Transcutaneous Vagal Nerve Stimulation in Veterans With Posttraumatic Stress Disorder (VNS in PTSD)

This study effects the effects of transcutaneous cervical vagal nerve stimulation (tcVNS) or a sham control on brain, physiology, and PTSD symptoms in Veterans with posttraumatic stress disorder (PTSD). Veterans undergo brain imaging and physiological measures in conjunction with traumatic scripts before and after three months of twice daily treatment with tcVNS or sham stimulation at home.

Study Overview

• Status: Recruiting
• Conditions: Stress Disorders, Post-Traumatic
• Intervention / Treatment: Device: Sham; Device: tcVNS

Detailed Description

Description: This study assesses brain function measured with High Resolution Positron Emission Tomography (HR-PET) during exposure to stressful traumatic scripts paired with tcVNS or sham stimulation, with secondary measures of blood inflammatory biomarkers, and sympathetic function. Participants then undergo three months of twice daily home treatment with repeat measures.

Drug/Device Handling: [O-15] radiolabeled water has a half-life of 110 seconds and is made on site at the Emory Center for Systems Imaging (CSI). Dr. Bremner holds the Investigational New Drug (IND) approval for use of radiolabeled water at Emory University. The investigators have performed hundreds of studies in human subjects at Emory and there have been no adverse events or untoward effects to date.

tcVNS with the GammaCore device is approved by the Emory IRB for a recently completed study in PTSD and others in progress for Opioid Use Disorder and was shown to be well tolerated and there have been no adverse events or untoward effects with the device. The FDA granted Breakthrough Device Designation for PTSD for the gammaCore tcVNS device based on the investigators' studies. Devices are blinded by ElectroCore and the devices and information are kept by the Data Manager under double lock and key. Device records are kept by the Data Manager and stored on Redcap or secured research drives. Devices are given to the study team along with a device schedule under direct supervision from the investigator.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Doug J Bremner, MD; Phone Number: (404) 712-9569; Email: James.Bremner@va.gov

Study Locations

• United States
  • Georgia
    • Decatur, Georgia, United States, 30033-4004
      • Recruiting
      • Atlanta VA Medical and Rehab Center, Decatur, GA
      • Contact: Doug J Bremner, MD; Phone Number: (404) 712-9569; Email: James.Bremner@va.gov
      • Principal Investigator: Doug J Bremner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Veterans between the ages of 18 and 75 will be included with a diagnosis of PTSD based on DSM-5 criteria

Exclusion Criteria:

Subjects will be excluded with:

• a history of mild traumatic brain injury (mTBI) based on VA Criteria
• moderate or greater TBI
• positive pregnancy test
• meningitis or other neurological disorder
• alcohol or substance abuse use disorder based on DSM-5 criteria within the past 12 months
• current or lifetime history of schizophrenia, schizoaffective disorder, bipolar I disorder, anorexia nervosa or bulimia, based on DSM-5
• active suicidal ideation with a plan
• a history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness that would preclude participation based on clinical judgment of the PI
• active opiate or benzodiazepine treatment
• history of structural abnormality on brain MRI or CT if one has been performed in the past

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tcVNS; Stimulation twice daily with transcutaneous Vagal Nerve Stimulation (tcVNS)	Device: tcVNS; Active stimulation with transcutaneous Vagal Nerve Stimulation (tcVNS)
Active Comparator: Sham; Stimulation with sham	Device: Sham; Sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PTSD symptoms	Change in PTSD symptoms measured with the Clinician Administered PTSD Scale (CAPS) and PTSD Checklist (PCL) in tcVNS versus sham conditions	Baseline to three months
Brain Activation	Change in brain activation in insula measured with PET in response to trauma scripts with VNS compared to sham	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sympathetic function	Change in pre-ejection period (PEP) during traumatic scripts with VNS compared to sham. PEP is the time from ventricular contraction to aortic valve opening and is a measure of cardiac sympathetic tone	Baseline
Interleukin-6	Change in interleukin 6 concentration in blood in response to traumatic scripts with stimulation with VNS versus stimulation with sham	Baseline

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Doug J Bremner, MD, Atlanta VA Medical and Rehab Center, Decatur, GA

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): July 8, 2027
• Study Completion (Estimated): November 10, 2027

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: PTSD; Stress Disorders, Post-Traumatic; Vagus Nerve
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: MHBP-004-21F; I01CX002331 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De identified data will be made available three months after study completion
• IPD Sharing Time Frame: Three months after study completion
• IPD Sharing Access Criteria: Three months after study completion for twelve months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes