Trial Outcomes & Findings for Steroid Nasal Irrigation for Flavor Evaluation and Detection Study (NCT NCT02985515)

Last Updated: 2022-11-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

51 participants

Primary outcome timeframe

12 weeks

Results posted on

2022-11-04

Participant Flow

Adults 18 to 70 years of age with clinically diagnosed or self reported postviral olfactory loss of 3 months or longer were eligible to participate. For the control group, adults with normal smell function were eligible to participate.

PVOD participants first underwent 30-day trial period of budesonide nasal irrigation. If they did not experience improvement in their smell to the normal range as measured by UPSIT and Sniffin'Sticks, they continued budesonide nasal irrigation plus 12-weeks of smell intervention. Resting-state fMRI was obtained before and after smell intervention. For the participants in the Control Group, one time fs-MRI and questionnaire completion only.

Participant milestones

Participant milestones
Measure	Controls Healthy volunteers with normal smell function. Participants in the Control Group completed UPSIT, MRI, and Questionnaires one time and were finished with study participation.	Budesonide Nasal Irrigation 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.
Olfaction Testing STARTED	20	31
Olfaction Testing COMPLETED	20	23
Olfaction Testing NOT COMPLETED	0	8
Smell Training STARTED	0	23
Smell Training COMPLETED	0	23
Smell Training NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Controls Healthy volunteers with normal smell function. Participants in the Control Group completed UPSIT, MRI, and Questionnaires one time and were finished with study participation.	Budesonide Nasal Irrigation 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.
Olfaction Testing Lost to Follow-up	0	5
Olfaction Testing Protocol Violation	0	3

Baseline Characteristics

A total of 31 PVOD participants were in the Budesonide Nasal Irrigation group. Of the 31 participants, 23 participants remained after 8 were removed for protocol violations. The remaining 23 participants showed no improvement after the 30 days of budesonide nasal irrigation and therefore continued on the study and received 12 weeks of smell training. 20 participants in the Control Group.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 12 weeks

Population: Of the total 23 participants who completed smell training and rs-fMRI, 7 were excluded from analysis because of excessive artifact. Thus, the final study included a total of 16 participants. A set of 164 regions of interest(ROIs) from the CONN toolbox were used, supplemented with 23 ROIs determined by prior studies to be associated with olfactory processing. The CONN toolbox is an open source Matlab/SPM software that integrates pre-processing, display, and analysis of rs-fMRI data.

Outcome measures

Outcome measures
Measure	Smell Training n=187 Regions of interest Participants will first undergo a 30-day trial of budesonide nasal saline irrigation. If there is no subsequent improvement in olfaction, participants will undergo a 12-week smell training intervention. Smell training: Eligible participants will be provided with a "NeilMed" Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets. Participants will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. The contents of two capsules (0.5mg budesonide each) will be dissolved into "NeilMed" Sinus Rinse Regular Bottle along with the saline rinse. Both nasal cavities will be irrigated once daily for 30 days. Participants who do not have objective improvement in their olfaction after the trial of budesonide irrigation will have a baseline resting-state fMRI (rs-fMRI) and undergo 12 weeks of smell training. Smell training involves the participants smelling 4 vials of essential odors twice a day for 12 weeks. Following smell training, participants will have their smell ability re-evaluated and a second rs-fMRI performed.
Pre- and Post-intervention Difference in Functional Connectivity Before and After Smell Training.	5 Regions of interest

SECONDARY outcome

Timeframe: 30 days

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.

Outcome measures

Outcome measures
Measure	Smell Training n=16 Participants Participants will first undergo a 30-day trial of budesonide nasal saline irrigation. If there is no subsequent improvement in olfaction, participants will undergo a 12-week smell training intervention. Smell training: Eligible participants will be provided with a "NeilMed" Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets. Participants will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. The contents of two capsules (0.5mg budesonide each) will be dissolved into "NeilMed" Sinus Rinse Regular Bottle along with the saline rinse. Both nasal cavities will be irrigated once daily for 30 days. Participants who do not have objective improvement in their olfaction after the trial of budesonide irrigation will have a baseline resting-state fMRI (rs-fMRI) and undergo 12 weeks of smell training. Smell training involves the participants smelling 4 vials of essential odors twice a day for 12 weeks. Following smell training, participants will have their smell ability re-evaluated and a second rs-fMRI performed.
Pre- and Post-intervention Difference in Smell Testing Before and After Budesonide Treatment TDI	17.5 units on a scale Interval 7.0 to 27.2
Pre- and Post-intervention Difference in Smell Testing Before and After Budesonide Treatment UPSIT	19.5 units on a scale Interval 5.0 to 40.0

SECONDARY outcome

Timeframe: 12 weeks

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.

Outcome measures

Outcome measures
Measure	Smell Training n=16 Participants Participants will first undergo a 30-day trial of budesonide nasal saline irrigation. If there is no subsequent improvement in olfaction, participants will undergo a 12-week smell training intervention. Smell training: Eligible participants will be provided with a "NeilMed" Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets. Participants will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. The contents of two capsules (0.5mg budesonide each) will be dissolved into "NeilMed" Sinus Rinse Regular Bottle along with the saline rinse. Both nasal cavities will be irrigated once daily for 30 days. Participants who do not have objective improvement in their olfaction after the trial of budesonide irrigation will have a baseline resting-state fMRI (rs-fMRI) and undergo 12 weeks of smell training. Smell training involves the participants smelling 4 vials of essential odors twice a day for 12 weeks. Following smell training, participants will have their smell ability re-evaluated and a second rs-fMRI performed.
Subjective Response to Smell Training Intervention	23.8 units on a scale Interval 9.0 to 83.8

SECONDARY outcome

Timeframe: 1 week

Population: A set of 164 regions of interest (ROIs) from the CONN toolbox were used, supplemented with 23 ROIs determined by prior studies to be associated with olfactory processing.

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.

Outcome measures

Outcome measures
Measure	Smell Training n=187 Regions of interest Participants will first undergo a 30-day trial of budesonide nasal saline irrigation. If there is no subsequent improvement in olfaction, participants will undergo a 12-week smell training intervention. Smell training: Eligible participants will be provided with a "NeilMed" Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets. Participants will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. The contents of two capsules (0.5mg budesonide each) will be dissolved into "NeilMed" Sinus Rinse Regular Bottle along with the saline rinse. Both nasal cavities will be irrigated once daily for 30 days. Participants who do not have objective improvement in their olfaction after the trial of budesonide irrigation will have a baseline resting-state fMRI (rs-fMRI) and undergo 12 weeks of smell training. Smell training involves the participants smelling 4 vials of essential odors twice a day for 12 weeks. Following smell training, participants will have their smell ability re-evaluated and a second rs-fMRI performed.
Comparison of Olfactory Network in Healthy Controls to Study Participants	13 Regions of interest

SECONDARY outcome

Timeframe: 12 weeks

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.

Outcome measures

Outcome measures
Measure	Smell Training n=16 Participants Participants will first undergo a 30-day trial of budesonide nasal saline irrigation. If there is no subsequent improvement in olfaction, participants will undergo a 12-week smell training intervention. Smell training: Eligible participants will be provided with a "NeilMed" Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets. Participants will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. The contents of two capsules (0.5mg budesonide each) will be dissolved into "NeilMed" Sinus Rinse Regular Bottle along with the saline rinse. Both nasal cavities will be irrigated once daily for 30 days. Participants who do not have objective improvement in their olfaction after the trial of budesonide irrigation will have a baseline resting-state fMRI (rs-fMRI) and undergo 12 weeks of smell training. Smell training involves the participants smelling 4 vials of essential odors twice a day for 12 weeks. Following smell training, participants will have their smell ability re-evaluated and a second rs-fMRI performed.
Pre- and Post-intervention Difference in Smell Testing Before and After Smell Training UPSIT	19 units on a scale Interval 9.0 to 40.0
Pre- and Post-intervention Difference in Smell Testing Before and After Smell Training TDI	18.3 units on a scale Interval 7.0 to 34.5

SECONDARY outcome

Timeframe: 12 weeks

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.

Outcome measures

Outcome measures
Measure	Smell Training n=16 Participants Participants will first undergo a 30-day trial of budesonide nasal saline irrigation. If there is no subsequent improvement in olfaction, participants will undergo a 12-week smell training intervention. Smell training: Eligible participants will be provided with a "NeilMed" Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets. Participants will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. The contents of two capsules (0.5mg budesonide each) will be dissolved into "NeilMed" Sinus Rinse Regular Bottle along with the saline rinse. Both nasal cavities will be irrigated once daily for 30 days. Participants who do not have objective improvement in their olfaction after the trial of budesonide irrigation will have a baseline resting-state fMRI (rs-fMRI) and undergo 12 weeks of smell training. Smell training involves the participants smelling 4 vials of essential odors twice a day for 12 weeks. Following smell training, participants will have their smell ability re-evaluated and a second rs-fMRI performed.
Pre and Post Difference in QOD-NS After Smell Training	7.4 units on a scale Interval 0.0 to 17.1

Adverse Events

Control Group

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Budesonide Nasal Irrigation

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Control Group n=20 participants at risk 20 participants sex and age matched (+/- 5 years) to participants with PVOD with normal smell as determined by UPSIT were recruited for baseline neuroimaging.	Budesonide Nasal Irrigation n=31 participants at risk Adults 18 to 70 years of age with clinically diagnosed or self-reported postviral olfactory loss of 3 months underwent 30-day trial of budesonide nasal irrigation. If they improved, study participation ended. If they had no improvement in sense of smell after a 30-day trial of budesonide nasal irrigation, they then underwent 12-weeks of smell training intervention. All participants who underwent the 12-weeks of smell training intervention are included this adverse event group. Adverse Events were not collected separately in the Smell Training portion of the study from the Budesonide Nasal Irrigation but instead collected as a whole.
Nervous system disorders Cavernoma	10.0% 2/20 • Number of events 2 • Up through 13 months \# who underwent budesonide nasal irrigation at risk for serious adverse events:31; All participants who underwent the 12-weeks of smell training are included because all underwent 30-day trial of budesonide nasal irrigation. If improved, participation ended.If no improvement, they underwent 12-weeks of smell training intervention. # of controls at risk for serious adverse events:20; Adverse Events were not collected separately in the Smell Training portion from the Budesonide Nasal Irrigation.	0.00% 0/31 • Up through 13 months \# who underwent budesonide nasal irrigation at risk for serious adverse events:31; All participants who underwent the 12-weeks of smell training are included because all underwent 30-day trial of budesonide nasal irrigation. If improved, participation ended.If no improvement, they underwent 12-weeks of smell training intervention. # of controls at risk for serious adverse events:20; Adverse Events were not collected separately in the Smell Training portion from the Budesonide Nasal Irrigation.
Nervous system disorders pleomorphic adenoma	5.0% 1/20 • Number of events 1 • Up through 13 months \# who underwent budesonide nasal irrigation at risk for serious adverse events:31; All participants who underwent the 12-weeks of smell training are included because all underwent 30-day trial of budesonide nasal irrigation. If improved, participation ended.If no improvement, they underwent 12-weeks of smell training intervention. # of controls at risk for serious adverse events:20; Adverse Events were not collected separately in the Smell Training portion from the Budesonide Nasal Irrigation.	0.00% 0/31 • Up through 13 months \# who underwent budesonide nasal irrigation at risk for serious adverse events:31; All participants who underwent the 12-weeks of smell training are included because all underwent 30-day trial of budesonide nasal irrigation. If improved, participation ended.If no improvement, they underwent 12-weeks of smell training intervention. # of controls at risk for serious adverse events:20; Adverse Events were not collected separately in the Smell Training portion from the Budesonide Nasal Irrigation.
Nervous system disorders extra-axial meningiomas	0.00% 0/20 • Up through 13 months \# who underwent budesonide nasal irrigation at risk for serious adverse events:31; All participants who underwent the 12-weeks of smell training are included because all underwent 30-day trial of budesonide nasal irrigation. If improved, participation ended.If no improvement, they underwent 12-weeks of smell training intervention. # of controls at risk for serious adverse events:20; Adverse Events were not collected separately in the Smell Training portion from the Budesonide Nasal Irrigation.	6.5% 2/31 • Number of events 2 • Up through 13 months \# who underwent budesonide nasal irrigation at risk for serious adverse events:31; All participants who underwent the 12-weeks of smell training are included because all underwent 30-day trial of budesonide nasal irrigation. If improved, participation ended.If no improvement, they underwent 12-weeks of smell training intervention. # of controls at risk for serious adverse events:20; Adverse Events were not collected separately in the Smell Training portion from the Budesonide Nasal Irrigation.

Additional Information

Pawina JIramongkolchai, MD

Washington University in St. Louis

Phone: 314-393-2455

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place