Treatment of Olfactory Dysfunction Using Vagus Nerve Stimulation

August 26, 2025 updated by: Johan Lundström, Karolinska Institutet
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Sweden
    • Stockholm County
      • Solna, Stockholm County, Sweden, 17165
        • Karolinska Institutet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Correct age (18-65)
  • Physically and cognitively capable of participating in the study
  • Having appropriate olfactory screening test scores (hyposmic)

Exclusion Criteria:

  • History of heart conditions
  • Individuals with other diagnoses that could affect the study results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Olfactory training with nasal inserts + VNS
Participants will complete olfactory training with scented nose plugs along with VNS
Other: Nasal Insert + VNS
Participants will complete olfactory training with scented nose plugs along with VNS
Active Comparator: Olfactory training with nasal inserts only
Participants will complete olfactory training with scented nose plugs
Other: Nasal Insert
Participants will complete olfactory training with scented nose plugs

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
From enrollment to the end of treatment at 8 weeks
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"
From enrollment to the end of treatment at 8 weeks
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).
From enrollment to the end of treatment at 8 weeks
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?"
From enrollment to the end of treatment at 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Karolinska Institutet

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 15, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 15, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2025

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 27, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2023-03779-01_s3
  • 2021-06527 (Other Grant/Funding Number: Swedish Research Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

anonymized data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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