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

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

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:

1. to learn more about the effects of smell retraining therapy on smell loss following COVID-19 and
2. to determine if budesonide-saline irrigations make smell retraining therapy more effective.

Study Overview

• Status: Terminated
• Conditions: Covid19; Anosmia; Dysosmia
• Intervention / Treatment: Other: Smell Retraining; Drug: Budesonide

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Smell Retraining Only; 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; Smell practice with household scented items; Other Names: Smell Training; Olfactory Retraining
Experimental: Smell Retraining + Budesonide; 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; Smell practice with household scented items; Other Names: Smell Training; Olfactory Retraining; Drug: Budesonide; Nasal irrigation with liquid steroid; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Loss of Taste Question Score From Baseline to First Follow-up	Change in loss of taste 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 taste from 0 (no loss) to 10 (total loss). A higher score indicates less taste/worse outcome.	Before and after 8-12 weeks of smell retraining
Change in Anxiety Question Score From Baseline to First Follow-up	Change in anxiety 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 anxiety from 0 (no anxiety) to 10 (worst possible anxiety). A higher score indicates more anxiety/worse outcome.	Before and after 8-12 weeks of smell retraining

Collaborators and Investigators

• Sponsor: Amanda Stapleton
• Investigators: Principal Investigator: Amanda L Stapleton, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): March 29, 2023

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Sino-Nasal Outcome Test; Smell Test
• Additional Relevant MeSH Terms: Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurologic Manifestations; Sensation Disorders; Olfaction Disorders; COVID-19; Anosmia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide; Glucocorticoids
• Other Study ID Numbers: STUDY21050012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) may be shared, after de-identification, with researchers who provide a methodologically sound proposal. IPD to be shared will include that necessary to achieve the aims in the approved proposal.
• IPD Sharing Time Frame: Beginning 1 year after publication of summary data. Ending 5 years after publication.
• IPD Sharing Access Criteria: Proposals should be directed to shafferad@upmc.edu. To gain access, data requestors will need to sign data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No