Clinical trial NCT02493257
Conditions: Nonallergic Irritant Rhinitis
Keywords: nonallergic irritant rhinitis nasal congestion rhinorrhea
Sponsor: The University of Texas Health Science Center, Houston
Start date: 2014-10-01; Completion date: 2019-08-02
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The proposed study seeks to investigate the effect of intranasal capsaicin treatment in patient with Non-allergic irritant rhinitis (NAIR), as well as evaluate optical rhinometry (ORM) as a means to quantify symptomatic improvement in NAIR patients during and after treatment.

Detailed description:
A study by Lambert et. al. (2012) was able to objectively identify patients with NAIR by intranasal capsaicin challenge followed by assessment with optical rhinometry. Studies have shown that capsaicin therapy can improve symptoms of patients historically identified with NAIR via visual analog scale (VAS) rating of symptoms and symptom surveys; however, there has been no study evaluating the capsaicin therapy on patients objectively identified as NAIR patients.

Multiple studies have demonstrated that intranasal capsaicin can improve nasal symptoms of NAIR patients. Regarding the usage of capsaicin, there is a product on the market: Sinus Buster which has capsaicin as the active ingredient. Numerous research papers have evaluated the efficacy and safety of Sinus Buster for the treatment of congestion in non-allergic rhinitis patients. However, the diagnosis of NAIR in these previous studies was based primarily on history. In addition, the primary outcome in these studies was symptomatic without any objective evaluation. The goal of this study will be two-fold: with patients objectively identified as NAIR patients via the optical rhinometer, we will re-evaluate the therapeutic action of intranasal capsaicin on the management of rhinitic symptoms. We expect that the patients will show significant improvement in their symptoms. We will then use optical rhinometry as a means to objectively monitor changes in symptoms in NAIR patients. We expect that post treatment, patients will no longer have the positive response previously seen on intranasal capsaicin challenge before receiving treatment. We hope to be able to establish optical rhinometry as an objective measurement of symptom improvement for NAIR symptoms, along with the subjective patient surveys.

Arms: arm 1: The capsaicin solution will be prepared by using the formula previously reported by Van Rijswijk et al; (0.1mmol/l) diluted in ethanol and 0.9% normal saline (19). Using the mucosal atomizer device (MAD), 0.8 milliliters (mL) will be delivered to each nasal cavity for a total of 24.4 ug per nasal cavity. 5 consecutive applications of capsaicin or placebo will be administered intranasally, with 1 hour between each application. arm 2: 100 μL of 1% ethanol in 0.9% saline solution. 5 consecutive applications of capsaicin or placebo will be administered intranasally, with 1 hour between each application.
Interventions: intervention 1: Capsaicin intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Double-Blinded Randomized Prospective Trial of Intranasal Capsaicin Treatment for Non-
Allergic Irritant Rhinitis 
 
NCT02493257 
 
Version Date: 11/18/2019 
 
 


IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
Protocol Title: Double-Blinded Randomized Prospective Trial of Intranasal Capsaicin 
Treatment for Non-Allergic Irritant Rhinitis 
 
Principal Investigator: Denna Zebda 
 
Co-Investigators: Amber Luong, MD PhD; Martin Citardi, MD; Samer Fakhri, MD 
 
Study Coordinator: Faramarz Ashoori, MD PhD 
 
Population: The study population will consist of patients with non-allergic irritant rhinitis 
(NAIR) as defined by history (symptoms of nasal congestion, rhinorrhea, nasal itching or 
sneezing upon exposure to nasal irritants) and positive optical rhinometer (Rhinolux™, Rhios 
GmbH, and Germany) response with intranasal challenge with capsaicin. Participants will be 
sought from those presenting to the outpatient Otolaryngology clinic at the University of Texas 
Medical School at Houston. Patients included in the study will be between the ages of 18 and 70 
with no history of sinonasal surgery, intranasal steroid use for more than 4 weeks, intranasal or 
systemic antihistamine for 3 days, intranasal or systemic decongestants for 3 days, chronic 
rhinosinusitis, inflammatory or granulomatous diseases, asthma, allergic rhinitis, 
immunocompromised state or radiation to the head and neck. 
 
Sample size: 11 participants will need to be recruited to each group (experimental and control) 
to detect a significant post-treatment change. In order to reach our target enrollment of 22 
participants we expect to screen 60 subjects. 
 
Number of sites: single site 
Study duration: 13 weeks 
Subject duration: 13 weeks 
General Information: The proposed study seeks to investigate the effect of intranasal capsaicin 
treatment in patient with Non-allergic irritant rhinitis (NAIR), as well as evaluate optical 
rhinometry (ORM) as a means to quantify symptomatic improvement in NAIR patients during 
and after treatment. 
 
Background Information: 
Rhinitis is defined as inflammation of the membranes lining the nose, characterized by 
symptoms including itching, rhinorrhea, and/or nasal congestion. It is a common clinical illness 
throughout the world and is consistently ranked among the most frequent of chronic illnesses, 
significantly affecting the quality of life of patients and their families. Non-allergic rhinitis is 
defined as rhinitis symptoms in the absence of an identifiable allergy, structural abnormality, or 
sinus disease. Non-allergic irritant rhinitis (NAIR) affects as many as 17 million Americans, and 
approximately 22 million suffer a combination of allergic rhinitis (AR) and NAIR (1). 
The pathophysiology of NAIR is largely unknown. It is described as a non-specific nasal 
hyper-reactivity that occurs on exposure to non-immunologic stimuli including changes in 
temperature, strong odors, and airborne irritants. Nasal mucosa is innervated by autonomic and 


IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
sensory neurons. Such stimulation of sensory fibers (C and Aδ) can lead to the irritative effects 
including sneezing, itching, rhinorrhea, and pain (2). Such effects are believed to be mediated by 
the trigeminal system. 
The trigeminal nerve fibers in the nasal cavity respond to a wide variety of chemical 
stimuli. One known receptor is the TRPV-1 vanilloid receptor. Capsaicin is one such ligand of 
the TRPV-1 receptor; however, the receptor is also activated by noxious temperatures and low 
extracellular pH (3). Stjarne et al showed that although capsaicin acts as an irritant in controls 
and rhinitic patients, those with NAIR reported increased rhinorrhea and nasal congestion (4). In 
animal studies, capsaicin has been shown to stimulate sensory C-fibers releasing substance P and 
calcitonin gene related peptide (CGRP), both potent vasodilators (5). However, repeated 
stimulation showed desensitization and degeneration of C-fibers (6), which is the basis for 
capsaicin usage in pain treatment. 
Currently, intranasal steroids are the only FDA approved agents used in NAIR. Topical 
applications of capsaicin have been used in the treatment of pain particularly in post-herpetic 
neuralgia, post mastectomy pain, and hypersensitivity disorders of the lower urinary tract (7-9). 
LaCroix et al has shown that repeated administration of intranasal capsaicin decreased nasal 
symptoms in NAIR patients (10). Although multiple studies using intranasal capsaicin have been 
shown to improve nasal symptoms of NAIR patients (11-13); there have been no studies in 
which NAIR patients were objectively identified and symptom improvement was objectively 
monitored. 
Optical rhinometry (ORM) has been proposed to be a useful instrument in the assessment 
of nasal blood flow, as an indirect measurement of nasal congestion (14). A positive correlation 
has been made between optical rhinometry and symptom scores for nasal congestion in nasal 
provocation testing (15). ORM has also been shown to correlate with changes in nasal cavity 
cross sectional area measured via acoustic rhinometry (16). In addition, our group recently 
reported that ORM following 0.05 mM capsaicin challenge can be utilized to identify NAIR 
patients (17). 
A study by Lambert et. al. (2012) was able to objectively identify patients with NAIR by 
intranasal capsaicin challenge followed by assessment with optical rhinometry (17). Studies have 
shown that capsaicin therapy can improve symptoms of patients historically identified with 
NAIR via visual analog scale (VAS) rating of symptoms and symptom surveys; however, there 
has been no study evaluating the capsaicin therapy on patients objectively identified as NAIR 
patients. 
Multiple studies have demonstrated that intranasal capsaicin can improve nasal symptoms 
of NAIR patients (11-13). Regarding the usage of capsaicin, there is a product on the market: 
Sinus Buster which has capsaicin as the active ingredient. Numerous research papers have 
evaluated the efficacy and safety of Sinus Buster for the treatment of congestion in non-allergic 
rhinitis patients (5, 12). However, the diagnosis of NAIR in these previous studies was based 
primarily on history. In addition, the primary outcome in these studies was symptomatic without 
any objective evaluation. The goal of this study will be two-fold: with patients objectively 
identified as NAIR patients via the optical rhinometer, we will re-evaluate the therapeutic action 
of intranasal capsaicin on the management of rhinitic symptoms. We expect that the patients will 
show significant improvement in their symptoms. We will then use optical rhinometry as a 
means to objectively monitor changes in symptoms in NAIR patients. We expect that post 
treatment, patients will no longer have the positive response previously seen on intranasal 
capsaicin challenge before receiving treatment. We hope to be able to establish optical 


IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
rhinometry as an objective measurement of symptom improvement for NAIR symptoms, along 
with the subjective patient surveys. 
 
Objectives: 
1. To establish optical rhinometry as an objective means of evaluating changes of NAIR 
symptoms after treatment. 
2. To re-evaluate the therapeutic action of intranasal capsaicin on the management of rhinitic 
symptoms in objectively defined NAIR patients. 
 
Study Design: 
The study will consist of patients with non-allergic irritant rhinitis (NAIR) as defined by 
history (symptoms of nasal congestion, rhinorrhea, nasal itching or sneezing upon exposure to 
nasal irritants) and positive optical rhinometer (Rhinolux™, Rhios GmbH, and Germany) 
response with intranasal challenge with capsaicin (17). Participants will be sought from 
volunteers and those presenting to the outpatient Otolaryngology clinic at the University of 
Texas Medical School at Houston. Patients included in the study will be between the ages of 18 
and 70 with no history of sinonasal surgery, intranasal steroid use for more than 4 weeks, 
intranasal or systemic antihistamine for 3 days, intranasal or systemic decongestants for 3 days, 
chronic rhinosinusitis, inflammatory or granulomatous diseases, asthma, allergic rhinitis, 
immunocompromised state or radiation to the head and neck. 
Allergy Testing to Identify and Exclude Subjects with Allergic Rhinitis 
All previously consented subjects with history consistent with NAIR will be screened 
with a skin prick test (Multi-Test II Lincoln Diagnostics, Decatur, IL USA) to 6 common 
allergens including dust mite, mixed mold extract, cat hair, grass pollen, insect extracts, and 
bermuda grass extract to exclude allergic rhinitis. Those with confirmed negative skin prick 
testing will be eligible for the study. 
Capsaicin Challenge and Optical Rhinometry 
The optical rhinometer apparatus is applied to either side of the nasal dorsum according 
to the manufacturer’s instructions. A one-minute baseline recording will be obtained and 
averaged. Capsaicin solution (Sigma Chemical, St. Louis, MO USA) will be diluted in 1% 
ethanol vv and 0.9% normal saline. 1% ethanol in 0.9% normal saline will serve as the vehicle 
solution. A mucosal atomizer device (MAdomizer, Wolfe Tory Medical, Inc Salt Lake City, UT 
USA delivering a 100 μl solution will be used to deliver a dose of capsaicin totaling 1.5 μg of 
caspsaicin (0.05 mM) to the anterior face of the inferior turbinate of each nare. The maximum 
change in optical density (OD) will be recorded. Patients with a maximum change in OD of at 
least 0.2 will be considered a positive response and included in the study. 
A composite symptom score will be recorded based a commonly used rhinitis rating 
system as recommended by the FDA for clinical trial studies on allergic rhinitis 
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/u 
cm071293.pdf). Each of the following 4 symptoms: nasal itching/tingling, nasal congestion, 
sneezing and rhinorrhea, will be rated on a 0-3 scale of severity (Appendix B) and a summed 
composite score will be recorded for each subject. 
 
Capsaicin Treatment Concentration 


IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
The capsaicin solution will be prepared by using the formula previously reported by Van 
Rijswijk et al; (0.1mmol/l) diluted in ethanol and 0.9% normal saline (19). Using the MAD, 
0.8mL will be delivered to each nasal cavity for a total of 24.4 ug per nasal cavity. 
 
Study Procedure: 
There will be a total of 4 visits. On the first visit, patients will be consented and undergo 
skin prick testing, the capsaicin challenge and Optical Rhinometry. Prior to undergoing the 
capsaicin challenge, a composite symptom score will be recorded. Patients with confirmed 
negative skin prick testing, and positive response on ORM will be eligible for the study and will 
be asked to return for treatment. Those who are not eligible will not be responsible for any costs 
associated with screening and will be compensated for parking as well as $25.00 for their time. 
At the second visit, the NAIR patients will have been randomized and blinded into two 
groups: Group A will be treated with vehicle spray; and Group B will be treated with the 
capsaicin spray. The PI will be blinded to the treatment. A member of the research team, which 
consists of Drs. Amber Luong, Martin Citardi, Samer Fakhri, and Faramarz Ashoori (research 
coordinator), will assist during the randomization and distribution of appropriate pre-made 
medications so that the PI and subjects remain blinded. 
5 consecutive applications of capsaicin or placebo will be administered intranasally, with 
1 hour between each application. Fifteen minutes prior to each application of medication, the 
nasal mucosa will be anesthetized with 100 ul of 1% lidocaine will be applied to each nasal 
cavity via MAD for all study participants. The lidocaine should not alter the nasal mucosa 
reaction to capsaicin; and is meant to anesthetize the area from the mild stinging of capsaicin. In 
fact, because lidocaine has a very mild stinging sensation at times; it can serve to mask the 
stinging one may get with intranasal capsaicin. Using the MAD, 100 μL of 1% ethanol in 0.9% 
saline solution (Group A) or 0.8 mL solution with (0.1mmol/l) of capsaicin in 1% ethanol in 
0.9% saline (Group B) will be delivered to each nasal cavity. On this day, they will not need to 
undergo optical rhinometry. Patients will fill out composite symptoms scores before and five 
minutes after 1st and 5th treatments. Patients who complete this portion of the experiment will 
receive $50 dollars in compensation as well as parking. 
Patients will then follow up 4 and 12 weeks after initiating treatment. At the 4 week and 
12 week follow-up appointments, subjects will undergo capsaicin challenge followed by ORM 
and composite symptom score of nasal symptoms will be reported. Patients who complete both 
follow up visits will receive $25 dollars in compensation as well as parking. 
 
 
Compensation: 


IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
In summary, patients that undergo the screening process and complete the skin prick 
testing and intranasal capsaicin challenge and ORM will be compensated $25 as well as parking 
validation. Patients that undergo the treatment will be compensated $50 plus parking for 
completing that day. Patients that complete the study and return 4 and 12 weeks post treatment, 
will be compensated $25 plus parking. 
 
Data and Safety Monitoring: 
Previous studies have shown that the concentration of capsaicin that will be used is 
generally well tolerated. 
Regarding the lidocaine, it is administered routinely in our clinic prior to nasal endoscopy 
and flexible laryngoscopy exams. Side effects can include minor stinging and burning when 
applied to the nose. Because it is an intranasal spray, there is a risk that patients will swallow it 
and may have difficulty swallowing for up to 45 minutes after application. We express to 
patients that they should avoid eating or drinking anything up to 45 minutes after the lidocaine 
application. 
Regarding skin prick testing, patients may have mild discomfort where the skin is 
pricked. They may have symptoms such as itching, a stuffy nose, red watery eyes, or a skin rash. 
Rarely, people can have anaphylaxis, but this usually only occurs with intradermal testing, which 
we will not be performing. If patients become short of breath, we do have oxygen available in 
the clinic. 
Patients will be educated to call the outpatient Otolaryngology clinic at the University of 
Texas Medical School at Houston if there are any adverse effects. 
 
Human Subjects: 
Participants will be sought from those presenting to the outpatient Otolaryngology clinic at the 
University of Texas Medical School at Houston. Patients included in the study will be between 
the ages of 18 and 70 with no history of sinonasal surgery, intranasal steroid use for more than 4 
weeks, intranasal or systemic antihistamine for 3 days, intranasal or systemic decongestants for 3 
days, chronic rhinosinusitis, inflammatory or granulomatous diseases, asthma, allergic rhinitis, 
immunocompromised state or radiation to the head and neck. 
 
This is a small study of only 22 subjects total and as addressed previously we anticipate 
screening 60 subjects in order to complete our enrollment. . Our practice consists of adult 
patients with a majority of who speak and read English. Therefore, it is unlikely to exclude a 
subject from the study because they do not speak or read English 
 
Statistical Analysis: 
Justification of sample size: 
Using Dr. Lambert’s paper (17) : his article showed the average maximum optical density in 
NAIR patients was 0.2 (SD 0.051), seen when using the 0.05 mM concentration of capsaicin 
during the capsaicin challenge and ORM. Healthy control subjects had a mean maximal OD 
change of 0.174 (SD 0.034). This was significant to p=0.01. Based on this data, 11 patients will 
need to be recruited to detect a significant post-treatment change. 
Student’s t-test will be used to compare the mean change in composite symptom scores 
pre and post-treatment in both groups. Student’s t-test will also be used to compare changes in 
maximal optical density in response to capsaicin challenge pre- and post-treatment in both 


IRB NUMBER: HSC-MS-14-0173 
IRB APPROVAL DATE: 11/18/2019 
 
groups. Statistical significance will result if p <0.05. The Spearman Rank Correlation will be 
used to analyze associations between composite symptom scores and changes in OD. 
 
Ethics: 
IRB approval will be sought from CPHS 
 
Data Handling and Record Keeping: In order to maintain confidentiality, a data sheet with 
patient’s names and data collected for the study (see data sheet) will be stored in a locked file 
cabinet within the department of Otorhinolaryngology. Access to data sheets in patient will be 
limited to co-investigators and research coordinator. Only de-identified data or collective data 
will be shared. 
 
Quality control and assurance: In order to confirm that the diagnosis of non-allergic irritant 
rhinitis is accurate and made in an unbiased manner, a history of rhinitic symptoms will be 
confirmed with objective skin testing. 
All datasheets will be recorded by PI and reviewed by at least one of the other 3 co- 
investigators to ensure accuracy in the recording of clinical data. 
 
Publication Plan: This study has been funded by the American Association of Otolaryngic 
Allergy (AAOA) Foundation Grant. Results from this study will be presented at a future AAOA 
national meeting and initial publication rights will be given to the International Forum of Allergy 
and Rhinology. 
All enrolled subjects will be notified of any publication resulting from this study, but these 
publications will present data on only the aggregate group. 
 
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