Steroid Nasal Irrigation for Flavor Evaluation and Detection Study

Study Overview
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Brief Summary
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The purpose of this research study is to examine the efficacy of a 12-week smell training intervention for participants with olfactory dysfunction following an infection of the upper respiratory tract.

Detailed Description
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Olfactory dysfunction affects up to fifteen percent of the general population and can cause significant psychosocial distress including decreased appetite, reduced self-hygiene, and mood disturbances. This study aims to study the efficacy of smell training for patients with olfactory dysfunction following a viral upper respiratory tract infection. Eligible participants will complete a 30-day course of budesonide nasal saline irrigation. Participants who do not show improvement in their olfaction based on composite smell and taste tests will be eligible to receive a baseline resting-state fMRI (rs-fMRI) and complete a 12-week smell training intervention program. Smell training involves participants smelling 4 odors (phenyl ethyl alcohol, eucalyptus, lemon, and eugenol) twice a day for 12 weeks. Following completion of smell training, participants will undergo repeat smell and taste tests as well as rs-fMRI to ascertain the efficacy of smell training.

Official Title
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Steroid Nasal Irrigation for Flavor Evaluation and Detection (SNIFFED) Study

Conditions
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Olfactory Disorder

Intervention / Treatment
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* Behavioral: Smell training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 Anosmia or hyposmia (UPSIT <34 (male), UPSIT <34 (female); Sniffin' Sticks threshold below 5.5) Exclusion Criteria: Inability to understand English Current smoker or history of smoking within the past 6 months Current nasal polyps Exposure to head and or/neck radiation Exposure to chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective cohort, pre- and post-intervention study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Budesonide Nasal Irrigation<br>30-day run-in course of budesonide nasal irrigation. 1-month supply of budesonide capsules, an 8-oz sinus rinse bottle, and a 1-month supply of commercially prepared isotonic salt packets. Participants were instructed to dissolve 2 budesonide capsules (0.5mg per capsule) into the sinus rinse bottle along with the saline mixture and then irrigate both nasal cavities once daily. | |
| Experimental: Budesonide Nasal Irrigation + Smell Training<br>Budesonide nasal irrigation + smell training for 12 weeks | Behavioral: Smell training<br>* Participants will be provided with 4 vials of essential odors. Participants will sniff each scent for 20-30 seconds, twice daily, for 12 weeks. The participant will take 30 seconds of rest between each scent. All participants will undergo this smell training regimen for 12 weeks.<br>* Other names: Olfactory Training;|
| No Intervention: Controls<br>Baseline olfaction testing and rs-fMRI | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre- and Post-intervention Difference in Functional Connectivity Before and After Smell Training. | Baseline and post-intervention connectivity within and between regions of interest in the olfactory and olfactory related networks using resting state fMRI will be obtained. Resting-state connectivity was analyzed using the CONN toolbox version 18b (https://web.conn-toolbox.org/) and SPM12, version 7487 (Wellcome Trust Centre for Neuroimaging). Functional connectivity values (Fisher z-transformed Pearson correlation coefficients) were compared using a paired, 2-tailed t test and corrected for multiple comparisons. p<0.05 was considered to be significant. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre- and Post-intervention Difference in Smell Testing Before and After Budesonide Treatment | Objective pre- and post-intervention differences of participant performance on the UPSIT and Sniffin Sticks tests before and after budesonide saline nasal irrigation. University of Pennsylvania Identification Test (UPSIT) consists of 4 odor-impregnated booklets that participants scratch and sniff to identify various odors, and scores account for differences in sex. Hyposmia is defined as a score of 19 to 34 for females and 19 to 33 for males. Anosmia for either sex is defined as a score below 18. Possible scores range from 0 to 40 with higher scores indicating better sense of smell. Sniffin' Sticks are odor-encapsulated markers that are used to measure odor detection threshold, discrimination, and identification (TDI). Normosmia is defined as a TDI score >30.5. An increase by 5.5 points or more from baseline is considered meaningful improvement. Possible scores range from 1 to 48 with higher values indicating better sense of smell. | 30 days | 
| Subjective Response to Smell Training Intervention | Participants subjective sense of smell following intervention is measured using a visual analogue scale from 0 to 100 with 0 representing no sense of smell and 100 representing best possible sense of smell. | 12 weeks | 
| Comparison of Olfactory Network in Healthy Controls to Study Participants | Baseline functional connectivity within and between the olfactory and associated networks of healthy controls will be compared to that of study participants prior to smell intervention treatment as measured by rs-fMRI.Resting-state connectivity was analyzed using the CONN toolbox version 18b (https://web.conn-toolbox.org/) and SPM12, version 7487 (Wellcome Trust Centre for Neuroimaging). Functional connectivity values (Fisher z-transformed Pearson correlation coefficients) were compared using a paired, 2-tailed t test and corrected for multiple comparisons . P < .05 was considered statistically significant. | 1 week | 
| Pre- and Post-intervention Difference in Smell Testing Before and After Smell Training | Objective pre- and post-intervention differences of participant performance on the UPSIT and Sniffin Sticks tests before and after budesonide saline nasal irrigation. University of Pennsylvania Identification Test (UPSIT) consists of 4 odor-impregnated booklets that participants scratch and sniff to identify various odors, and scores account for differences in sex. Hyposmia is defined as a score of 19 to 34 for females and 19 to 33 for males. Anosmia for either sex is defined as a score below 18. Possible scores range from 0 to 40 with higher scores representing better sense of smell. Sniffin' Sticks are odor-encapsulated markers that are used to measure odor detection threshold, discrimination, and identification (TDI). Normosmia is defined as a TDI score >30.5. An increase by 5.5 points or more from baseline is considered meaningful improvement. Possible scores range from 1 to 48 with higher values indicating better sense of smell. | 12 weeks | 
| Pre and Post Difference in QOD-NS After Smell Training | The QOD-NS is a validated 17-item questionnaire that pertains to olfactory-specific quality of life domains adversely impacted by olfactory dysfunction and is inversely scored (maximum score of 51), with higher scores reflective of more impaired quality of life. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anosmia, Hyposmia, Intranasal Steroid Irrigation, Olfactory Neuroplasticity, Olfactory training