COVID-19NCT05421221
Olfactory Training in COVID-19 Associated Loss of Smell
A study testing Sniffin' sticks Duftquartett in people with COVID-19 and Hyposmia, run by Medical University Innsbruck at 1 site in Austria.
Trial summary
Olfactory dysfunction (OD) like hyposmia or anosmia has been realized as a common symptom or even cardinal sign of the disease and can be persisting after recovering. There are two different hypotheses on the pathogenesis of OD in past COVID-19: The central hypothesis, which speculates on neurotrophic abilities on… Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Sniffin' sticks Duftquartett
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteAustria
- Study dates
- 10 Aug 2022to 31 Dec 2024
- Phase
- Interventional
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject is aged over 18 years;
- confirmed diagnosis of COVID-19 at least three months ago (history of positive PCR-testing required) or positive serum nucleocapsid antibody titer against SARS-CoV2;
- post-infectious COVID-19 related olfactory dysfunction persisting for at least three months with abnormal Sniffin' sticks test (<13/16 items correct in the identification part);
- the patient is willing to undergo odor training over 12 weeks;
- written ICF is obtained.
Who cannot join
- History of olfactory dysfunction prior to COVID-19 infection due to other conditions e.g. status post traumatic brain injury, Parkinson's disease, allergic rhinitis, etc.;
- Nasal pathology not related to COVID-19 in the systematic otorhinolaryngological examination including endoscopy.
- the participant is pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial of the Effectiveness of Olfactory Training on Loss of Smell Related to COVID-19 (SMELL)
Olfactory dysfunction (OD) like hyposmia or anosmia has been realized as a common symptom or even cardinal sign of the disease and can be persisting after recovering.
There are two different hypotheses on the pathogenesis of OD in past COVID-19: The central hypothesis, which speculates on neurotrophic abilities on olfactory receptors in the neuroepithelium, and the peripheral hypothesis, which speculates on damage of the sensory olfactory epithelium.
Read more
Potential treatment strategies aim for the unique neural plasticity of the olfactory system and its potential for recovery.
Clinical studies and case reports have shown a promising effect of olfactory training (OT) by frequent sniffing and/or exposure to odors 2-4 times a day for several weeks.
The main objective of the study is to assess the effects of olfactory training in patients with COVID-19 related OD on:
- objective olfactory testing with the Sniffin' sticks test (identification and discrimination),
- subjective OD and its impact on the daily life,
- other clinical scales and questionnaires referring to OD-related mood and quality of life,
- gender differences in COVID-19 related OD. Approach / methods OT will be performed twice a day with a 4-odor training set for 12 weeks. Effects of OT on COVID-19 related OD will be measured with objective and subjective efficacy variables.
The sense of smell is an important function for social relationships and is therefore a challenging clinical problem with few proven therapeutic options.
With this new approach, we want to investigate a possible simple treatment for an impedimental symptom of COVID-19, but also learn more about the pathomechanism of post-infectious OD.
To our knowledge, this will be the first study comparing patients with COVID-19 associated OD with and without OT in clinical outcomes.
- Being tested
- Sniffin' sticks Duftquartett
- 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.
Sniffin' sticks DuftquartettDevice
4-odor training set over 12 weeks with Sniffin' sticks "Duftquartett"
| Study group | Role | What they receive |
|---|---|---|
| olfactory training group | Experimental | 12 weeks of olfactory traiing with Sniffin' sticks "Duftquartett". Receives: Device: Sniffin' sticks Duftquartett |
| no olfactory training with natural history of the disease | No intervention | natural history of the disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
primary endpoint
changes between groups from baseline to week 12/termination visit regarding correct odor identification and discrimination
Measured: 12 weeks
Secondary outcomes (6)
Visual Analog Scale
from 0 to 10, higher score means better subjective olfaction
Measured: 12 weeks
Short-Form-36 Health Survey Questionnaire (SF-36)
Quality of Life Each domain is scored from 0 to 100, higher scores mean better health status
Measured: 12 weeks
Mood inventory
Will be applied in German
Measured: 12 weeks
Hospital Anxiety and Depression Scale
Anxiety and Depression Each item is scored on a 4-point scale from 0 to 3; lower scores mean less anxiety/depression
Measured: 12 weeks
Patient Progress and treatment response over time
Using Patient Global Impression of Improvement
Measured: 12 weeks
Clinical treatment response over time
Using Clinical Global Impression of Improvement
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2022
- Study start10 Aug 2022
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Medical University InnsbruckThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University Innsbruck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Beatrice Heim, MD PhD, Study chair, Medical University Innsbruck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05421221
- Sponsor's protocol ID
- 12732020
- Status last verified
- Apr 2025
- First submitted
- 15 Jun 2022
- Last updated
- 23 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data supporting the results will be archived in an appropriate public repository
Publications
De Cleene N, Jagusch F, Schmutzhard J, Gottfried T, Peball M, Djamshidian A, Ellmerer P, Goebel G, Helbok R, Kindl P, Loffler-Ragg J, Weiss G, Seppi K, Heim B; SMELL study-group. Protocol for olfactory training in persisting COVID-19-associated loss of smell (SMELL): a monocentric randomised controlled trial conducted in Innsbruck. BMJ Open. 2025 May 27;15(5):e094027. doi: 10.1136/bmjopen-2024-094027.
PubMed 40436445
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of the Effectiveness of Olfactory Training on Loss of Smell Related to COVID-19 (SMELL)
- ClinicalTrials.gov ID
- NCT05421221
- Acronym / sponsor ID
- 12732020
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Medical University InnsbruckUniversity, hospital or other
- Study start
- 10 Aug 2022 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 16 Jun 2022 (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.
Olfactory dysfunction (OD) like hyposmia or anosmia has been realized as a common symptom or even cardinal sign of the disease and can be persisting after recovering.
There are two different hypotheses on the pathogenesis of OD in past COVID-19: The central hypothesis, which speculates on neurotrophic abilities on olfactory receptors in the neuroepithelium, and the peripheral hypothesis, which speculates on damage of the sensory olfactory epithelium.
Potential treatment strategies aim for the unique neural plasticity of the olfactory system and its potential for recovery.
Clinical studies and case reports have shown a promising effect of olfactory training (OT) by frequent sniffing and/or exposure to odors 2-4 times a day for several weeks.
The main objective of the study is to assess the effects of olfactory training in patients with COVID-19 related OD on:
- objective olfactory testing with the Sniffin' sticks test (identification and discrimination),
- subjective OD and its impact on the daily life,
- other clinical scales and questionnaires referring to OD-related mood and quality of life,
- gender differences in COVID-19 related OD. Approach / methods OT will be performed twice a day with a 4-odor training set for 12 weeks. Effects of OT on COVID-19 related OD will be measured with objective and subjective efficacy variables.
The sense of smell is an important function for social relationships and is therefore a challenging clinical problem with few proven therapeutic options.
With this new approach, we want to investigate a possible simple treatment for an impedimental symptom of COVID-19, but also learn more about the pathomechanism of post-infectious OD.
To our knowledge, this will be the first study comparing patients with COVID-19 associated OD with and without OT in clinical outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| olfactory training group | Experimental | Device: Sniffin' sticks Duftquartett12 weeks of olfactory traiing with Sniffin' sticks "Duftquartett". |
| no olfactory training with natural history of the disease | No intervention | –natural history of the disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- The subject is aged over 18 years;
- confirmed diagnosis of COVID-19 at least three months ago (history of positive PCR-testing required) or positive serum nucleocapsid antibody titer against SARS-CoV2;
- post-infectious COVID-19 related olfactory dysfunction persisting for at least three months with abnormal Sniffin' sticks test (<13/16 items correct in the identification part);
- the patient is willing to undergo odor training over 12 weeks;
- written ICF is obtained.
Key exclusion criteria (3 listed)
- History of olfactory dysfunction prior to COVID-19 infection due to other conditions e.g. status post traumatic brain injury, Parkinson's disease, allergic rhinitis, etc.;
- Nasal pathology not related to COVID-19 in the systematic otorhinolaryngological examination including endoscopy.
- the participant is pregnant
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 |
|---|---|---|
| Sniffin' sticks Duftquartett4-odor training set over 12 weeks with Sniffin' sticks "Duftquartett" | Device | olfactory training group |
Primary outcome
primary endpoint
Time frame: 12 weeks
changes between groups from baseline to week 12/termination visit regarding correct odor identification and discrimination
6 secondary outcomes
Visual Analog Scale
Time frame: 12 weeks
Short-Form-36 Health Survey Questionnaire (SF-36)
Time frame: 12 weeks
Mood inventory
Time frame: 12 weeks
Hospital Anxiety and Depression Scale
Time frame: 12 weeks
Patient Progress and treatment response over time
Time frame: 12 weeks
Clinical treatment response over time
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
- Derived from this study: PubMed 40436445De Cleene N, Jagusch F, Schmutzhard J, Gottfried T, Peball M, Djamshidian A, Ellmerer P, Goebel G, Helbok R, Kindl P, Loffler-Ragg J, Weiss G, Seppi K, Heim B; SMELL study-group. Protocol for olfactory training in persisting COVID-19-associated loss of smell (SMELL): a monocentric randomised controlled trial conducted in Innsbruck. BMJ Open. 2025 May 27;15(5):e094027. doi: 10.1136/bmjopen-2024-094027.
- Individual participant dataSharing planned: Yes. Data supporting the results will be archived in an appropriate public repository
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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.
Beatrice Heim, MD PhD study chair
Medical University Innsbruck
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sniffin' sticks Duftquartett in people with COVID-19 and Hyposmia, run by Medical University Innsbruck at 1 site in Austria.
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 5 inclusion and 3 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: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
primary endpoint (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05421221, which also lists 1 linked publication.
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 23 Apr 2025.