HyposmiaNCT06817499
Treatment of Olfactory Dysfunction Using Vagus Nerve Stimulation
A study testing Nasal Insert + VNS and Nasal Insert in people with Hyposmia, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
Hyposmia, a reduced sense of smell, is commonly linked to viral infections like COVID-19. Currently, the sole recommended treatment is olfactory training, a method that is both time-intensive and limited in its effectiveness. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hyposmia
- What is being tested?
- Nasal Insert + VNS and Nasal Insert
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSweden
- Study dates
- 15 Mar 2025to 15 Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Correct age (18-65)
- Physically and cognitively capable of participating in the study
- Having appropriate olfactory screening test scores (hyposmic)
Who cannot join
- History of heart conditions
- Individuals with other diagnoses that could affect the study results
Trial locations and contacts
1 site in 1 country.
About this study
Hyposmia, a reduced sense of smell, is commonly linked to viral infections like COVID-19. Currently, the sole recommended treatment is olfactory training, a method that is both time-intensive and limited in its effectiveness. Our team has previously evaluated a new type of olfactory training using nasal inserts that show increased adherence to training (compared to standard olfactory training using common household odors) but with similar treatment effect. The investigators recently demonstrated that brief transcutaneous vagus nerve stimulation (VNS) in the cymba conchae region affected participants olfactory abilities but only when a stimulation frequency relevant to olfactory bulb processing frequencies was used. The notion that VNS might modulate olfactory functions stems from findings in rats where VNS of the cervical nerve inhibited neurons within the periglomerular layers of the olfactory bulb. Although there is no known monosynaptic connection between the vagus nerve and the olfactory system in humans, VNS activates areas with mono-synaptic connections to the olfactory bulb, such as amygdala, hippocampus, and the hypothalamus. Given that VNS modulates the olfactory bulb in rats and our treatment protocol modulate olfactory functions in humans, the investigators hypothesize that VNS, when paired with olfactory training, will enhance olfactory functions in patients with hyposmia.
Read the detailed description
Participants with hyposmia will be recruited and randomly assigned to one of two treatment groups. One group will engage in olfactory training using nasal inserts while the other will use olfactory training with nasal inserts along with VNS. Both interventions will take place at home, Monday through Friday, over a two-month period. To evaluate the outcomes, subjective and objective measures of olfactory function will be collected before, during, and after the treatment, along with assessments of quality of life and overall well-being. Treatment adherence will also be evaluated at the end of treatment.
- Conditions
- Hyposmia
- Being tested
- Nasal Insert + VNS, Nasal Insert
- Keywords
- VNS, Hyposmia, Olfaction, Olfaction Disorders, Sensation Disorders, Vagus Nerve
- Medical subject headings
- Anosmia, Olfaction Disorders, Sensation Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nasal Insert + VNSOther
Participants will complete olfactory training with scented nose plugs along with VNS
Nasal InsertOther
Participants will complete olfactory training with scented nose plugs
| Study group | Role | What they receive |
|---|---|---|
| Olfactory training with nasal inserts + VNS | Experimental | Participants will complete olfactory training with scented nose plugs along with VNS Receives: Other: Nasal Insert + VNS |
| Olfactory training with nasal inserts only | Active comparator | Participants will complete olfactory training with scented nose plugs Receives: Other: Nasal Insert |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sniffin' Sticks TDI test (objective olfactory function)
Objective olfactory function will be measured using the Sniffin' Sticks TDI extended test (Burghart Messtechnik) which gives separate scores for odor threshold, odor discrimination, and odor identification; as well as a summated score (TDI) of objective olfactory function.
Measured: From enrollment to the end of treatment at 8 weeks
Self rated olfaction questionnaire (subjective olfactory function)
Does the use of VNS increase the effect of olfactory training on subjective qualitative (parosmia) and quantitative (hyposmia) symptoms compared to only olfactory training? For this outcome, we will use self-ratings of qualitative and quantitative olfactory function, for example "Do you experience smell distortion (parosmia)?" (if yes, rate your problem from 0 to 10) and "rate your sense of smell from 0 to 10"
Measured: From enrollment to the end of treatment at 8 weeks
General Wellbeing Questionnaire (general wellbeing)
Does the use of VNS increase the effect of olfactory training on subjective general wellbeing compared to only olfactory training? For this outcome, we will use the General Wellbeing Questionnaire (GWB).
Measured: From enrollment to the end of treatment at 8 weeks
Adherence to training questionnaire (Compliance)
Does the use of VNS affect the compliance of olfactory training compared to olfactory training only? For this outcome, we will use a questionnaire that participants answer during their final visit. The questionnaire separately assesses consistency, perceived tediousness, forgetfulness, and cause for potential discontinuation of the training, for example by asking "how many times did you forget your training?"
Measured: From enrollment to the end of treatment at 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start15 Mar 2025
- Primary completion15 May 2026 (estimated)
- Study completion15 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyposmiaStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe 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
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Johan Lundström, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06817499
- Sponsor's protocol ID
- 2023-03779-01_s3
- Other IDs
- 2021-06527, 2023
- Status last verified
- Aug 2025
- First submitted
- 28 Jan 2025
- Last updated
- 27 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: anonymized data
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Olfactory Dysfunction Using Vagus Nerve Stimulation
- ClinicalTrials.gov ID
- NCT06817499
- Acronym / sponsor ID
- 2023-03779-01_s3
- Conditions
- Hyposmia
- Keywords
- VNS, Hyposmia, Olfaction, Olfaction Disorders, Sensation Disorders, Vagus Nerve
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Study start
- 15 Mar 2025 (actual)
- Primary completion
- 15 May 2026 (estimated)
- Study completion
- 15 Oct 2026 (estimated)
- First posted
- 10 Feb 2025 (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.
Hyposmia, a reduced sense of smell, is commonly linked to viral infections like COVID-19. Currently, the sole recommended treatment is olfactory training, a method that is both time-intensive and limited in its effectiveness. Our team has previously evaluated a new type of olfactory training using nasal inserts that show increased adherence to training (compared to standard olfactory training using common household odors) but with similar treatment effect. The investigators recently demonstrated that brief transcutaneous vagus nerve stimulation (VNS) in the cymba conchae region affected participants olfactory abilities but only when a stimulation frequency relevant to olfactory bulb processing frequencies was used. The notion that VNS might modulate olfactory functions stems from findings in rats where VNS of the cervical nerve inhibited neurons within the periglomerular layers of the olfactory bulb. Although there is no known monosynaptic connection between the vagus nerve and the olfactory system in humans, VNS activates areas with mono-synaptic connections to the olfactory bulb, such as amygdala, hippocampus, and the hypothalamus. Given that VNS modulates the olfactory bulb in rats and our treatment protocol modulate olfactory functions in humans, the investigators hypothesize that VNS, when paired with olfactory training, will enhance olfactory functions in patients with hyposmia.
Detailed description
Participants with hyposmia will be recruited and randomly assigned to one of two treatment groups. One group will engage in olfactory training using nasal inserts while the other will use olfactory training with nasal inserts along with VNS. Both interventions will take place at home, Monday through Friday, over a two-month period. To evaluate the outcomes, subjective and objective measures of olfactory function will be collected before, during, and after the treatment, along with assessments of quality of life and overall well-being. Treatment adherence will also be evaluated at the end of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olfactory training with nasal inserts + VNS | Experimental | Other: Nasal Insert + VNSParticipants will complete olfactory training with scented nose plugs along with VNS |
| Olfactory training with nasal inserts only | Active comparator | Other: Nasal InsertParticipants will complete olfactory training with scented nose plugs |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Correct age (18-65)
- Physically and cognitively capable of participating in the study
- Having appropriate olfactory screening test scores (hyposmic)
Key exclusion criteria (2 listed)
- History of heart conditions
- Individuals with other diagnoses that could affect the study results
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 |
|---|---|---|
| Nasal Insert + VNSParticipants will complete olfactory training with scented nose plugs along with VNS | Other | Olfactory training with nasal inserts + VNS |
| Nasal InsertParticipants will complete olfactory training with scented nose plugs | Other | Olfactory training with nasal inserts only |
Primary outcome
Sniffin' Sticks TDI test (objective olfactory function)
Time frame: From enrollment to the end of treatment at 8 weeks
Objective olfactory function will be measured using the Sniffin' Sticks TDI extended test (Burghart Messtechnik) which gives separate scores for odor threshold, odor discrimination, and odor identification; as well as a summated score (TDI) of objective olfactory function.
Self rated olfaction questionnaire (subjective olfactory function)
Time frame: From enrollment to the end of treatment at 8 weeks
Does the use of VNS increase the effect of olfactory training on subjective qualitative (parosmia) and quantitative (hyposmia) symptoms compared to only olfactory training? For this outcome, we will use self-ratings of qualitative and quantitative olfactory function, for example "Do you experience smell distortion (parosmia)?" (if yes, rate your problem from 0 to 10) and "rate your sense of smell from 0 to 10"
General Wellbeing Questionnaire (general wellbeing)
Time frame: From enrollment to the end of treatment at 8 weeks
Does the use of VNS increase the effect of olfactory training on subjective general wellbeing compared to only olfactory training? For this outcome, we will use the General Wellbeing Questionnaire (GWB).
Adherence to training questionnaire (Compliance)
Time frame: From enrollment to the end of treatment at 8 weeks
Does the use of VNS affect the compliance of olfactory training compared to olfactory training only? For this outcome, we will use a questionnaire that participants answer during their final visit. The questionnaire separately assesses consistency, perceived tediousness, forgetfulness, and cause for potential discontinuation of the training, for example by asking "how many times did you forget your training?"
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
- Individual participant dataSharing planned: Yes. anonymized data
Related trials for Hyposmia
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
Topical Versus Injection PRP for Olfactory Dysfunction
Olfactory Dysfunction, Anosmia
Not yet recruiting
SniffTrain: Effectiveness of Sniff Training in the Treatment of Post-Viral Anosmia
Post-viral Anosmia, Anosmia
Not yet recruitingObservational study
Artificial Intelligence-based Parkinson's Disease Risk Assessment (AI-PRA) Study
Parkinson Disease (PD), REM Sleep Behavior Disorder (iRBD)
Recruiting
Olfactory Training as a Treatment for Olfactory Dysfunction Post COVID-19
Hyposmia, 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nasal Insert + VNS and Nasal Insert in people with Hyposmia, run by Karolinska Institutet at 1 site in Sweden.
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 3 inclusion and 2 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: under way, not looking for participants, as of the sponsor's last update on 27 Aug 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 Sweden. 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?
This study is still under way. Results are not available in the source record yet.
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?
Sniffin' Sticks TDI test (objective olfactory function) (time frame: From enrollment to the end of treatment at 8 weeks). The study lists 4 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 27 Aug 2025.