taVNS, Brain Stimulation
Conditions
Brief summary
This study explores the use of transcutaneous auricular vagus nerve stimulation (taVNS), a new form of neuromodulation which stimulates the ear. 24 healthy subjects without a past medical or psychiatric history will be recruited to participate in a phone screen followed by 1 lab visit. During the lab visit, subjects will participate twice in a validated stress induction technique called the cold pressor test, while concurrently receiving either active or sham taVNS. The cold pressor test consists of subjects placing their feet in an ice bath for a short period of time. Researchers will measure participant's heart rate while they receive taVNS (ear stimulation) and participate in the cold pressor test. Assessments of mood, anxiety, and stress will be collected at the beginning and end of the visit.
Interventions
DEVICEActive taVNS
Electrodes will be attached to the participant's ear with a small sticker or clip, which will deliver mild stimulation. These electrodes will be plugged into the Digitimer DS7a device, which is a device that delivers transcutaneous auricular vagus nerve stimulation or taVNS. Stimulation will be delivered randomly to participant's tragus (the small cartilage knob before the ear canal) for up to 5 minutes while you participate in the stress induction test (by putting both feet into an ice bath).
DEVICESham taVNS
Electrodes will be attached to the participant's ear with a small sticker or clip, which will deliver mild stimulation. These electrodes will be plugged into the Digitimer DS7a device, which is a device that delivers transcutaneous auricular vagus nerve stimulation or taVNS. Stimulation will be delivered randomly to participant's tragus (the small cartilage knob before the ear canal) for up to 5 minutes while you participate in the stress induction test (by putting both feet into an ice bath). During sham (placebo) stimulation, ear electrodes will be attached to the participant's ear but they will not receive any stimulation.
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 18-65 years * English speaking * Non-treatment-seeking community members
Exclusion criteria
* Diagnosis of COVID-19 in the past 14 days * Facial or ear pain or recent ear trauma. * Metal implant devices in the head, heart or neck. * History of brain stimulation or other brain surgery. * History of myocardial infarction or arrhythmia, bradycardia. * Use of B-blockers, antiarrhythmic medication (sodium/potassium/calcium-channel blockers), or blood pressure medications. * Active respiratory disorder. * Personal or family history of seizure or epilepsy or personal use of medications that substantially reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium). * Personal history of head injury, concussion, or self-report of moderate to severe traumatic brain injury. * Individuals suffering from frequent/severe headaches. * Individuals with a reported history of any mental health disorder or taking any psychotropic medications. * Moderate to severe alcohol or substance use disorder. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Heart Rate (Before CPT/taVNS) | Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation) | Heart rate will be measured with EKG electrodes before concurrent stress test and ear stimulation. |
| Mean Heart Rate (During CPT/taVNS) | During concurrent stress test and ear stimulation (average duration of 5 minutes) | Heart rate will be measured with EKG electrodes during concurrent stress test and ear stimulation. |
| Mean Heart Rate (After CPT/taVNS) | After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation) | Heart rate will be measured with EKG electrodes after concurrent stress test and ear stimulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Score of Pain (Before CPT/taVNS) | Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation) | Pain will be assessed using a 0-10 scale (where 0 represents no pain at all and 10 represents the worst pain possible) before concurrent stress test and ear stimulation. |
| Mean Score of Pain (During CPT/taVNS) | During concurrent stress test and ear stimulation (average duration of 5 minutes) | Pain will be assessed using a 0-10 scale (where 0 represents no pain at all and 10 represents the worst pain possible) during concurrent stress test and ear stimulation. |
| Mean Score of Pain (After CPT/taVNS) | After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation) | Pain will be assessed using a 0-10 scale (where 0 represents no pain at all and 10 represents the worst pain possible) after concurrent stress test and ear stimulation. |
| Mean Score of Anxiety (During CPT/taVNS) | During concurrent stress test and ear stimulation (average duration of 5 minutes) | Anxiety will be assessed using a 0-10 scale (where 0 represents no anxiety at all and 10 represents the worst anxiety possible) during concurrent stress test and ear stimulation. |
| Mean Score of Distress (During CPT/taVNS) | During concurrent stress test and ear stimulation (average duration of 5 minutes) | Distress will be assessed using a 0-10 scale (where 0 represents no distress at all and 10 represents the worst distress possible) during concurrent stress test and ear stimulation. |
| Mean Score of Distress (After CPT/taVNS) | After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation) | Distress will be assessed using a 0-10 scale (where 0 represents no distress at all and 10 represents the worst distress possible) after concurrent stress test and ear stimulation. |
| Mean Score of Anxiety (Before CPT/taVNS) | Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation) | Anxiety will be assessed using a 0-10 scale (where 0 represents no anxiety at all and 10 represents the worst anxiety possible) before concurrent stress test and ear stimulation. |
| Mean Score of Anxiety (After CPT/taVNS) | After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation) | Anxiety will be assessed using a 0-10 scale (where 0 represents no anxiety at all and 10 represents the worst anxiety possible) after concurrent stress test and ear stimulation. |
| Mean Score of Distress (Before CPT/taVNS) | Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation) | Distress will be assessed using a 0-10 scale (where 0 represents no distress at all and 10 represents the worst distress possible) before concurrent stress test and ear stimulation. |
Countries
United States
Participant flow
Pre-assignment details
Participants were excluded for any major medical comorbidities, as this study only enrolled healthy neurotypical participants. Upon enrollment, participants were automatically randomized to receive active taVNS or sham stimulation first (all participants received both active and sham, the order was randomized).
Participants by arm
| Arm | Count |
|---|---|
| Active taVNS Then Sham taVNS Participants will receive active then sham (placebo) ear stimulation.
Active taVNS: Electrodes will be attached to the participant's ear with a small sticker or clip, which will deliver mild stimulation. These electrodes will be plugged into the Digitimer DS7a device, which is a device that delivers transcutaneous auricular vagus nerve stimulation or taVNS. Stimulation will be delivered randomly to participant's tragus (the small cartilage knob before the ear canal) for up to 5 minutes while you participate in the stress induction test (by putting both feet into an ice bath).
Sham taVNS: Electrodes will be attached to the participant's ear with a small sticker or clip, which will deliver mild stimulation. These electrodes will be plugged into the Digitimer DS7a device, which is a device that delivers transcutaneous auricular vagus nerve stimulation or taVNS. Stimulation will be delivered randomly to participant's tragus (the small cartilage knob before the ear canal) for up to 5 minutes while you participate in the stress induction test (by putting both feet into an ice bath). During sham (placebo) stimulation, ear electrodes will be attached to the participant's ear but they will not receive any stimulation. | 10 |
| Sham taVNS Then Active taVNS Participants will receive sham (placebo) then active ear stimulation.
Active taVNS: Electrodes will be attached to the participant's ear with a small sticker or clip, which will deliver mild stimulation. These electrodes will be plugged into the Digitimer DS7a device, which is a device that delivers transcutaneous auricular vagus nerve stimulation or taVNS. Stimulation will be delivered randomly to participant's tragus (the small cartilage knob before the ear canal) for up to 5 minutes while you participate in the stress induction test (by putting both feet into an ice bath).
Sham taVNS: Electrodes will be attached to the participant's ear with a small sticker or clip, which will deliver mild stimulation. These electrodes will be plugged into the Digitimer DS7a device, which is a device that delivers transcutaneous auricular vagus nerve stimulation or taVNS. Stimulation will be delivered randomly to participant's tragus (the small cartilage knob before the ear canal) for up to 5 minutes while you participate in the stress induction test (by putting both feet into an ice bath). During sham (placebo) stimulation, ear electrodes will be attached to the participant's ear but they will not receive any stimulation. | 11 |
| Total | 21 |
Baseline characteristics
| Characteristic | Active taVNS Then Sham taVNS | Sham taVNS Then Active taVNS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 21 Participants |
| Age, Continuous | 27.75 years STANDARD_DEVIATION 5.48 | 29 years STANDARD_DEVIATION 5.24 | 28.38 years STANDARD_DEVIATION 5.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 participants | 11 participants | 21 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Mean Heart Rate (After CPT/taVNS)
Heart rate will be measured with EKG electrodes after concurrent stress test and ear stimulation.
Time frame: After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Heart Rate (After CPT/taVNS) | 68.97 beats per minute | Standard Deviation 8.65 |
| Sham taVNS | Mean Heart Rate (After CPT/taVNS) | 68.78 beats per minute | Standard Deviation 9.54 |
Primary
Mean Heart Rate (Before CPT/taVNS)
Heart rate will be measured with EKG electrodes before concurrent stress test and ear stimulation.
Time frame: Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Heart Rate (Before CPT/taVNS) | 72.86 beats per minute | Standard Deviation 10.88 |
| Sham taVNS | Mean Heart Rate (Before CPT/taVNS) | 72.0 beats per minute | Standard Deviation 11.77 |
Primary
Mean Heart Rate (During CPT/taVNS)
Heart rate will be measured with EKG electrodes during concurrent stress test and ear stimulation.
Time frame: During concurrent stress test and ear stimulation (average duration of 5 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Heart Rate (During CPT/taVNS) | 83.54 beats per minute | Standard Deviation 16.24 |
| Sham taVNS | Mean Heart Rate (During CPT/taVNS) | 83.96 beats per minute | Standard Deviation 16.35 |
Secondary
Mean Score of Anxiety (After CPT/taVNS)
Anxiety will be assessed using a 0-10 scale (where 0 represents no anxiety at all and 10 represents the worst anxiety possible) after concurrent stress test and ear stimulation.
Time frame: After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Anxiety (After CPT/taVNS) | 0.48 units on a scale | Standard Deviation 0.75 |
| Sham taVNS | Mean Score of Anxiety (After CPT/taVNS) | 0.62 units on a scale | Standard Deviation 0.92 |
Secondary
Mean Score of Anxiety (Before CPT/taVNS)
Anxiety will be assessed using a 0-10 scale (where 0 represents no anxiety at all and 10 represents the worst anxiety possible) before concurrent stress test and ear stimulation.
Time frame: Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Anxiety (Before CPT/taVNS) | 1.43 units on a scale | Standard Deviation 1.72 |
| Sham taVNS | Mean Score of Anxiety (Before CPT/taVNS) | 1.81 units on a scale | Standard Deviation 1.75 |
Secondary
Mean Score of Anxiety (During CPT/taVNS)
Anxiety will be assessed using a 0-10 scale (where 0 represents no anxiety at all and 10 represents the worst anxiety possible) during concurrent stress test and ear stimulation.
Time frame: During concurrent stress test and ear stimulation (average duration of 5 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Anxiety (During CPT/taVNS) | 3.52 units on a scale | Standard Deviation 2.77 |
| Sham taVNS | Mean Score of Anxiety (During CPT/taVNS) | 3.48 units on a scale | Standard Deviation 2.27 |
Secondary
Mean Score of Distress (After CPT/taVNS)
Distress will be assessed using a 0-10 scale (where 0 represents no distress at all and 10 represents the worst distress possible) after concurrent stress test and ear stimulation.
Time frame: After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Distress (After CPT/taVNS) | 0.05 units on a scale | Standard Deviation 0.22 |
| Sham taVNS | Mean Score of Distress (After CPT/taVNS) | 0.14 units on a scale | Standard Deviation 0.36 |
Secondary
Mean Score of Distress (Before CPT/taVNS)
Distress will be assessed using a 0-10 scale (where 0 represents no distress at all and 10 represents the worst distress possible) before concurrent stress test and ear stimulation.
Time frame: Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Distress (Before CPT/taVNS) | 0.29 units on a scale | Standard Deviation 1.1 |
| Sham taVNS | Mean Score of Distress (Before CPT/taVNS) | 0.33 units on a scale | Standard Deviation 1.15 |
Secondary
Mean Score of Distress (During CPT/taVNS)
Distress will be assessed using a 0-10 scale (where 0 represents no distress at all and 10 represents the worst distress possible) during concurrent stress test and ear stimulation.
Time frame: During concurrent stress test and ear stimulation (average duration of 5 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Distress (During CPT/taVNS) | 4.52 units on a scale | Standard Deviation 3.04 |
| Sham taVNS | Mean Score of Distress (During CPT/taVNS) | 4.48 units on a scale | Standard Deviation 3.01 |
Secondary
Mean Score of Pain (After CPT/taVNS)
Pain will be assessed using a 0-10 scale (where 0 represents no pain at all and 10 represents the worst pain possible) after concurrent stress test and ear stimulation.
Time frame: After concurrent stress test and ear stimulation (up to 10 minutes after concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Pain (After CPT/taVNS) | 0.24 units on a scale | Standard Deviation 0.44 |
| Sham taVNS | Mean Score of Pain (After CPT/taVNS) | 0.10 units on a scale | Standard Deviation 0.3 |
Secondary
Mean Score of Pain (Before CPT/taVNS)
Pain will be assessed using a 0-10 scale (where 0 represents no pain at all and 10 represents the worst pain possible) before concurrent stress test and ear stimulation.
Time frame: Baseline (up to 10 minutes prior to concurrent stress test and ear stimulation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Pain (Before CPT/taVNS) | 0.05 units on a scale | Standard Deviation 0.22 |
| Sham taVNS | Mean Score of Pain (Before CPT/taVNS) | 0 units on a scale | Standard Deviation 0 |
Secondary
Mean Score of Pain (During CPT/taVNS)
Pain will be assessed using a 0-10 scale (where 0 represents no pain at all and 10 represents the worst pain possible) during concurrent stress test and ear stimulation.
Time frame: During concurrent stress test and ear stimulation (average duration of 5 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active taVNS | Mean Score of Pain (During CPT/taVNS) | 5.67 units on a scale | Standard Deviation 2.39 |
| Sham taVNS | Mean Score of Pain (During CPT/taVNS) | 5.62 units on a scale | Standard Deviation 2.11 |