Understanding Non-invasive Vagus Nerve Stimulation Effects in PTSD

Phase 1

Not yet recruiting

• Conditions: PTSD - Post Traumatic Stress Disorder

• Registration Number: NCT06953388
• Lead Sponsor: Wayne State University

Brief Summary

The goal of this study is to determine how non-invasive brain stimulation (delivered through the ear called vagus nerve stimulation) affects fear learning processes in people who have experienced psychological trauma. To answer these questions, we measure bodily responses (heart rate, sweat, startle) and questionnaires. The main questions it aims to answer are:

Does non-invasive vagus nerve stimulation help reduce anxious arousal? Does non-invasive vagus nerve stimulation help dampen learned fear?

Detailed Description

This study aims to determine how non-invasive brain stimulation (delivered through the ear) affects learning processes. During this study, participants who have experienced a trauma will be asked to complete surveys and come to the lab for about 7 hours across four lab visits. Researchers will measure body responses (heart rate, skin conductance, startle), while the ear is stimulated. Participants also will be asked to complete a startle task. The study is at the Wayne State University Tolan Park Research Clinic. Participants will be compensated for their time. To be eligible, participants must be 18-70 years old, have experienced or witnessed a traumatic event, be able to commit 7 hours of time to the study, and be able to wear sensors on their hands, arms, and head and sit quietly at a computer.

Aim 1. Establish feasibility and acceptability of taVNS in a diverse sample of Detroit metro residents with symptoms of posttraumatic stress. It is hypothesized that taVNS delivery will be feasible and acceptable for individuals with trauma exposure and PTS symptoms, and that there will be no difference in acceptability/tolerability between the active and sham conditions.

Aim 2. Establish the effects of active versus sham taVNS on physiological indicators during fear extinction. It is hypothesized that active compared to sham taVNS will a) result in facilitation of fear extinction, and b) show greater modulation of physiological responding. Exploratory Aim: Data will be explored for individual differences (affective blunting, hyperarousal, impaired discrimination of conditioned stimuli) which moderate taVNS effects.

This proposed project will determine how taVNS delivered at higher doses than have been previously administered influence the course of adaptive posttraumatic processing in a sample with trauma exposure, while evaluating the psychophysiological profile in multiple contexts.

Study Timeline

• Study First Submitted: 2025-04-23
• Study First Submitted QC: 2025-04-23
• Status Verified: 2025-05
• Study First Posted: 2025-05-01
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-18
• Study Start: 2026-02-01
• Primary Completion: 2031-01-01
• Study Completion: 2032-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Ages 18-80
2. Fluent in English
3. Experience with a DSM-5 Criterion A trauma (LEC-5)
4. Probable PTSD (PCL-5 ≥ 32)

Exclusion Criteria

1. Visual or Auditory impairment
2. Major injury at time of screen or study procedures
3. Taking ≥20 mg morphine per day
4. Current substance use or intoxication (12-panel drug test)
5. Intellectual disability (MoCA)
6. Self-inflicted injury
7. Occupational injury
8. Prisoner
9. Ongoing domestic violence
10. Pregnant or breastfeeding
11. Contraindications for taVNS

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Fear potentiated startle (FPS)	From enrollment to the end of the cross over visit at week 2	FPS modulation, an objective behavioral indicator of defensive reactivity, is measured during acquisition and extinction, collected using electromyogram (EMG) of the right orbicularis oculi muscle with the EMG module of the Biopac MP160 for Windows.
Skin Conductance (SC)	From enrollment to the end of the cross over visit at week 2	SC is measured using the electrodermal activity (EDA) module of the Biopac system. Two disposable pre-gelled Ag/AgCl electrodes are placed on the hypothenar surface of the non-dominant hand. SCR is defined as the increase from SC during a 1s pre-CS+ onset baseline to SC during the 3-6s post-CS+ onset.
Heart Rate (HR)	From enrollment to the end of the cross over visit at week 2	HR is acquired via electrocardiogram (ECG) Biopac module. Three disposable pre-gelled Ag/AgCl electrodes are used: one each on the right and left sides of the torso, 1cm below the clavicle, and a third on the inside of the left wrist. The HR response is defined as the increase in HR from a 1m baseline prior to the first airblast to 1m after first airblast.
Subjective Units of Distress (SUDS)	From enrollment to the end of the cross over visit at week 2	SUDS is recorded pre- and post- fear acquisition and extinction, and at baseline and recovery. Arousal measures will be evaluated individually and in combination to determine multivariate effects. SUDS and objective responses will be monitored, as investigations show discordance within and between objective and subjective measures of distress.; SUDS are on a scale of 0 (no anxiety/distress, calm and relaxed) to 100 (extreme anxiety/distress, worst ever experienced).
Unconditioned Stimulus Expectancy Ratings	From enrollment to the end of the cross over visit at week 2	Identification of threat/conditioned stimulus with reinforcement (CS+) and safety/conditioned stimulus without reinforcement (CS-) is used to assess US expectancy during fear acquisition and extinction, consistent with mentors', Jovanovic and Norrholm's, research. Individuals respond on a keypad (Cedrus, Inc.) after each trial regarding CS-US contingencies.; Responses consist of 3 button presses (Yes, No, I don't know) for whether participants believe a shape (CS+/CS-) will be followed by the US.

Trial Locations

Locations (1)

Tolan Park Research Clinic, Wayne State University; 🇺🇸 Detroit, Michigan, United States