Treatment of Pediatric Patients That Lost Sense of Smell Due to COVID-19

Study Overview
=================
Brief Summary
-----------------
This research study is a randomized controlled trial in pediatric and young adult patients who have lost their sense of smell due to COVID-19 viral infection. The goals are: to learn more about the effects of smell retraining therapy on smell loss following COVID-19 and to determine if budesonide-saline irrigations make smell retraining therapy more effective.

Detailed Description
-----------------
Researchers will screen all potentially eligible patients that have 'loss of smell' as their reason for visit at UPMC Children's Hospital of Pittsburgh Division of Pediatric Otolaryngology. At the initial consult appointment at the Division of Pediatric Otolaryngology, listed study team members will perform a smell identification test called the UPSIT (University of Pennsylvania Smell Identification Test) and give the SNOT-22 (Sino-Nasal Outcome Test-22) survey. The UPSIT is a 40-item scratch and sniff test with a four-choice multiple choice question on each of the 10 pages in the booklet. Indication of smell loss can be determined - anosmia (total loss) and mild, moderate, or severe microsomia and a detection for malingering. The SNOT-22 is a 22 question survey that asks about symptoms and social/emotional consequences of a nasal disorder. The survey is on a 6 point scale - No problem (0), very mild problem (1), mild or slight problem (2), moderate problem (3), severe problem (4), and problem as bad as it can be (5). A randomized clinical trial will be performed with two arms for those that have lost their sense of smell for at least 8 weeks: 1) smell retraining for 8 weeks 2) smell retraining + Budesonide irrigations for 8 weeks. Smell retraining consists of choosing 4 scents each week and smelling each item for 15 seconds very close to the nose once a day. Budesonide irrigations will be done once a day by pouring 0.5mg/2ml of Budesonide into a irrigation bottle with saline and irrigating the nose. Participants may do the therapies at any point during the day. Children and young adults ages 6 to 21 will be enrolled with 30 children block randomized in each arm, in which up to 10 children in each arm will be those who did not have a positive COVID-19 antigen test or confirmed COVID-19 by history. COVID-19 testing will be used for randomization purposes, but will not be limited to testing due to the inclusion of confirmation by history. Two groups of subjects for study inclusion: Group 1: COVID-19 by clinical history or lab testing (n=40 (20 randomized to each group)) Those with COVID-19 confirmation by clinical history may not have had a COVID-19 positive test. Group 2: Those that did not have COVID-19 by clinical history or lab testing (n=20 (10 randomized to each group)) These subjects may have had a negative COVID-19 test or no clinical history of COVID-19. Each child, with the help of their parents, will do the assigned therapy and fill out a daily Smell Diary. The child will pick 4 scents each week to perform the smell retraining each day that week. The child or parent will check mark every day that the 4 scents were smelled. The scents do not have to be new each week. Once a week the child will rate their loss of smell on a scale from 0 (no loss) to 10 (total loss). Researchers will check in with the parent or participant on weeks 3, 5, and after the 8 week period. Families will return the Smell Diary at their standard of care follow-up appointment at 8 weeks (range 8 to 12 weeks). The UPSIT and the SNOT-22 will be given at the follow-up appointment. If the participants' sense of smell did not return to baseline at the follow-up, they will be asked to return at 6 months after the initial consult. If the participants' sense of smell has still not returned at the 6 month appointment, they will be asked to follow-up at 1 year after the initial consult. The UPSIT and SNOT-22 will be given at each of these appointments. If smell was not a baseline at 8 weeks, listed investigators will call the subject or subjects' parents at 6 months and 1 year after the initial appointment to check-in and for a reminder to schedule a follow-up appointment. If participants do not have an 8-week follow-up visit, they may be mailed an UPSIT to complete at home and return by mail. They may also complete the SNOT-22 by mail or phone, and they may return the smell diary by email. If patients were initially randomized to the smell retraining only, after the initial 8-12 weeks of therapy they may be prescribed budesonide as part of standard of care to maximize medical management as needed. We will invite participants to fill out a new smell diary during this time and we will collect any data available from the smell diary, UPSIT, and SNOT-22 at their standard of care visit after 8-12 weeks of budesonide irrigation. Patients who have already completed more than 12 weeks of smell retraining will not be included in this arm; although budesonide may be prescribed based on physician discretion, data will not be collected following budesonide treatment.

Official Title
-----------------
Prospective Randomized Study of the Treatment of Pediatric Patients That Lost Sense of Smell Due to COVID-19

Conditions
-----------------
Dysosmia, Anosmia, Covid19

Intervention / Treatment
-----------------
* Other: Smell Retraining
* Drug: Budesonide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects ages 6 to 21 who have loss of smell (anosmia) or dysosmia (disordered smell perception) and thought to have occurred due to COVID-19. Subjects who are able to complete the smell test (UPSIT), self-report their loss of smell, and do the assigned daily therapy. Exclusion Criteria: Duration of anosmia or dysosmia <60 days Previous smell retraining Prior interventions for loss of smell (excluding those on Flonase and Azelastine) Contraindications for nasal budesonide treatment, as determined by the treating physician Active cigarette smoker or use of vapes Previous head trauma Congenital anosmia History of brain tumor Neurocognitive disorders Multiple sclerosis Seizure disorder Cystic fibrosis Primary Ciliary Dyskinesia History of nasal polyps Inability to self-report

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Smell Retraining Only<br>Participants will undergo smell retraining for 8 weeks. Each week, participants will choose 4 scents. They will smell each item for 15 seconds very close to the nose once a day. | Other: Smell Retraining<br>* Smell practice with household scented items<br>* Other names: Olfactory Retraining;|
| Experimental: Smell Retraining + Budesonide<br>Participants will undergo smell retraining as described above. They will also complete budesonide irrigations once a day by pouring 0.5mg/2ml of budesonide into a irrigation bottle with saline and irrigating the nose. | Other: Smell Retraining<br>* Smell practice with household scented items<br>* Other names: Olfactory Retraining;Drug: Budesonide<br>* Nasal irrigation with liquid steroid<br>* Other names: Nasal Glucocorticoid Irrigation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline to first follow-up | Change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline at the initial consult appointment to the first follow-up appointment at 8 weeks (range 8 to 12 weeks). The UPSIT is a smell identification test and is a 40-item scratch and sniff test with a four-choice multiple choice question on each of the 10 pages in the booklet. Indication of smell loss can be determined - anosmia (total loss) and mild, moderate, or severe microsomia and a detection for malingering. The minimum possible score is a 0 and the maximum is a 40. A higher score indicates better smell/outcome. | Before and after 8-12 weeks of smell retraining | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sino-nasal Outcome Test-22 (SNOT-22) score from baseline to first follow-up | Change in Sino-nasal Outcome Test-22 (SNOT-22) score from baseline at the initial consult appointment to the first follow-up appointment at 8 weeks (range 8 to 12 weeks). The SNOT-22 is a 22 question survey that asks about symptoms and social/emotional consequences of a nasal disorder. The survey is on a 6 point scale - No problem (0), very mild problem (1), mild or slight problem (2), moderate problem (3), severe problem (4), and problem as bad as it can be (5). The minimum possible score is 0 and the maximum is 110. A higher score indicates more sino-nasal symptoms/worse outcome. | Before and after 8-12 weeks of smell retraining | 
| Change in loss of smell question score from baseline to first follow-up | Change in loss of smell on a 0-10 scale from baseline at the initial consult appointment to the first follow-up appointment at 8 weeks (range 8 to 12 weeks). Subjects are asked to rate the symptom severity of loss of smell from 0 (no loss) to 10 (total loss). A higher score indicates worse smell/outcome. | Before and after 8-12 weeks of smell retraining | 
| Change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline to 6 month follow-up | Change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline at the initial consult appointment to the 6 month follow-up appointment. The minimum possible score is a 0 and the maximum is a 40. A higher score indicates better smell/outcome. | Baseline and 6 months after initial consult appointment | 
| Change in Sino-nasal Outcome Test-22 (SNOT-22) score from baseline to 6 month follow-up | Change in Sino-nasal Outcome Test-22 (SNOT-22) score from baseline at the initial consult appointment to the 6 month follow-up appointment. The minimum possible score is 0 and the maximum is 110. A higher score indicates more sino-nasal symptoms/worse outcome. | Baseline and 6 months after initial consult appointment | 
| Change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline to 12 month follow-up | Change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline at the initial consult appointment to the 12 month follow-up appointment. The minimum possible score is a 0 and the maximum is a 40. A higher score indicates better smell/outcome. | Baseline and 12 months after initial consult appointment | 
| Change in Sino-nasal Outcome Test-22 (SNOT-22) score from baseline to 12 month follow-up | Change in Sino-nasal Outcome Test-22 (SNOT-22) score from baseline at the initial consult appointment to the 12 month follow-up appointment. The minimum possible score is 0 and the maximum is 110. A higher score indicates more sino-nasal symptoms/worse outcome. | Baseline and 12 months after initial consult appointment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sino-Nasal Outcome Test, Smell Test