# A randomized controlled trial of smell training and trigeminal nerve stimulation in the treatment of COVID-related persistent smell loss

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $625,742

## Abstract

ABSTRACT
COVID exposed the critical need for new and improved treatment interventions for chemosensory (i.e. smell and
taste) dysfunction. Evidence indicates that COVID-related smell loss (SL) often endures well past recovery of
the initial infection and is highly associated with other long COVID neuropsychiatric symptoms including
impairments in mood, sleep, and cognition. To date, there are few interventions available to treat COVID-related
persistent SL and its related impairments. While smell/olfactory training (ST) has emerged as a widely
prescribed, front-line treatment for COVID-related persistent SL, rigorous study is required to determine its
efficacy in long COVID. Moreover, given that ST is a lengthy treatment, requiring 12 weeks or longer of training,
and is associated with slow improvement, non-compliance, drop-out, and modest effect size, additional study of
adjunctive methods to improve its efficacy and speed of recovery are warranted. Here we propose the first study
to investigate combinatorial trigeminal nerve stimulation (TNS) and ST in the treatment of post-COVID persistent
SL and associated deficits in mood, sleep and cognitive impairment. Our previous work suggests that TNS, an
easy-to-use and very safe form of non-invasive brain stimulation, increases olfactory sensitivity and has the
potential to improve other symptoms of long COVID including mood, daytime sleepiness, and attention.
Therefore, we will conduct a larger at-home, randomized, controlled trial of ST and determine whether TNS
enhances the effects of ST in adults with COVID-related persistent SL. Our primary objectives are 1) to determine
the efficacy of ST, compared to any natural gain in function, on olfactory-specific deficits (active ST versus sham
ST), 2) to determine the TNS-enhanced effects of ST on olfactory-specific deficits (active TNS+ST versus active
ST), and 3) to determine if TNS+ST, compared to ST, is also more efficacious in the treatment of other
impairments (i.e. mood, sleep, and cognitive) associated with both SL and long COVID. While this research is
focused on COVID-related persistent SL, the results will provide the necessary information to extend the study
and use of ST and TNS to address wider chemosensory dysfunction. This line of investigation has the potential
to make a substantial impact on how chemosensory dysfunction is treated and in turn significantly improve the
current standard of care.

## Key facts

- **NIH application ID:** 10852935
- **Project number:** 5R01DC021179-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Bernadette Cortese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $625,742
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852935

## Citation

> US National Institutes of Health, RePORTER application 10852935, A randomized controlled trial of smell training and trigeminal nerve stimulation in the treatment of COVID-related persistent smell loss (5R01DC021179-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10852935. Licensed CC0.

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