Effects of Radiofrequency Ablation of Posterior Nasal Nerves on Inflammatory Cytokines, Peak Nasal Inspiratory Flow, and Nasal Blood Flow in Patients With Chronic Rhinitis
Phase: NA
Conditions: Chronic Rhinitis
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-MS-22-0899 
IRB APPROVAL DATE: 01/19/2023 
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Effects of Radiofrequency Ablation of Posterior Nasal Nerves on Inflammatory 
Cytokines, Peak Nasal Inspiratory Flow, and Nasal Blood Flow in Patients with 
Chronic Rhinitis 
 
NCT05648565 
 
Version Date: 1/19/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB NUMBER: HSC-MS-22-0899 
IRB APPROVAL DATE: 01/19/2023 
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Protocol Title: 
Effects of Radiofrequency Ablation of Posterior Nasal Nerves on 
Inflammatory Cytokines, Peak Nasal Inspiratory Flow, and Nasal 
Blood Flow in Patients with Chronic Rhinitis 
Principal 
Investigator: 
Dr. David Z. Allen 
Co-Investigators: 
Dr. Amber Luong, Dr. William Yao, Dr. Martin Citardi, Dr. Denna 
Zebda 
Study Coordinator: 
Dr. David Z. Allen 
 
Population: 
Will be enrolling at least 36 patients of good health with chronic 
rhinitis. Patients will be eligible for intervention if they have chronic 
rhinitis symptoms for at least 6 months and have failed medical 
treatment. Patients will be enrolled at the Texas Medical Center in 
Houston, Texas. 
Number of Sites: 
Single site / UT Houston is the only site 
 
Study Duration: 
Twelve Months 
 
Subject Duration: 
14 weeks, 28 weeks if patients decide to participate in the optional last 
patient visit 
 
General Information 
Patients with chronic rhinitis (CR) often fail medical management. In-office radiofrequency 
ablation (RFA) of the posterior nasal nerve (PNN) has been established as an effective therapy 
for CR. However, understanding the objective response, such as nasal patency as determined by 
peak nasal inspiratory flow (PNIF) and changes to type 2 cytokine profiles, to this treatment has 
yet to be elucidated. We will be performing RFA of the PNN and evaluating the change in 
PNIF, patient symptom scores and cytokine changes thereafter in patients with CR. 
 
Background Information 
CR is inflammation of the nasal mucosa that leads to symptoms such as sneezing, congestion, 
and post-nasal drip that is separated by an allergic response - allergic rhinitis and non-allergic 
rhinitis (NAR). AR is an IgE-mediated inflammation of the nasal mucosa while NAR is non-IgE- 
mediated and has multiple etiologies including vasomotor, hormonal, and occupational among 
others. Overall, the condition affects 40 million people in the US annually and is a contributor to 
healthcare utilization and morbidity. Research has illustrated that contributors to AR are 
cytokines such as Interleukin (IL-) 3, 4, 5 whom stimulate immunoglobulin production and 
recruit inflammatory cells such as mast cells and eosinophils. In NAR, the pathophysiology is 
less clear and may be associated with irregularities of neural function. Regardless, AR treatment 
consists of a steroid and/or antihistamine spray, saline irrigations, and antihistamines. For NAR, 

IRB NUMBER: HSC-MS-22-0899 
IRB APPROVAL DATE: 01/19/2023 
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anti-cholinergic sprays in addition to broad-based therapies such as steroid/antihistamine 
sprays are utilized. In both, there is a high rate of persistent symptoms, treatment failure, and 
prolonged medication administration, thus forcing patients to seek procedural interventions. 
Historically, options have included septoplasty, turbinate reduction, vidian neurectomy and/or 
posterior nasal nerve (PNN) neurectomy. However, these procedures incur risks and are 
typically performed in the operating room. Recently, office-based procedures have been 
introduced to address symptoms of nasal congestion and drainage. Temperature-controlled 
radiofrequency ablation (RFA) is a safe in-office procedure that has been shown to decrease 
symptoms. However, no data has been reported on effects of RFA on objective variables 
associated with rhinitis. Peak nasal inspiratory flow (PNIF) is an objective outcome for nasal 
congestion which is a simple, cost-effective, and reliable measure that is performed in-office. To 
our knowledge, PNIF has not been studied as a measure of the effectiveness of RFA of PNN. 
We believe that this procedure will improve nasal patency and thus PNIF. Finally, RFA of PNN 
has been proposed as a therapeutic option for both AR and NAR, as it has shown to be effective 
in all types of chronic rhinitis, possibly by changing the underlying cytokine profile in the 
disease. For instance, type 2 cytokines are elevated in AR and are critical in its pathophysiology. 
We propose that the positive symptom effects of RFA in CR patients may be linked to changes 
in Type 2 cytokines and we seek to measure those levels. We will then attempt to correlate or 
understand the relationship that these objective values have with subjective patient scores that 
are well established in the literature such as reflective total nasal symptom score (rTNSS) and 
nasal obstruction symptom evaluation (NOSE) values. 
Objectives 
In summary, the primary outcome of this project is to determine how RFA of the PNN affects 
underlying cytokine profiles in addition to peak nasal inspiratory flow levels. The secondary 
outcomes of this study will be to assess how RFA of the PNN changes subjective symptom 
scores such as rTNSS and NOSE. 
Study Design 
This will be a prospective, single-arm single institution study with enrollment at the Texas 
Sinus Institute at The University of Texas Health Science Center at Houston. The patients will 
be enrolled through a 12-month time frame. Each patient will have a required 14-week 
participation window with an optional visit at 28 weeks as well. We will be assessing the 
objective and subjective response of RFA of the PNN in patients with rhinitis. At each post- 
procedure visit including the procedure visit, we will be assessing side effects and adverse 
events of the treatment. The primary outcome of this project is to determine how RFA of the 
PNN affects underlying cytokine profiles in addition to peak nasal inspiratory flow levels, 
which will be determined at weeks 0 and 12 for cytokine changes and weeks 0, 4, 12 and an 
optional 26 weeks for PNIF. The secondary outcomes of this study will be to assess how RFA of 
the PNN changes subjective symptom scores such as rTNSS and NOSE and this will be assessed 
at weeks 0, 4, 12 and an optional 26 weeks. 
Study Population 
Patients between the ages of 18-80 will be eligible for intervention if they have chronic rhinitis 
symptoms for at least 6 months (rhinorrhea, congestion, post-nasal drip), poor response to 

IRB NUMBER: HSC-MS-22-0899 
IRB APPROVAL DATE: 01/19/2023 
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medical management that was attempted for at least 4 weeks, a rTNSS score ≥6, as well as ≥2 for 
rhinorrhea, and ≥1 for congestion. Exclusion criteria consists of active sinusitis, rhinitis 
medicamentosa, recurrent and ongoing epistaxis, immunodeficiency as defined by an illness or 
a history of sinus surgery. We will perform a query within the electronic medical record to 
assist in finding patients with chronic rhinitis. 
 
The following ICD-10 codes will be used: 
 
- 
J30.9 Allergic Rhinitis 
- 
J30 Vasomotor rhinitis 
- 
R09.82 Post-nasal drip/Chronic Rhinitis 
- 
J34.89 Rhinorrhea 
- 
J30.81 Animal Dander rhinitis 
- 
J30.89 Dust rhinitis 
- 
J30.5 Food induced rhinitis 
- 
J31 Atrophic rhinitis 
Then we will reach out to them and offer them participation in the study. 
Study Procedures 
There will be a total of four required visits with an optional fifth visit. At the first visit, enrolled 
participates will be screened and stopped on all intranasal corticosteroids. The total clinic 
appointment should not exceed 30 minutes. At this visit, we will be obtaining all relevant 
demographic information for analysis such as age, gender, years of rhinitis symptoms, medical 
co-morbidities, types of medical management that had been trialed and for how long, history of 
other allergic symptoms, and specific allergic triggers or prior allergy test results. We will 
collect this through the electronic medical record and then collate and save this data on an 
encrypted hard drive. At the second visit (at least two weeks from the first visit), we will teach 
and train participants to perform PNIF for which we will take the highest of three repeated 
values, we will also collect rTNSS and NOSE values in addition to nasal secretions prior to the 
procedure. The patient will fill the symptom score evaluations out on handouts, and we will 
tabulate the responses on an encrypted drive. We will collect the PNIF values on the electronic 
medical record and then record and save them on an encrypted hard drive. Our laboratory has 
established a protocol utilizing a White Blood Cell Isolation Medium called Leukosorb (Pall 
Corporation, New York) for nasal secretions. The Leukosorb paper is an efficient way to collect 
nasal secretions for cytokine analysis. The 1 x 1 cm paper will be placed over the posterior 
aspect of the inferior turbinate near the treatment site under endoscopic visualization. The 
paper is left in place for 5 minutes and then retrieved into an Eppendorf tube on ice. The paper 
will be stored at -80 until processed. To process, the paper collected secretions are eluted from 
the Leukosorb paper by centrifugation and stored at -20C for analysis by Biolegend. For 
confidentiality, each patient will be assigned a study identification number and all samples 
collected will be labeled with a study identification number. The document key correlating 
patient to their study identification number will be stored in a password protected document on 
UT server. For the treatments, we will be using Neurent Medical’s Neuromark™ system 

IRB NUMBER: HSC-MS-22-0899 
IRB APPROVAL DATE: 01/19/2023 
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(Neurent, Ireland). This device has been approved by the FDA for treatment of chronic rhinitis. 
The NEUROMARK device is an in-office, disposable bipolar RFA device with a treatment tip 
consisting of micro electrodes which delivers RF energy while monitoring appropriate tissue 
contact to maximize delivery to posterior nasal nerve and its variable branching. After topical 
anesthesia consisting of oxymetazoline and 1% lido followed by 4% lidocaine, the device will be 
placed in the posterior inferior turbinate under endoscopic visualization. The device will be 
activated per manufacturer’s instructions. After the procedure we will allow the patient to 
recover appropriately and ask for any adverse events or side effects at that time. We will detail 
these adverse events in the electronic medical record and record them in the encrypted hard 
drive. The second visit should take around 45-90 minutes. There will be subsequent visits at 
week four post procedure and week twelve post procedure. At week four we will be assessing 
side effects and adverse events in addition to obtaining rTNSS, NOSE, and PNIF values. This 
visit should not take more than 20-30 minutes. At week 12 post-procedure we will be obtaining 
rTNSS, NOSE, PNIF and nasal secretions for cytokine analysis. This visit should take around 30- 
45 minutes at most. The last optional visit, week 26 post-procedure, will be identical to week 4’s 
visit, and should last no more than 30 minutes. The total clinic time required will be 150 
minutes with an optional extra 30 (180 minutes) should patients want to participate in the final 
clinic visit. After week 12, statistical analysis and comparative analytics will be initiated. 
 
Data and Safety Monitoring 
Adverse events are not expected however should they occur patients will report them to the PI 
of the study. Any Adverse or unanticipated events will be reviewed monthly during regularly 
monthly meeting involving Drs. Luong, Citardi and Yao. The adverse events will be 
adjudicated by the committee. A log of these events will be kept. Any adverse event resulting 
from the device will be reported to the company. 
 
Statistics 
This study will be a prospective analysis. The primary endpoint is the change in PNIF from 
baseline after RFN treatment of the PNN at 12 weeks. Prior literature has shown that treatment 
of rhinitis can lead to an increase of PNIF in variable amounts depending on baseline. Literature 
suggests an average increase of PNIF to be around 25-35 L/min after treatment, with a standard 
deviation (SD) of approximately 30 L/min. With an average expected change of 30, SD of 30, and 
80% power at alpha of 0.05, the minimum sample size should be 32. Assuming a 10% dropout 
rate, we seek to enroll 36 eligible subjects. We will also perform analyses of rTNSS and NOSE 
scores. As has been published, a patient will be considered a “responder” if they have at least 
30% reduction of rTNSS at 12 weeks and ≥1 NOSE class improvement or a reduction in NOSE at 
least 20% from pre-treatment. Additionally, the minimum clinically important difference 
(MCID) for the RQLQ(S) is established at ≥0.5 points and 20 for PNIF. We will be performing 
statistical analysis after each post-procedure visit, but the primary objective will be evaluation 
of the PNIF and cytokine changes after week 12. However we will also assess how PNIF scores 
change at weeks 4 and 26 in addition to week 12. The secondary outcomes will be to assess how 
RFA of the PNN changes subjective symptom scores such as rTNSS and NOSE at weeks 4, 12, 

IRB NUMBER: HSC-MS-22-0899 
IRB APPROVAL DATE: 01/19/2023 
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and 26. Comparative analytics will be performed on all groups. Paired t-tests, Wilcoxon-Mann t- 
tests, chi-squared tests and ANOVA analysis will be used. Criteria for termination of the study 
could be poor recruitment in which the study could not be completed within 3 years. 
Ethics 
We will be obtaining a waiver of consent for every patient. Each patient will have a unique 
identifier without any identifiable medical information. There is a risk of data breech however 
all information will be stored on a HIPPA compliant database on a University of Texas server 
that will be de-identified. The patient information will be kept using a linking log and a unique 
patient identifier for each patient. All data will be saved on encrypted University of Texas 
computers using the HIPPA compliant database. Patient information and data will be stored for 
three years. 
Data handling and record keeping 
Only collaborators of this investigation will have access to the patient data and information. We 
will be ensuring that all patients have a unique identifier without any medical information. All 
data will be saved on an encrypted hard drive and encrypted data sheets. Human subjects will 
not be identifiable. 
 
Quality control and assurance 
An electronic medical record will be kept for each study visit. Data documents will be 
compared to electronic medical record to confirm accuracy of collected data. Audits of the 
source data will be performed by the faculty mentor on a minimum of annual basis. Source data 
will be audited by at least two members of the research team after each study visit. 
 
Publication Plan 
Findings will initially be presented at American Academy of Otolaryngic Allergy conference. 
Thereafter, we will seek to publish our results at a high-impact, and clinically relevant, journal.