Recruiting
Phase 2
Phase 3

Smell Training & TNS

Sponsor:

Medical University of South Carolina

Code:

NCT05855369

Conditions

Smell Dysfunction

Olfactory Disorder

Long COVID

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Trigeminal Nerve Stimulation (TNS)

Active Smell Training (ST)

Placebo Smell Training (PBO)

Study Details

Brief summary:

Persistent smell loss that can include diminished or distorted smell function is a common symptom of long COVID syndrome. There are limited treatment options for long COVID-related smell loss. This study aims to determine the efficacy of two at-home treatments, smell training and non-invasive trigeminal nerve stimulation. This study requires participants to conduct daily at-home treatment sessions, attend three in-person study visits at the MUSC Department of Psychiatry and Behavioral Sciences, and complete electronic questionnaires over the 12-week trial, and again at the six-month timepoint. Participants in this trial may benefit directly with an improvement in sense of smell. However, participation may also help society more generally, as this study will provide new information about long COVID-related smell loss and its treatment.

Conditions

Smell Dysfunction

Olfactory Disorder

Long COVID

Study ID

NCT05855369

Start date

Oct 2, 2023

Status verified date

Apr, 2026

Completion date

May 31, 2028

Anticipated

Primary completion date

May 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • treatment-seeking for COVID-related persistent SL (anosmia, hyposmia, phantosmia or parosmia)
  • at least 1-month from SARS-coV-2 PCR-positive and/or rapid home-positive tests
  • normal sense of smell prior to COVID
  • naïve to both smell training (ST) and trigeminal nerve stimulation (TNS)
  • able to comprehend English and provide informed consent

Exclusion Criteria:

  • history of head injury (e.g. sport, accident, combat blast)
  • sinonasal condition (e.g. upper respiratory infection, rhinosinusitis, polyps)
  • neurological disorder (e.g. epilepsy, neurodegenerative disorder, narcolepsy)
  • serious mental illness (e.g. schizophrenia, bipolar, or other psychotic disorder)
  • suicidal ideation within the last month
  • current (≤6 months) heavy cigarette smoker (heavy defined as ≥ 10 pack-years)
  • oral/nasal steroids or other intranasal medications within the last month
  • immunomodulatory medications
  • pregnant or trying to become pregnant

Study Design

Enrollment

145 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Combination Trigeminal Nerve Stimulation (TNS) and active Smell Training (ST)

30 minutes of once/day TNS and twice/day ST conducted 5 days/week for 12 weeks and a total of 60 stimulation and 120 smell training sessions

active comparator: Active Smell Training (ST)

5 minutes of daily ST conducted twice/day, 5 days/week for 12 weeks and a total of 120 training session

placebo comparator: Placebo Smell Training (PBO)

5 minutes of daily PBO conducted twice/day, 5 days/week for 12 weeks and a total of 120 training sessions

Interventions

Trigeminal Nerve Stimulation (TNS)

Non-invasive, pain-free, low-level electrical stimulation to the forehead to modulate the trigeminal nerve and enhance smell function through activation of the highly connected olfactory-intranasal trigeminal brain circuits.

Active Smell Training (ST)

Sniffing various higher intensity odorant chemicals while performing odor-related cognitive tasks. 16 odorant chemicals will be used for training including: 2 phenyl ethanol, eugenol, lemon, eucalyptus, cinnamon, peppermint, coffee, mandarin, lavender, vanilla, lilac, ginger, chocolate, thyme, banana, and bacon.

Placebo Smell Training (PBO)

Sniffing the same lower intensity odorant chemicals (i.e. N-butanol and 2-phenyl ethanol) over the course of the trial and performing no odor-related cognitive tasks.

Primary outcome measure

  • Change in Psychophysical Olfactory Function from Baseline to 4 and 12 Weeks [ Time Frame: 2 times: 4 weeks, 12 weeks ]
  • Change in Perceived Intensity of Odorants from Baseline to 4 and 12 Weeks [ Time Frame: 2 times: 4 weeks, 12 weeks ]
  • Change in Perceived Hedonics of Odorants from Baseline to 4 and 12 Weeks [ Time Frame: 2 times: 4 weeks, 12 weeks ]
  • Change in Olfactory-related Quality of Life from Baseline to 4 and 12 Weeks [ Time Frame: 2 times: 4 weeks, 12 weeks ]
  • Change in Impact of Olfactory Loss from Baseline to 4 and 12 Weeks [ Time Frame: 2 times: 4 weeks, 12 weeks ]

Central Contacts and Locations

Central contacts

Bernadette M. Cortese, Ph.D.

843-792-6922corteseb@musc.edu

Locations

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Bernadette Cortese, PhD

843-792-6922corteseb@musc.edu

More Information

Sponsor

Medical University of South Carolina

Last update posted

Apr 2, 2026

Last verified

Apr, 2026

Keywords

  • COVID-19
  • Parosmia
  • Hyposmia
  • Anosmia
  • Phantosmia
  • Dysosmia
  • Olfactory Training
  • Neuromodulation
  • Non-invasive Brain Stimulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Medical University of South Carolina on 2026-04-02.