Study of Chemosensory Enhancement Through Neuromodulation Training (SCENT for Long COVID)

NCT05855369 | Recruiting Phase 2 DMC

• 2 other identifiers: Pro00127790R01DC021179
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Change in Psychophysical Olfactory Function from Baseline to 4 and 12 Weeks

  Sniffin' Sticks (Bughardt Messtechnik, Wedel Germany) will be used to determine odor threshold (T), odor discrimination (D), and odor identification (I), each on 16-point scales, and summed for a total TDI score. Higher scores indicate better function.

  2 times: 4 weeks, 12 weeks

• Change in Perceived Intensity of Odorants from Baseline to 4 and 12 Weeks

  Perceived intensity on 100-mm visual analog scales with anchor points: 0="imperceptible" to 100="extremely intense" will be rated for suprathreshold concentrations of PEA, vanilla, eugenol, and eucalyptus.

  2 times: 4 weeks, 12 weeks

• Change in Perceived Hedonics of Odorants from Baseline to 4 and 12 Weeks

  Perceived hedonics on 100-mm visual analog scales with anchor points: 0="extremely unpleasant" to 100="extremely pleasant".

  2 times: 4 weeks, 12 weeks

• Change in Olfactory-related Quality of Life from Baseline to 4 and 12 Weeks

  The Modified Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) consists of 17 negative statements (rated on a scale from 0 to 3; total score ranging from 0 to 51), with lower scores indicating better olfactory-related quality of life.

  2 times: 4 weeks, 12 weeks

• Change in Impact of Olfactory Loss from Baseline to 4 and 12 Weeks

  The Impact of Olfactory Loss Visual Analog Scale (IOL-VAS) consists of 9 separate items assessing the impact of olfactory loss upon mood, food enjoyment, social interactions, safety, hygiene, sex, cooking, appetite, and weight changes, rated from 0 (no impact) to 10 (biggest impact possible).

  2 times: 4 weeks, 12 weeks

Secondary Outcomes (8)

• Change in Long COVID Symptoms from Baseline to 4 and 12 Weeks

  2 times: 4 weeks, 12 weeks

• Change in Sustained Attention from Baseline to 4 and 12 Weeks

  2 times: 4 weeks, 12 weeks

• Change in Cognitive Function from Baseline to 4 and 12 Weeks

  2 times: 4 weeks, 12 weeks

• Change in Mood State from Baseline to 4 and 12 Weeks

  2 times: 4 weeks, 12 weeks

• Change in Sleep Quality from Baseline to 4 and 12 Weeks

  2 times: 4 weeks, 12 weeks

Other Outcomes (5)

• Treatment Feasibility, Acceptability, and Fidelity at 4 and 12 weeks

  2 times: 4 weeks, 12 weeks

• Durability of Treatment on Subjective Olfactory Function at the 6-month Follow Up

  1 time: 6 months

• Durability of Treatment on Long COVID Symptoms at the 6-month Follow Up

  1 time: 6 months

Study Arms (3)

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

ACTIVE COMPARATOR

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

Device: Trigeminal Nerve Stimulation (TNS); Other: Active Smell Training (ST)

Active Smell Training (ST)

ACTIVE COMPARATOR

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

Other: Active Smell Training (ST)

Placebo Smell Training (PBO)

PLACEBO COMPARATOR

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

Other: Placebo Smell Training (PBO)

Interventions

Trigeminal Nerve Stimulation (TNS) DEVICE

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.

Also known as: Transcutaneous Electrical Nerve Stimulation

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

Active Smell Training (ST) OTHER

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.

Also known as: Olfactory Training

Active Smell Training (ST); Combination Trigeminal Nerve Stimulation (TNS) and active Smell Training (ST)

Placebo Smell Training (PBO) OTHER

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.

Placebo Smell Training (PBO)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator
• Medical University of South Carolina: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Olfaction Disorders; Post-Acute COVID-19 Syndrome; COVID-19; Anosmia

Interventions

Transcutaneous Electric Nerve Stimulation; Olfactory Training

Condition Hierarchy (Ancestors)

Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Central Study Contacts

Bernadette M. Cortese, Ph.D.

CONTACT

843-792-6922; corteseb@musc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: A separate outcomes assessor, blind to treatment intervention for all participants, will perform all clinician-administered primary outcomes (i.e. olfactory function determined by Sniffin' Sticks, ratings for odor intensity/hedonics, clinician-administered assessment of cognitive function, and the clinical global impressions for smell dysfunction). This outcomes assessor will not be involved with any other aspects of the trial. Additionally, the participant will be blind to ST versus PBO group assignment, but not TNS+ST assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: May 11, 2023
• Study Start: October 2, 2023
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD will be shared after the primary data analyses are complete and our final findings are published.
• Access Criteria: Information on where the data will be available and how to access it will be published with all publications/presentations that come from this study

Locations

US (1)