Transcutaneous Vagal Nerve Stimulation in Veterans With Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Transcutaneous Vagal Nerve Stimulation in Veterans With Posttraumatic Stress Disorder

Conditions
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Stress Disorders, Post-Traumatic

Intervention / Treatment
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* Device: tcVNS
* Device: sham


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: tcVNS versus sham stimulation
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tcVNS<br>Stimulation twice daily with transcutaneous Vagal Nerve Stimulation (tcVNS) | Device: tcVNS<br>* active stimulation with transcutaneous Vagal Nerve Stimulation (tcVNS)<br>|
| Active Comparator: sham<br>stimulation with sham | Device: sham<br>* sham stimulation<br>|

What is the study measuring?
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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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stress Disorders, Post-Traumatic, PTSD, Vagus Nerve