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

Coronavirus Disease 2019 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04900415
• Other study ID #: UW 20-454
• Status: Recruiting
• Phase: Phase 2
• Start date: July 22, 2020
• Est. completion date: June 30, 2021

Study information

• Verified date: May 2021
• Source: The University of Hong Kong
• Contact: Ivan Fan Ngai Hung, MD
• Phone: 22554049
• Email: ivanhung[@]hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: June 30, 2021
• Est. primary completion date: March 12, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Disease 2019
• Coronavirus Infections

Intervention

Drug:
• Vitamin A
Metabolic supplement for neurogenesis at the olfactory apparatus

Device:
• Electronic portable aromatic rehabilitation (EPAR) diffuser
Handheld essential oil ultrasonication diffuser technology

Locations

Country	Name	City	State
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Hong Kong
Hong Kong	The University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
Ivan FN Hung MD	Pamela Youde Nethersole Eastern Hospital

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjective olfactory assessment	Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).	4 weeks
Primary	Objective olfactory assessment by the butanol threshold test (BTT)	Objective measurements of olfactory sensitivity, as determined by the detection of different concentrations of butanol.	4 weeks
Primary	Objective olfactory assessment by the smell identification test (SIT)	Objective categorization of olfactory status by the smell identification test (SIT).	4 weeks
Secondary	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)	2 weeks
Secondary	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.	4 weeks
Secondary	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.	2 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks