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

May 21, 2021 updated by: Ivan FN Hung MD

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ivan Fan Ngai Hung, MD
  • Phone Number: 22554049
  • Email: ivanhung@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Pamela Youde Nethersole Eastern Hospital
        • Contact:
      • Hong Kong, Hong Kong
        • Recruiting
        • The University of Hong Kong, Queen Mary Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adult out-patient (≥18 years of age)
  2. 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)
  3. Complaints of persistent olfactory disturbances, subjectively

  4. Quantitatively documented to have olfactory dysfunction by

    1. Butanol threshold test (BTT)
    2. Smell identification test (SIT)
  5. All subjects give written informed consent
  6. Subjects must be available to complete the study and comply with study procedures.

Exclusion Criteria:

  1. Inability to comprehend and to follow all required study procedures
  2. Allergy or severe reactions to the study drug or smell training
  3. Pregnant or breastfeeding women
  4. 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…)
  5. 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.
  6. Have any condition that the investigator believes may interfere with successful completion of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vitamin A and smell training
14-day course of daily oral vitamin A 7500µg RAE in combination with smell training three times per day for 4 weeks
Drug: Vitamin A
Metabolic supplement for neurogenesis at the olfactory apparatus
Device: Electronic portable aromatic rehabilitation (EPAR) diffuser
Handheld essential oil ultrasonication diffuser technology
Active Comparator: Smell training
Smell training three times per day for 4 weeks
Device: Electronic portable aromatic rehabilitation (EPAR) diffuser
Handheld essential oil ultrasonication diffuser technology
No Intervention: Control
Observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective olfactory assessment
Time Frame: 4 weeks
Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).
4 weeks
Objective olfactory assessment by the butanol threshold test (BTT)
Time Frame: 4 weeks
Objective measurements of olfactory sensitivity, as determined by the detection of different concentrations of butanol.
4 weeks
Objective olfactory assessment by the smell identification test (SIT)
Time Frame: 4 weeks
Objective categorization of olfactory status by the smell identification test (SIT).
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Interim neuroradiological changes after 2 weeks of olfactory treatment
Time Frame: 2 weeks
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)
2 weeks
Neuroradiological changes after olfactory treatment at the end of study
Time Frame: 4 weeks
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.
4 weeks
Interim neuroradiological changes after oral vitamin A in combination with smell training versus smell training alone
Time Frame: 2 weeks
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.
2 weeks
Neuroradiological brain changes in the intervention group versus observation group at the end of study
Time Frame: 4 weeks
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.
4 weeks
Neuroradiological brain changes in the intervention group versus healthy control group at the end of study
Time Frame: 4 weeks
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.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ivan FN Hung MD

Collaborators

Pamela Youde Nethersole Eastern Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 22, 2020

Primary Completion (Actual)

March 12, 2021

Study Completion (Anticipated)

June 30, 2021

Study Registration Dates

First Submitted

May 17, 2021

First Submitted That Met QC Criteria

May 21, 2021

First Posted (Actual)

May 25, 2021

Study Record Updates

Last Update Posted (Actual)

May 25, 2021

Last Update Submitted That Met QC Criteria

May 21, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 20-454

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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