volume Nasal 
Mometasone Irrigations in Varying Dosages. 
NCT03979209 
8/10/2021 
 
Statistical Analysis Plan 
 
An a priori analysis using G*3.0.10 Power was performed in order to determine 
adequate sample size. Using a Cohen's D of 1.0, alpha of 0.05 and power of 0.95, 
sample size was determined to be 13. Pre- and post-treatment morning cortisol 
serum levels were compared using a match paired, dependent sample Student's t-
test.8 Significance was established at P<0.05. All data acquired during this study 
were de-identified to protect patient privacy, and identifying information was 
only available to the principal investigator.