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

ConditionsSmell Dysfunction Olfactory Disorder Long COVID

Trial statusRecruiting

Trial phasePhase 2, Phase 3

Trial typeInterventional

Biological sexAll

Age18-65

SponsorMedical University of South Carolina

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

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.
Active Smell Training (ST)
Other intervention
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.
Placebo Smell Training (PBO)
Other intervention
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.

Treatment groups

145 Participants

are divided into 3 treatment groups

Group A: Combination Trigeminal Nerve Stimulation (TNS) and active Smell Training (ST)Active comparator 2 interventions

Group B: Active Smell Training (ST)Active comparator 1 intervention

Group C: Placebo Smell Training (PBO)Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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".

Time frame

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.

Time frame

2 times: 4 weeks, 12 weeks

Secondary outcomes

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

53 long COVID symptoms (scored from 0-53 reflecting the number of different symptoms experienced) and the impact of those symptoms (scored from 0=no impact to 10=maximal impact) will be obtained.

Time frame

2 times: 4 weeks, 12 weeks

Change in Sustained Attention from Baseline to 4 and 12 Weeks

The Sustained Attention to Response Task (SART) is a computer-based go/no-go task that requires participants to withhold behavioral response to a single, infrequent target (often the digit 3) presented amongst a background of frequent non-targets (0-2, 4-9).

Time frame

2 times: 4 weeks, 12 weeks

Change in Cognitive Function from Baseline to 4 and 12 Weeks

The NIH Toolbox Cognitive Battery is a widely used assessment for detecting cognitive impairment. This test assesses short-term memory, executable performance, attention, and focus.

Time frame

2 times: 4 weeks, 12 weeks

Change in Mood State from Baseline to 4 and 12 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

2 times: 4 weeks, 12 weeks

Other outcomes

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

Quantitative measurements will include the number of 1) sessions completed (completion rate), 2) technical problems, 3) adverse events, 4) study drop-out, and 5) the number of study-issued treatment cases returned at the end of treatment. The Feasibility of Intervention Measure (FIM) and the Acceptability of Intervention Measure (AIM) will be used. Both the FIM and AIM contain 4 items that are scored on a 5-point scale (1=completely disagree to 5=completely agree). Responses are averaged across the 4 items, with a score of 4 or more indicating adequate feasibility and acceptability of an intervention. Fidelity (i.e. adherence) that the treatment is delivered as intended will be measured by study staff who will rate adherence on a 5-point scale (1=little to 5=complete). Qualitative data using open-ended questions regarding the nature of any technical problems and the reasons for missed treatment sessions will be assessed.

Time frame

2 times: 4 weeks, 12 weeks

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

Subjective function will be assessed with the QOD-NS and IOL-VAS.

Time frame

1 time: 6 months

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

53 long COVID symptoms (scored from 0-53 reflecting the number of different symptoms experienced) and the impact of those symptoms (scored from 0=no impact to 10=maximal impact) will be obtained.

Time frame

1 time: 6 months

Durability of Treatment on Mood at the 6-month Follow Up

Mood will be assessed with the PHQ-9, GAD-7, and POMS-SF

Time frame

1 time: 6 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Medical University of South Carolina

Lead sponsor

National Institutes of Health (NIH)

Collaborator

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Source ClinicalTrials.gov

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