Clinical trial NCT05855369: Study of Chemosensory Enhancement Through Neuromodulation Training (SCENT for Long COVID)
Official title: A Randomized Controlled Trial of Smell Training and Trigeminal Nerve Stimulation in the Treatment of COVID-related Persistent Smell Loss
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Smell Dysfunction
Olfactory Disorder
Long COVID
Keywords: COVID-19
Parosmia
Hyposmia
Anosmia
Phantosmia
Dysosmia
Olfactory Training
Neuromodulation
Non-invasive Brain Stimulation
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Deafness and Other Communication Disorders (NIDCD)
First posted: 2023-05-11
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Sudden smell loss (SL), a hallmark feature of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-coV-2/COVID), frequently persists well past the initial recovery; rates of unresolved anosmia (total loss) are 21%, with unresolved hyposmia (reduced smell) or parosmia (distorted smell) higher at nearly 50%. SL is now recognized as a core symptom of "long COVID" (LC), which also includes other impairments in mood, cognition, and sleep. Given that SL itself can negatively impact many of the same problems being recognized in the symptomatology of LC, it is likely that SL is both a symptom of LC and a contributing factor that worsens other LC symptoms (i.e. mood, cognition, sleep, etc.). As such, successful treatment of SL could also help to improve these other LC symptoms.

Smell/olfactory training (ST) is currently being studied as a treatment for COVID-related 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. However, its limitations include the burden of many months of daily practice that often leads to sub-optimal compliance and dropout.

The current study aims to determine whether the benefits of ST can be accelerated and enhanced by using a novel, adjunct neuromodulatory intervention to conventional ST. 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. Prior work demonstrated TNS-enhanced psychophysical detection of odorants. Yet the effects of TNS are extensive, i.e. improved executive functioning (e.g. attention), sleep quality, and daytime sleepiness, as well as therapeutic efficacy across a number of neuropsychiatric disorders. Thus, TNS-as an adjunct to ST-may not only improve overall efficacy and speed of recovery of SL, but may help to treat some of the other symptoms of LC that ST, and improvement in smell function, may not fully resolve.

This randomized, controlled trial (RCT) of ST and combination TNS and ST in adults with COVID-related SL will use a 3- group design: Group 1) Active ST (N=60), Group 2) Placebo ST (PBO, N=60), and Group 3) Active TNS plus Active ST (N=60). Our primary objectives are to 1) determine the efficacy of ST versus potential natural gains in function, 2) determine the TNS-enhanced effects of ST on SL, and 3) determine whether TNS+ST is more efficacious than ST in treating the other symptoms of LC.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Psychophysical Olfactory Function from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Perceived Intensity of Odorants from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Perceived Hedonics of Odorants from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Olfactory-related Quality of Life from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Impact of Olfactory Loss from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
Secondary outcomes:
measure: Change in Long COVID Symptoms from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Sustained Attention from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Cognitive Function from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Mood State from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Sleep Quality from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Excessive Daytime Sleepiness from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Symptoms of Depression from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Change in Symptoms of Anxiety from Baseline to 4 and 12 Weeks
timeFrame: 2 times: 4 weeks, 12 weeks
Other outcomes:
measure: Treatment Feasibility, Acceptability, and Fidelity at 4 and 12 weeks
timeFrame: 2 times: 4 weeks, 12 weeks
measure: Durability of Treatment on Subjective Olfactory Function at the 6-month Follow Up
timeFrame: 1 time: 6 months
measure: Durability of Treatment on Long COVID Symptoms at the 6-month Follow Up
timeFrame: 1 time: 6 months
measure: Durability of Treatment on Mood at the 6-month Follow Up
timeFrame: 1 time: 6 months
measure: Durability of Treatment on Sleepiness and Sleep Quality at the 6-month Follow Up
timeFrame: 1 time: 6 months
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References: