Study of Chemosensory Enhancement Through Neuromodulation Training (SCENT): Open Label

Smell dysfunction significantly impacts quality of life and safety, with limited effective treatments. This open-label study evaluates the preliminary efficacy of combining non-invasive trigeminal nerve stimulation (TNS) with standard smell training (ST) to improve olfactory function. Participants will complete 8 weeks of at-home treatment and attend three in-person visits for assessment. Improvements in smell, mood, sleep, and quality of life will be measured.

Study Overview

• Status: Not yet recruiting
• Conditions: Olfactory Impairment
• Intervention / Treatment: Combination product: Trigeminal Nerve Stimulation-enhanced Smell Training

Detailed Description

Smell dysfunction is a serious health issue associated with everyday dangers like the inability to correctly identify nearby hazards (e.g. burning, gas leaks, or spoiled food), psychosocial problems including social withdrawal and reduced quality and enjoyment of life, a myriad of psychiatric conditions, and a generally increased risk of mortality. Further escalating the gravity of olfactory dysfunction is mounting evidence of olfactory disturbance as prodromal to neurodegenerative disorder.

Smell/olfactory training (ST) has emerged as the first-line, and only (current) treatment for smell loss (SL). Classic ST requires twice daily practice of sniffing odorants over the course of 3 months to regenerate olfactory neurons, engage smell-related cognitive functions, and retrain the brain to smell. ST is promising as a stand-alone treatment for SL. However, limitations of ST include the burden of many months of daily practice that leads to sub-optimal compliance, dropout and modest effect sizes. Methods to accelerate and enhance the benefits of ST are needed.

The olfactory and intranasal trigeminal circuits are structurally and functionally coupled brain systems, both essential to smell function. In fact, there is widespread central overlap and convergence of these systems that is believed to underlie the strong mutual, inhibitory influence between the odor-processing functions of the olfactory pathway and the pungency-processing functions of the trigeminal pathway. Given the convergence and functional influence the circuits have on one another, it is likely that the trigeminal system can be leveraged to activate or enhance olfaction. As such, a method that directly engages the intranasal trigeminal system may be an effective strategy to improve olfactory function.

Trigeminal nerve stimulation (TNS) is a non-invasive, pain-free, method of neuromodulation that delivers low levels of electrical stimulation to the trigeminal circuit, having potential to enhance smell function through activation of the highly connected olfactory-intranasal trigeminal systems. The study investigator's previously published work demonstrated TNS-enhanced psychophysical detection of odorants in healthy adults. The TNS device is FDA 510(k)-cleared for the at-home treatment of pain and attention deficit hyperactivity disorder (ADHD); however, its use in this study is to enhance olfactory function.

For this study, the study investigators will conduct an at-home, open label trial of TNS-enhanced ST in adults. The primary objectives are to determine initial efficacy of TNS-enhanced ST at treating smell loss. Objectives will be achieved through the following aims:

Aim 1: Determine the effects of TNS-enhanced ST on olfactory deficits. The study investigators hypothesize that 8 weeks of TNS-enhanced ST will show significant improvement in psychophysical and subjective olfactory function at 8 weeks compared to baseline.

Aim 2: Determine if TNS-enhanced ST improve other symptoms associated with smell loss. The study investigators hypothesize that 8 weeks of TNS-enhanced ST will show significant improvement in mood, sleep and quality of life at 8 weeks compared to baseline.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
      • Contact: Bernadette Cortese, Ph.D.; Phone Number: 843-792-6922; Email: corteseb@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80
• Self-reported or medically documented smell loss
• Treatment-seeking for their smell loss
• Naïve to TNS
• Able to comprehend English and provide informed consent

Exclusion Criteria:

• Medical Records not available to confirm eligibility
• Documented/Suspected head injury (e.g. sport, accident, blast exposure)
• Neurological disorder (e.g. epilepsy, neurodegenerative disorder)
• Serious mental illness (e.g. schizophrenia, bipolar disorder)
• Suicidal ideation within the last month
• Current (≤6 months) and/or heavy cigarette smokers (i.e. ≥ 10 pack-years)
• Oral/nasal steroids or other intranasal medications
• Immunomodulatory medications
• Pregnant or trying to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Open Label Trigeminal Nerve Stimulation-enhanced Smell Training (TNS-enhanced ST); TNS-enhanced ST will be administered at-home 5 days/week for 8 weeks. Participants will self-administer the first treatment of TNS-enhanced ST with the assistance and help of study staff. This includes attaching the gel pads to the forehead and turning the TNS system on for 30-min., training with different odorants and providing ratings on a website called REDCap, an easy-to-use, secure, internet-based data collection site.

Combination product: Trigeminal Nerve Stimulation-enhanced Smell Training; TNS is a form of cranial nerve stimulation that uses a simple transcutaneous electrical nerve stimulation device, and adhesive electrodes that are attached to forehead to deliver low-level electrical current. Stimulating the trigeminal nerve activates the trigeminal afferent sensory pathway and central brain regions where the intranasal trigeminal and olfactory circuits converge. Smell Training requires 4 odors to be smelled individually for 10 sec each and record ratings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Psychophysical Olfactory Function from Baseline to 4 and 8 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.	8 weeks
Change in Perceived Intensity of Odorants from Baseline to 4 and 8 Weeks	Perceived intensity on 100-mm visual analog scales with anchor points: 0="imperceptible" to 100="extremely intense".	8 weeks
Change in Perceived Hedonics of Odorants from Baseline to 4 and 8 Weeks	Perceived hedonics on 100-mm visual analog scales with anchor points: 0="extremely unpleasant" to 100="extremely pleasant".	8 weeks
Change in Olfactory-related Quality of Life from Baseline to 4 and 8 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.	8 weeks
Change in Impact of Olfactory Loss from Baseline to 4 and 8 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).	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mood State from Baseline to 4 and 8 Weeks	The Profile of Mood States Short Form (POMS-SF) is a psychological rating scale used to assess transient, distinct mood states across six different dimensions including Tension or Anxiety, Anger or Hostility, Vigor or Activity, Fatigue or Inertia, Depression or Dejection, and Confusion or Bewilderment.	8 weeks
Change in Sleep Quality from Baseline to 4 and 8 Weeks	The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components that produce one global score. Scores greater than 5 are indicative of a sleep disturbance.	8 weeks
Change in Symptoms of Depression from Baseline to 4 and 8 Weeks	The Patient Health Questionnaire-9 (PHQ-9) is a self-administered 9-item questionnaire to screen for the presence and severity of depression. Items are rated on a 3pt scale ranging from 0="Not at all" to 3="Nearly every day". Total score ranges from 0-27 and is used to classify depression severity: 0-4=None/Minimal; 5-9=Mild; 10-14=Moderate; 15-19=Moderately Severe; 20-27=Severe.	8 weeks
Change in Symptoms of Anxiety from Baseline to 4 and 8 Weeks	The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item questionnaire to screen for presence and severity of anxiety disorder. Items are rated on a 3pt scale ranging from 0="Not at all" to 3="Nearly every day". Total score ranges from 0 to 21 and is used to classify anxiety severity: 0-4 (minimal anxiety), 5-9 (mild anxiety), 10-14 (moderate anxiety), 15-21 (severe anxiety).	8 weeks

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Estimated): July 8, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: chronic rhinosinusitis; trigeminal nerve stimulation; olfaction; olfactory dysfunction; smell loss; olfactory training; sensory loss; smell training
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Sensation Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anosmia; Olfaction Disorders
• Other Study ID Numbers: Pro00151125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No