Coronavirus Disease 2019Phase 2NCT04900415
Olfactory and Neurosensory Rehabilitation in COVID-19-related Olfactory Dysfunction
A Phase 2 study testing Vitamin A and Electronic portable aromatic rehabilitation (EPAR) diffuser in people with Coronavirus Disease 2019, run by Ivan FN Hung MD at 2 sites in Hong Kong.
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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Coronavirus Disease 2019
- What is being tested?
- Vitamin A and Electronic portable aromatic rehabilitation (EPAR) diffuser
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesHong Kong
- Study dates
- 22 Jul 2020to 30 Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Hong Kong2 sites, 2 recruiting
- Recruiting
Pamela Youde Nethersole Eastern Hospital
Hong Kong
Fergus Kai-Chuen Wong, FRCSEd(ORL), 25956111, wongkaichuen@gmail.com
- Recruiting
The University of Hong Kong, Queen Mary Hospital
Hong Kong
Ivan Fan Ngai Hung, MD, 22554049, ivanhung@hku.hk
About this study
Official title: 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).
Read the 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).
- Conditions
- Coronavirus Disease 2019
- Being tested
- Vitamin A, Electronic portable aromatic rehabilitation (EPAR) diffuser
- Keywords
- Vitamin A, Smell training, COVID-19, Olfactory dysfunction, Anosmia, Functional MRI
- Medical subject headings
- COVID-19, Anosmia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin ADrug
Metabolic supplement for neurogenesis at the olfactory apparatus
Electronic portable aromatic rehabilitation (EPAR) diffuserDevice
Handheld essential oil ultrasonication diffuser technology
| Study group | Role | What they receive |
|---|---|---|
| Vitamin A and smell training | Experimental | 14-day course of daily oral vitamin A 7500µg RAE in combination with smell training three times per day for 4 weeks Receives: Drug: Vitamin A; Device: Electronic portable aromatic rehabilitation (EPAR) diffuser |
| Smell training | Active comparator | Smell training three times per day for 4 weeks Receives: Device: Electronic portable aromatic rehabilitation (EPAR) diffuser |
| Control | No intervention | Observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective olfactory assessment
Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).
Measured: 4 weeks
Objective olfactory assessment by the butanol threshold test (BTT)
Objective measurements of olfactory sensitivity, as determined by the detection of different concentrations of butanol.
Measured: 4 weeks
Objective olfactory assessment by the smell identification test (SIT)
Objective categorization of olfactory status by the smell identification test (SIT).
Measured: 4 weeks
Secondary outcomes (5)
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)
Measured: 2 weeks
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2021
- Study start22 Jul 2020
- Primary completion12 Mar 2021
- Study completion30 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronavirus Disease 2019Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ivan FN Hung MD
- Sponsor type
- University, hospital or other
- Collaborators
- Pamela Youde Nethersole Eastern Hospital
- Responsible party
- Sponsor-investigator, Ivan FN Hung MD, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04900415
- Sponsor's protocol ID
- UW 20-454
- Status last verified
- May 2021
- First submitted
- 17 May 2021
- Last updated
- 25 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Olfactory and Neurosensory Rehabilitation in Coronavirus 2019 (COVID-19)-Related Olfactory Dysfunction (OD)
- ClinicalTrials.gov ID
- NCT04900415
- Acronym / sponsor ID
- UW 20-454
- Conditions
- Coronavirus Disease 2019
- Keywords
- Vitamin A, Smell training, COVID-19, Olfactory dysfunction, Anosmia, Functional MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Ivan FN Hung MDUniversity, hospital or other
- Collaborators
- Pamela Youde Nethersole Eastern Hospital
- Study start
- 22 Jul 2020 (actual)
- Primary completion
- 12 Mar 2021 (actual)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 25 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
- 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
| Arm | Type | Receives |
|---|---|---|
| Vitamin A and smell training | Experimental | Drug: Vitamin A, Device: Electronic portable aromatic rehabilitation (EPAR) diffuser14-day course of daily oral vitamin A 7500µg RAE in combination with smell training three times per day for 4 weeks |
| Smell training | Active comparator | Device: Electronic portable aromatic rehabilitation (EPAR) diffuserSmell training three times per day for 4 weeks |
| Control | No intervention | –Observation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- All subjects give written informed consent
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin AMetabolic supplement for neurogenesis at the olfactory apparatus | Drug | Vitamin A and smell training |
| Electronic portable aromatic rehabilitation (EPAR) diffuserHandheld essential oil ultrasonication diffuser technology | Device | Smell training, Vitamin A and smell training |
Primary outcome
Subjective olfactory assessment
Time frame: 4 weeks
Subjective olfactory assessment by the Sino-Nasal Outcome Test (SNOT-22).
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.
Objective olfactory assessment by the smell identification test (SIT)
Time frame: 4 weeks
Objective categorization of olfactory status by the smell identification test (SIT).
5 secondary outcomes
Interim neuroradiological changes after 2 weeks of olfactory treatment
Time frame: 2 weeks
Neuroradiological changes after olfactory treatment at the end of study
Time frame: 4 weeks
Interim neuroradiological changes after oral vitamin A in combination with smell training versus smell training alone
Time frame: 2 weeks
Neuroradiological brain changes in the intervention group versus observation group at the end of study
Time frame: 4 weeks
Neuroradiological brain changes in the intervention group versus healthy control group at the end of study
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Individual participant dataSharing planned: No
Related trials for Coronavirus Disease 2019
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin A and Electronic portable aromatic rehabilitation (EPAR) diffuser in people with Coronavirus Disease 2019, run by Ivan FN Hung MD at 2 sites in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ivan Fan Ngai Hung, MD (22554049, ivanhung@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjective olfactory assessment (time frame: 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.