Effect of Transcutaneous Auricular Neurostimulation on Cognitive Performance in a Laboratory Model of Acute Stress Reaction

Cognitive Performance Clinical Trial

— ASR  

Official title:

Effect of Transcutaneous Auricular Neurostimulation on Cognitive Performance in a Laboratory Model of Acute Stress Reaction

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06390267
• Other study ID #: SBM-ASR-01
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2024
• Est. completion date: April 30, 2025

Study information

• Verified date: April 2024
• Source: Spark Biomedical, Inc.
• Contact: Caroline Benner
• Phone: 817-933-2727
• Email: caroline.benner[@]sparkbiomedical.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to test the effects of transcutaneous auricular neurostimulation (tAN) in treating or preventing performance degradation after an acute stressor.

Description:

This study is designed as a randomized, double-blind, sham-controlled trial. Sixty healthy, able-bodied participants will be randomized 1:1:2:2 into one of four experimental groups: Group 1: Active tAN for prophylactic treatment prior to acute stress exposure (N=10) Group 2: Sham stimulation for prophylactic treatment prior to acute stress exposure (N=10) Group 3: Active tAN for acute treatment during acute stress exposure (N=20) Group 4: Sham stimulation for acute treatment during acute stress exposure (N=20) Participants will complete a baseline performance of three tasks. tAN treatment will then be administered prior to or during an acute stress test. Participants will complete the same three tasks preformed at baseline. In addition to the tAN therapy earpiece, subjects will have biosensors attached to them to collect biomarker information.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 41 Years

Eligibility

Inclusion Criteria:

1. Adults 18 to 41 years old

2. Participant has the cognitive and physical abilities to carry out the study tasks

3. Participant is right-hand dominant

4. Proficient in the English language

5. Ability to understand the explanations and instructions given by the study personnel

Exclusion Criteria:

1. Participant presents current evidence of an uncontrolled and/or clinically significant medical condition or psychiatric condition

2. Participant has used any psychological stress-management intervention within the last 4 weeks

3. Participant is participating in another interventional trial within 90 days prior to or throughout duration of trial

4. Participant has a prior diagnosis of post-traumatic stress disorder, acute stress disorder, or generalized anxiety disorder

5. Participant is currently using anti-anxiety medications such as Xanax or beta blockers

6. Participant has a diagnosis of attention deficit hyperactivity disorder (ADHD) and/or is currently taking medications for the treatment of ADHD.

7. History of substance abuse or drug dependence including nicotine and alcohol in the past 3 months

8. Participant has abnormal ear anatomy, ear infection present, or earpiercing that could interfere with stimulation

9. Participant has a history of epileptic seizures

10. Participant has a history of neurologic diseases or traumatic brain injury

11. Participant wears or utilized other devices that cannot be removed during the study (e.g., pacemakers, cochlear prostheses, neurostimulators)

12. Females who are pregnant or lactating

13. Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants are risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

Related Conditions & MeSH terms

• Acute Stress Reaction
• Cognitive Performance
• Fractures, Stress
• Stress Disorders, Traumatic, Acute

Intervention

Device:
• Sparrow Hawk (Active)
Wearable, battery-operated, device designed to transcutaneously stimulate nerves on and/or around the auricle. The device will be used to deliver tAN sessions of active (prophylactic or acute) therapy according to the participant's randomization group.
• Sparrow Hawk (Sham)
Wearable, battery-operated, device designed to transcutaneously stimulate nerves on and/or around the auricle. The device will be used to deliver tAN sessions of sham (prophylactic or acute) therapy according to the participant's randomization group.

Locations

Country	Name	City	State
United States	Battelle Memorial Institute	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Spark Biomedical, Inc.	Battelle Memorial Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in heart rate variability in milliseconds (ms) across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in heart rate in beats per minute (bpm) across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in electrodermal activity across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in cortisol levels across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in Interleukin-6 (IL-6) levels across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in melatonin levels across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in Tumor Necrosis Factor Alpha (TNF-a) levels across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable)	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in electroencephalogram (EEG) across groups	Collection of biomarker data will be collected via wearable sensors throughout the study and saliva sample collection during post-assessment. Biosensors include 3 off-the-shelf wearables (Empatica E4 watch, g.tec g.HIamp RESEARCH 80 channels with g.GAMMAcap2 Dry Electrode EEG System, and the Corti Wearable). EEG signals are analyzed across different frequency bands, including delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (>30 Hz).	From baseline, during the stressor, and post-stressor (up to 3 hours)
Other	Change in self-reported stress across groups using the Stress Monitoring and Response Tool (SMART)	The SMART tool is a patient-reported assessment of acute stress. The questionnaire contains questions asking the participant to rate their severity of stress related symptoms on a scale of 0 ("none") to 10 ("severe"). Symptoms include feeling worthless, sad, distant, irritable, headaches, dizziness, fatigue, nausea, difficulty concentrating, pain, etc. This study will ask participants 23 questions on the SMART tool based on their recent experiences.	Before baseline to after post-stressor tasks (up to 3 hours; assessment valid up to 24 hours after event))
Other	Mean therapeutic stimulation intensity	amplitude in milliamperes (mA)	From start to end of tAN (30 minutes)
Primary	Match-to-Sample Task (MST)	Mean change in performance on the MST (in combination with the Psychomotor Vigilance Task (PVT) and Perdue Pegboard Task (PPT)) in the active tAN acute treatment group (Group 3) compared to sham acute treatment group (Group 4). The MST assesses short-term spatial memory (working memory) and pattern recognition skills. An 8 × 8 matrix of a red and green checkerboard pattern will be presented for 10 seconds, then removed, and then followed by a variable delay of 8 or 16 seconds. Two matrices will then be presented: the original matrix and a matrix with the color of 2 squares reversed. The subjects will attempt to select the original matrix. The task consists of 30 trials, ˜15 for each delay. A response (left or right arrow key) is required within 10 s, or a time-out error will be recorded. Correct matches were recorded, as was reaction time. This test takes less than 5 minutes to complete.	From baseline to post-stressor (up to 3 hours)
Primary	Psychomotor Vigilance Task (PVT)	Mean change in performance on the PVT (in combination with the MST and PPT) in the active tAN acute treatment group (Group 3) compared to sham acute treatment group (Group 4). The PVT is a test of visual reaction time. A series of stimuli are presented at random intervals on a screen, and the subject responds as rapidly as possible when a stimulus appears. Response time, false alarms, and the number of lapses (long duration responses) will be recorded. Performance lapses refer to the instances when a subject failed to respond in <500 ms. This test will be administered on a computer monitor or tablet.	From baseline to post-stressor (up to 3 hours)
Primary	Perdue Pegboard Task (PPT)	Mean change in performance on the PTT (in combination with the PVT and MST) in the active tAN acute treatment group (Group 3) compared to sham acute treatment group (Group 4). The PPT is a psychomotor test of manual dexterity and bimanual coordination. A pegboard consisting of two parallel sets of twenty-five holes arranged vertically is presented to the participant, and they are asked to remove pegs from concave cups at the top of the board and place them in the holes sequentially as rapidly as possible. The number of pegs placed successfully in thirty seconds is scored. Each participant is tested three times using both hands.	From baseline to post-stressor (up to 3 hours)
Primary	Maastricht Acute Stress Test (MAST)	The MAST is a safe, non-invasive, and expedited method to create a stress response in human subjects under laboratory conditions. The test combines two well-validated laboratory stress paradigms, the Trier Social Stress Test (TSST) and the Cold Pressor Test (CPT) into a single protocol. The MAST is effective in increasing salivary cortisol, increasing blood pressure, salivary alpha-amylase, and eliciting subjective stress reactions. Participants will be videotaped and monitored to analyze their facial expressions. They will undergo multiple hand immersion trials (HIT) in which they have to immerse their hand in ice-cold (2 °C) water. They will engage in mental arithmetic trials (MAT), counting backwards starting at 2043 in steps of 17 as fast and accurate as possible. For each mistake made, the experimenter will provide negative feedback and instruct them to start over at 2043.	After baseline tasks, approximately 35 minutes
Secondary	Mean change in performance on the MST in the active tAN groups (Groups 1 and 3) compared to sham groups (Groups 2 and 4).	Mean change in performance on the MST in combination with PVT and PPT	From baseline to post-stressor (up to 3 hours)
Secondary	Mean change in performance on the PVT in the active tAN groups (Groups 1 and 3) compared to sham groups (Groups 2 and 4).	Mean change in performance on the PVT in combination with MST and PPT	From baseline to post-stressor (up to 3 hours)
Secondary	Mean change in performance on the PPT in the active tAN groups (Groups 1 and 3) compared to sham groups (Groups 2 and 4).	Mean change in performance on the PPT in combination with MST and PVT	From baseline to post-stressor (up to 3 hours)
Secondary	Mean change in performance on the MTS in the prophylactic active tAN group (Group 1) compared to the acute active tAN group (Group 3).	Mean change in performance on the MST in combination with PVT and PPT	From baseline to post-stressor (up to 3 hours)
Secondary	Mean change in performance on the PVT in the prophylactic active tAN group (Group 1) compared to the acute active tAN group (Group 3).	Mean change in performance on the PVT in combination with MST and PPT	From baseline to post-stressor (up to 3 hours)
Secondary	Mean change in performance on the PPT in the prophylactic active tAN group (Group 1) compared to the acute active tAN group (Group 3).	Mean change in performance on the PPT in combination with MST and PVT	From baseline to post-stressor (up to 3 hours)
Secondary	Change in working memory as measured by performance on the MST		From baseline to post-stressor (up to 3 hours)
Secondary	Change in reaction time as measured by performance on the PVT		From baseline to post-stressor (up to 3 hours)
Secondary	Change in dexterity as measured by performance on the PPT		From baseline to post-stressor (up to 3 hours)