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NCT Number: NCT04437498

Vagal Nerve Stimulation in mTBI

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are important conditions for the Veterans Administration (VA) that frequently occur together in combat Veterans from the conflicts in Afghanistan and Iraq. In many Veterans these become chronic, raising the risk the burden of neurotrauma can worsen over time. This study will examine a new intervention called non-invasive Vagal Nerve Stimulation (nVNS) and its effects on memory and symptoms of PTSD and mTBI as well as brain and physiology in Veterans with mTBI and PTSD.

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Key information

Conditions

PTSD Brain Diseases Brain Injuries Brain Injuries, Traumatic Central Nervous System Diseases Craniocerebral Trauma Mental Disorders Nervous System Diseases Stress Disorders, Post-Traumatic Stress Disorders, Traumatic Trauma and Stressor Related Disorders Trauma, Nervous System Wounds and Injuries mTBI

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

Location status: Recruiting

Location contact

Doug J Bremner, MD

CONTACT

[email protected]

(404) 712-9569

Doug J Bremner, MD

PRINCIPAL_INVESTIGATOR

About this study

This projects will assess the effects of non-invasive Vagal Nerve Stimulation (nVNS) on neurobiology and cognition in combat Veterans with mild Traumatic Brain Injury (mTBI) and co-morbid posttraumatic stress disorder (PTSD) during the performance of stressful tasks (traumatic scripts, mental arithmetic) and verbal declarative memory tasks using measurement of memory performance, peripheral inflammatory markers in blood (IL6) and cardiovascular responses using wearable gated sensing devices and electro- and seismocardiography, as well as brain response (anterior cingulate, hippocampus) measured with High Resolution Positron Emission Tomography (HR-PET) and radiolabelled water (15O[H2O]). The investigators hypothesize that nVNS but not sham control will result in enhanced memory, and hippocampal activation with memory encoding, and reduced cardiovascular, sympathetic, and inflammatory responses to stress. The investigators will also assess the effects of nVNS and sham on memory retention when applied to the encoding phase of a declarative memory learning task repeated daily over a four day period and on ratings of PTSD and pain in Veterans with mTBI and co-morbid PTSD and repeat assessments after three months of twice daily treatments.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Veterans with mTBI and PTSD

Exclusion criteria

  • amnesia for the inciting event lasted longer than 24 hours
  • Glasgow Coma Scale Score after 30 minutes was less than 13
  • loss of consciousness more than 30 minutes
  • positive pregnancy test
  • meningitis or other neurological disorder other than mTBI
  • alcohol or substance abuse use disorder based on the SCID within the past 12 months
  • current or lifetime history of schizophrenia, schizoaffective disorder, bipolar disorder, anorexia nervosa or bulimia, based on the SCID
  • active suicidal ideation based on criteria outlined below
  • a history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness
  • active neuroleptic, opiate, or benzodiazepine treatment
  • structural abnormality on brain MRI or CT

Treatment and study plan

Sham stimulation

Device

non invasive vagal nerve stimulation

nVNS

Device

active vns stimulation

Primary outcomes

  1. CAPS

    Time frame: three months

    The Clinician Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) is a measure of PTSD symptoms with a range of 0-80 and higher score indicating more severe PTSD symptoms. The investigators will compare change from baseline to post treatment with active vagal nerve stimulation (VNS) or sham stimulation twice daily.

  2. insula

    Time frame: 10 minutes

    Blood flow in the insula is measured with positron emission tomography (PET) and radiolabelled water during the performance of stress tasks. The investigators will compare blood flow in the insula to whole brain blood flow ratio during stress tasks (listening to personalized traumatic scripts) versus control tasks in the VNS versus sham groups with hypothesis of blocked insula blood flow with VNS

  3. HVLT-R % retention

    Time frame: baseline versus three months

    The Hopkins Verbal Learning Test-Revised (HVLT-R) is a test of declarative memory learning that involves the learning of 12 nouns, four from each of three semantic categories, learned over three learning trials, followed 20 minutes later by a delayed free recall trial and recognition trial composed of 24 words with 12 false positives. The percent (%) retention is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3. HLVT-R % retention has a range of 0-100 with 100 being best and 0 worst performance. Baseline and three months post treatment paired with sham or active stimulation are compared.

  4. Change in IL6 Concentration in Blood with Stress

    Time frame: Baseline to 120 minutes after stress

    Interleukin-6 (IL6) response to stress paired with active or sham stimulation. IL6 is an inflammatory biomarker measured in blood. The investigators will compare IL6 response to stress in VNS versus sham treated groups.

  5. hippocampal activation

    Time frame: 10 minutes

    Blood flow in the hippocampus is measured with positron emission tomography (PET) and radiolabelled water during the performance of declarative memory tasks. The investigators will compare blood flow in the hippocampus to whole brain blood flow ratio during memory tasks versus control tasks in the VNS versus sham groups with hypothesis of increased hippocampal blood flow with VNS

Secondary outcomes

  1. PPG amplitude

    Time frame: Change from baseline to 5 seconds after the termination of stimulation paired with stress

    Photoplethysmography (PPG) amplitude is a measure of peripheral vasoconstriction which is a marker of sympathetic response to stress with active or sham. PPG amplitude is the diameter of the blood vessel in the finger, the investigators will measure change from baseline to post active vagal nerve stimulation versus sham stimulation with stress.

Study contacts

Contact information is provided by the study sponsor or research team.

Anna Woodbury, MD

CONTACT

[email protected]

(404) 321-6111 ext. 6939

Doug J Bremner, MD

CONTACT

[email protected]

(404) 712-9569

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Collaborators

  • Atlanta VA Medical Center

Registry information

Official study title

Non-Invasive Vagal Nerve Stimulation in Veterans With Mild Traumatic Brain Injury (mTBI)

Acronym: VNS mTBI

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Jun 18, 2020
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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