Understanding Non-invasive Vagus Nerve Stimulation Effects in PTSD

NCT06953388 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: IRB-23-05-5811
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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?

Conditions

PTSD - Post Traumatic Stress Disorder

Keywords

PTSD; brain stimulation; fear learning; autonomics; fear potentiated startle

Outcome Measures

Primary Outcomes (5)

• Fear potentiated startle (FPS)

  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.

  From enrollment to the end of the cross over visit at week 2

• Skin Conductance (SC)

  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.

  From enrollment to the end of the cross over visit at week 2

• Heart Rate (HR)

  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.

  From enrollment to the end of the cross over visit at week 2

• Subjective Units of Distress (SUDS)

  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).

  From enrollment to the end of the cross over visit at week 2

• Unconditioned Stimulus Expectancy Ratings

  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.

  From enrollment to the end of the cross over visit at week 2

Study Arms (2)

Active taVNS

EXPERIMENTAL

Active transcutaneous auricular vagus nerve stimulation

Device: transcutaneous auricular vagus nerve stimulation

Sham taVNS

SHAM COMPARATOR

Active transcutaneous auricular vagus nerve stimulation

Device: sham transcutaneous auricular vagus nerve stimulation

Interventions

transcutaneous auricular vagus nerve stimulation DEVICE

FDA-cleared Digitimer DS7A Constant Current Stimulator (Digitimer Ltd., USA) will deliver electrical stimulation for 60 mins. Active stimulation will consist of direct electrical stimulation to the inner side of the left tragus (anode on the cymba concha, cathode on the surface of the tragus), thereby stimulating the ABVN. Stimulation parameters will consist of 500μs pulse width, 25Hz frequency, delivered at 200% of each participant's individual perceptual threshold (PT) in 60sec on/off trains.

Active taVNS

sham transcutaneous auricular vagus nerve stimulation DEVICE

FDA-cleared Digitimer DS7A Constant Current Stimulator (Digitimer Ltd., USA) will deliver electrical stimulation for 60 mins. Sham will be delivered to the ear lobe. Stimulation parameters will consist of 500μs pulse width, 25Hz frequency, delivered at 200% of each participant's individual perceptual threshold (PT) in 60sec on/off trains.

Sham taVNS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-80
• Fluent in English
• Experience with a DSM-5 Criterion A trauma (LEC-5)
• Probable PTSD (PCL-5 ≥ 32)

You may not qualify if:

• Visual or Auditory impairment
• Major injury at time of screen or study procedures
• Taking ≥20 mg morphine per day
• Current substance use or intoxication (12-panel drug test)
• Intellectual disability (MoCA)
• Self-inflicted injury
• Occupational injury
• Prisoner
• Ongoing domestic violence
• Pregnant or breastfeeding
• Contraindications for taVNS

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (1)

Tolan Park Research Clinic, Wayne State University

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Combat Disorders; Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Central Study Contacts

Danielle Taylor, PhD

CONTACT

313-774-3606; dtaylo@med.wayne.edu

Study Coordinator

CONTACT

wsu.spark.study@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 1, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): December 1, 2032
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: A. All data will be deposited to the NIMH data archive (NDA) 12 months after the study begins and will be deposited biannually following the first submission. B. Within the first 6 months of an NDA Data Submission agreement will be submitted by the PI through the NDA website, which will allow for access to the NDA Collection page where data will be submitted. The NCT# will be submitted within this agreement. Data will be findable for the research community using the NDA Collection page. An NDA study will be created for each publication and each study will be assigned a digital object identifier (DOI). The DOI will be referenced in the publication so that the research community can access the data used in the publication. C. The research community will have access 1-2 years after study end date. Publication will be linked to a study containing the data used in that publication and may be found using the DOI when the pre-print is available. NDA will determine data preservation duration.
• Access Criteria: NDA will control data access. Researchers will submit a data access request for broad use and must be sponsored by an NIH recognized institution and have a research-related need to access the data. The NDA data access committee will make final determination on which requests to grant.

Locations

US (1)