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

Ivan FN Hung MD

Status and phase: Unknown; Phase 2

Conditions: Coronavirus Disease 2019

Treatments: Drug: Vitamin A; Device: Electronic portable aromatic rehabilitation (EPAR) diffuser

Study type: Interventional

Funder types: Other

Identifiers

NCT04900415

UW 20-454

Details and patient eligibility

About

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).

Full 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).

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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25 participants in 3 patient groups

Vitamin A and smell training

Experimental group

Description:

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

Treatment:

Device: Electronic portable aromatic rehabilitation (EPAR) diffuser

Drug: Vitamin A

Smell training

Active Comparator group

Description:

Smell training three times per day for 4 weeks

Treatment:

Device: Electronic portable aromatic rehabilitation (EPAR) diffuser

Control

No Intervention group

Description:

Observation