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Olfactory and Neurosensory Rehabilitation in COVID-19-related Olfactory Dysfunction

Primary Purpose

Coronavirus Disease 2019

Status

Unknown status

Phase

Phase 2

Locations

Hong Kong

Study Type

Interventional

Intervention

Vitamin A

Electronic portable aromatic rehabilitation (EPAR) diffuser

About this trial

This is an interventional treatment trial for Coronavirus Disease 2019 focused on measuring Vitamin A, Smell training, COVID-19, Olfactory dysfunction, Anosmia, Functional MRI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Adult out-patient (≥18 years of age)
Previously diagnosed with coronavirus disease 2019 (COVID-19) by laboratory confirmation using reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of severe acute respiratory virus coronavirus 2 (SARS-CoV-2)
Complaints of persistent olfactory disturbances, subjectively
Quantitatively documented to have olfactory dysfunction by
1. Butanol threshold test (BTT)
2. Smell identification test (SIT)
All subjects give written informed consent
Subjects must be available to complete the study and comply with study procedures.

Exclusion Criteria:

Inability to comprehend and to follow all required study procedures
Allergy or severe reactions to the study drug or smell training
Pregnant or breastfeeding women
Pre-existing factors which may account for persistent olfactory dysfunction besides COVID-19 (e.g. nasal polyps, obstructive lesions within the nasal cavity, severe anatomical malformations…)
Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study.
Have any condition that the investigator believes may interfere with successful completion of the study.

Sites / Locations

Pamela Youde Nethersole Eastern HospitalRecruiting
The University of Hong Kong, Queen Mary HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Vitamin A and smell training

Smell training

Control

Arm Description

14-day course of daily oral vitamin A 7500µg RAE in combination with smell training three times per day for 4 weeks

Smell training three times per day for 4 weeks

Observation

Outcomes

Primary Outcome Measures

Subjective olfactory assessment

Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).

Objective olfactory assessment by the butanol threshold test (BTT)

Objective measurements of olfactory sensitivity, as determined by the detection of different concentrations of butanol.

Objective olfactory assessment by the smell identification test (SIT)

Objective categorization of olfactory status by the smell identification test (SIT).

Secondary Outcome Measures

Interim neuroradiological changes after 2 weeks of olfactory treatment

Group independent component (GIC) and cerebral network functional connectivity (FC) analyses of the olfactory, gustatory, somatosensory, and integrative networks using rs-fMRI scans, before and at 2 weeks after olfactory treatment in COVID-19 patients with olfactory dysfunction (OD)

Neuroradiological changes after olfactory treatment at the end of study

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, before and after treatment in COVID-19 patients with olfactory dysfunction at 4 weeks.

Interim neuroradiological changes after oral vitamin A in combination with smell training versus smell training alone

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, between combined VitA and smell training (ST) versus ST alone in COVID-19 patients with olfactory dysfunction at 2 weeks.

Neuroradiological brain changes in the intervention group versus observation group at the end of study

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, in the interventional versus control arms (observation) in COVID-19 patients with olfactory dysfunction at 4 weeks.

Neuroradiological brain changes in the intervention group versus healthy control group at the end of study

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, in COVID-19 patients with olfactory dysfunction compared with healthy controls at 4 weeks.

Full Information

NCT ID

NCT04900415

First Posted

May 17, 2021

Last Updated

May 21, 2021

Sponsor

Ivan FN Hung MD

Collaborators

Pamela Youde Nethersole Eastern Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04900415

Brief Title

Olfactory and Neurosensory Rehabilitation in COVID-19-related Olfactory Dysfunction

Official Title

Olfactory and Neurosensory Rehabilitation in Coronavirus 2019 (COVID-19)-Related Olfactory Dysfunction (OD)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Unknown status

Study Start Date

July 22, 2020 (Actual)

Primary Completion Date

March 12, 2021 (Actual)

Study Completion Date

June 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Ivan FN Hung MD

Collaborators

Pamela Youde Nethersole Eastern Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

A combination of oral vitamin A (VitA) and intense aromatic chemosensory smell training (ST) by pulse aromatic stimulation will expedite the neurosensory recovery of olfaction in patients suffering from prolonged COVID-19-related olfactory dysfunction (OD).

Detailed Description

This is an open-labeled randomised-controlled trial (RCT) investigating the safety and therapeutic efficacy of oral VitA in combination with ST for patients suffering from prolonged COVID-19-related OD. Prior to the initiation of treatment, all patients will receive subjective and objective olfactory assessments. Comprehensive ear, nose, and throat (ENT) examination will be performed to rule out alternative causes of OD. All participants will receive resting-state functional magnetic resonance imaging (rs-fMRI) of the brain before treatment as baseline evaluation. Patients with prolonged COVID-19-related OD will be assigned to the intervention (group A or B) or control (group C) arms: Intervention arm A. 14-day course of daily oral VitA 7500µg RAE (retinol activity equivalents) in combination with ST three times per day for 4 weeks; or B. ST three times per day for 4 weeks alone; or Control arm C. Observation In addition, healthy controls who were tested negative for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) will receive rs-fMRI brain scans for radiological comparisons. At the completion of the trial, subjective and objective olfactory assessments will be repeated to document clinical changes in olfaction. Follow-up rs-fMRI will be performed to document neuroradiological changes in the brain structures and cerebral network functional connectivity (FC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronavirus Disease 2019

Keywords

Vitamin A, Smell training, COVID-19, Olfactory dysfunction, Anosmia, Functional MRI

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Patients with prolonged COVID-19-related olfactory dysfunction will be assigned to the intervention (group A or B) or control (group C) arms: Intervention arm A. 14-day course of daily oral vitamin A 7500µg RAE (retinol activity equivalents) in combination with smell training three times per day for 4 weeks; or B. Smell training three times per day for 4 weeks alone; or Control arm C. Observation

Masking

InvestigatorOutcomes Assessor

Masking Description

All study participants will receive baseline and follow up resting-state functional (rs-fMRI) brain scans during the study period. The radiologists assessing and analysing the rs-fMRI images will be blinded to the treatment regimens received by the study subjects.

Allocation

Randomized

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Vitamin A and smell training

Arm Type

Experimental

Arm Description

14-day course of daily oral vitamin A 7500µg RAE in combination with smell training three times per day for 4 weeks

Arm Title

Smell training

Arm Type

Active Comparator

Arm Description

Smell training three times per day for 4 weeks

Arm Title

Control

Arm Type

No Intervention

Arm Description

Observation

Intervention Type

Drug

Intervention Name(s)

Vitamin A

Intervention Description

Metabolic supplement for neurogenesis at the olfactory apparatus

Intervention Type

Device

Intervention Name(s)

Electronic portable aromatic rehabilitation (EPAR) diffuser

Intervention Description

Handheld essential oil ultrasonication diffuser technology

Primary Outcome Measure Information:

Title

Subjective olfactory assessment

Description

Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).

Time Frame

4 weeks

Title

Objective olfactory assessment by the butanol threshold test (BTT)

Description

Objective measurements of olfactory sensitivity, as determined by the detection of different concentrations of butanol.

Time Frame

4 weeks

Title

Objective olfactory assessment by the smell identification test (SIT)

Description

Objective categorization of olfactory status by the smell identification test (SIT).

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Interim neuroradiological changes after 2 weeks of olfactory treatment

Description

Time Frame

2 weeks

Title

Neuroradiological changes after olfactory treatment at the end of study

Description

Time Frame

4 weeks

Title

Interim neuroradiological changes after oral vitamin A in combination with smell training versus smell training alone

Description

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, between combined VitA and smell training (ST) versus ST alone in COVID-19 patients with olfactory dysfunction at 2 weeks.

Time Frame

2 weeks

Title

Neuroradiological brain changes in the intervention group versus observation group at the end of study

Description

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, in the interventional versus control arms (observation) in COVID-19 patients with olfactory dysfunction at 4 weeks.

Time Frame

4 weeks

Title

Neuroradiological brain changes in the intervention group versus healthy control group at the end of study

Description

Group independent component analyses and functional connectivity analyses of the olfactory, gustatory, somatosensory, and integrative networks by resting-state functional MRI brain scans, in COVID-19 patients with olfactory dysfunction compared with healthy controls at 4 weeks.

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult out-patient (≥18 years of age) Previously diagnosed with coronavirus disease 2019 (COVID-19) by laboratory confirmation using reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of severe acute respiratory virus coronavirus 2 (SARS-CoV-2) Complaints of persistent olfactory disturbances, subjectively Quantitatively documented to have olfactory dysfunction by Butanol threshold test (BTT) Smell identification test (SIT) All subjects give written informed consent Subjects must be available to complete the study and comply with study procedures. Exclusion Criteria: Inability to comprehend and to follow all required study procedures Allergy or severe reactions to the study drug or smell training Pregnant or breastfeeding women Pre-existing factors which may account for persistent olfactory dysfunction besides COVID-19 (e.g. nasal polyps, obstructive lesions within the nasal cavity, severe anatomical malformations…) Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to recruitment in this study or expect to receive an experimental agent during this study. Unwilling to refuse participation in another clinical study through the end of this study. Have any condition that the investigator believes may interfere with successful completion of the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ivan Fan Ngai Hung, MD

Phone

22554049

ivanhung@hku.hk

Facility Information:

Facility Name

Pamela Youde Nethersole Eastern Hospital

City

Hong Kong

Country

Hong Kong

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fergus Kai-Chuen Wong, FRCSEd(ORL)

Phone

25956111

wongkaichuen@gmail.com

Facility Name

The University of Hong Kong, Queen Mary Hospital

City

Hong Kong

Country

Hong Kong

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ivan Fan Ngai Hung, MD

Phone

22554049

ivanhung@hku.hk

12. IPD Sharing Statement

Plan to Share IPD

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Olfactory and Neurosensory Rehabilitation in COVID-19-related Olfactory Dysfunction

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