Treatment of Olfactory Dysfunction Using Vagus Nerve Stimulation

NCT06817499 | Active Not Recruiting

• 2 other identifiers: 2023-03779-01_s32021-06527
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hyposmia

Keywords

VNS; Hyposmia; Olfaction; Olfaction Disorders; Sensation Disorders; Vagus Nerve

Outcome Measures

Primary Outcomes (4)

• 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.

  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"

  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).

  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?"

  From enrollment to the end of treatment at 8 weeks

Study Arms (2)

Olfactory training with nasal inserts + VNS

EXPERIMENTAL

Participants will complete olfactory training with scented nose plugs along with VNS

Other: Nasal Insert + VNS

Olfactory training with nasal inserts only

ACTIVE COMPARATOR

Participants will complete olfactory training with scented nose plugs

Other: Nasal Insert

Interventions

Nasal Insert + VNS OTHER

Participants will complete olfactory training with scented nose plugs along with VNS

Olfactory training with nasal inserts + VNS

Nasal Insert OTHER

Participants will complete olfactory training with scented nose plugs

Olfactory training with nasal inserts only

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Karolinska Institutet

Solna, Stockholm County, 17165, Sweden

Location

MeSH Terms

Conditions

Anosmia; Olfaction Disorders; Sensation Disorders

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 10, 2025
• Study Start: March 15, 2025
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

SE (1)