Olfactory Training in COVID-19 Associated Loss of Smell

April 17, 2025 updated by: Medical University Innsbruck

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.

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:

  1. objective olfactory testing with the Sniffin' sticks test (identification and discrimination),
  2. subjective OD and its impact on the daily life,
  3. other clinical scales and questionnaires referring to OD-related mood and quality of life,
  4. 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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

70

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

  • Austria
    • Tirol
      • Innsbruck, Tirol, Austria, 6020
        • Medical University of Innsbruck

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: olfactory training group
12 weeks of olfactory traiing with Sniffin' sticks "Duftquartett".
Device: Sniffin' sticks Duftquartett
4-odor training set over 12 weeks with Sniffin' sticks "Duftquartett"
No Intervention: no olfactory training with natural history of the disease
natural history of the disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
primary endpoint
Time Frame: 12 weeks
changes between groups from baseline to week 12/termination visit regarding correct odor identification and discrimination
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mood inventory
Time Frame: 12 weeks
Will be applied in German
12 weeks
Patient Progress and treatment response over time
Time Frame: 12 weeks
Using Patient Global Impression of Improvement
12 weeks
Clinical treatment response over time
Time Frame: 12 weeks
Using Clinical Global Impression of Improvement
12 weeks
Visual Analog Scale
Time Frame: 12 weeks
from 0 to 10, higher score means better subjective olfaction
12 weeks
Short-Form-36 Health Survey Questionnaire (SF-36)
Time Frame: 12 weeks
Quality of Life Each domain is scored from 0 to 100, higher scores mean better health status
12 weeks
Hospital Anxiety and Depression Scale
Time Frame: 12 weeks
Anxiety and Depression Each item is scored on a 4-point scale from 0 to 3; lower scores mean less anxiety/depression
12 weeks

Collaborators and Investigators

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

Sponsor

Medical University Innsbruck

Investigators

  • Study Chair: Beatrice Heim, MD PhD, Medical University of Innsbruck

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)

August 10, 2022

Primary Completion (Actual)

December 31, 2024

Study Completion (Actual)

December 31, 2024

Study Registration Dates

First Submitted

June 15, 2022

First Submitted That Met QC Criteria

June 15, 2022

First Posted (Actual)

June 16, 2022

Study Record Updates

Last Update Posted (Actual)

April 23, 2025

Last Update Submitted That Met QC Criteria

April 17, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12732020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data supporting the results will be archived in an appropriate public repository

IPD Sharing Time Frame

after publication of the primary data

IPD Sharing Access Criteria

data will be deposited in appropriate public repositories

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Subscribe