A Phase 2 interventional study of Trigeminal Nerve Stimulation-enhanced Smell Training in Olfactory Impairment, sponsored by Medical University of South Carolina. Recruiting at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-12.
Sponsored by Medical University of South Carolina · Phase 2, Interventional, and Treatment
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.
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.
70 studies on the registry are indexed under Olfaction Disorders; 18 are open to participants now.
This study's planned enrollment of 60 is close to the median of 60 across 49 interventional studies indexed under Olfaction Disorders.
Browse Olfaction Disorders studies →Medical University of South Carolina is the lead sponsor of 874 studies on the registry; 166 are open to participants now.
Of its 131 completed or terminated interventional studies of FDA-regulated products, 104 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
Time frame: 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".
Time frame: 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".
Time frame: 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.
Time frame: 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).
Time frame: 8 weeks
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 8 weeks
Plan to share: Undecided
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Medical University of South Carolina →