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

Active, not recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

40

Phase

  • 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 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

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
Intervention / Treatment
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

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

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)

March 15, 2025

Primary Completion (Estimated)

May 15, 2026

Study Completion (Estimated)

October 15, 2026

Study Registration Dates

First Submitted

January 28, 2025

First Submitted That Met QC Criteria

February 5, 2025

First Posted (Actual)

February 10, 2025

Study Record Updates

Last Update Posted (Estimated)

August 27, 2025

Last Update Submitted That Met QC Criteria

August 26, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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