PTSDVNS mTBINCT04437498
Vagal Nerve Stimulation in mTBI
A study testing nVNS in people with PTSD and mTBI, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- What is being tested?
- nVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2021to 1 Jul 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Veterans with Mild Traumatic Brain Injury (mTBI) and post-Traumatic Stress Disorder (PTSD)
Who cannot join
- 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 Mild Traumatic Brain Injury (mTBI)
- alcohol or substance abuse use disorder based on the SCID within the past 12 months
Show all 11Show fewer
- 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 magnetic resonance imaging (MRI) or computed tomography (CT)
Trial locations and contacts
1 site in 1 country.
United States1 site
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033-4004
About this study
Official title: Non-Invasive Vagal Nerve Stimulation in Veterans With Mild Traumatic Brain Injury (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.
Read the detailed description
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.
- Being tested
- sham stimulation, nVNS
- Keywords
- vagus nerve, stress disorders, posttraumatic, traumatic brain injury, memory, hippocampus, emission tomography
- Medical subject headings
- Stress Disorders, Post-Traumatic, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sham stimulationDevice
non invasive vagal nerve stimulation
nVNSDevice
active vns stimulation
| Study group | Role | What they receive |
|---|---|---|
| nVNS | Experimental | non invasive vagal nerve stimulation Receives: Device: nVNS |
| sham | Sham comparator | sham stimulation Receives: Device: sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
CAPS
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.
Measured: three months
Insula
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
Measured: 10 minutes
HVLT-R % retention
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.
Measured: baseline versus three months
Change in IL6 Concentration in Blood with 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.
Measured: Baseline to 120 minutes after stress
Hippocampal activation
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
Measured: 10 minutes
Secondary outcomes (1)
PPG amplitude
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.
Measured: Change from baseline to 5 seconds after the termination of stimulation paired with stress
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start25 Feb 2021
- Primary completion1 Jul 2026
- Study completion1 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Veterans are randomized to double blind treatment with active non-invasive Vagal Nerve Stimulation (nVNS) or a sham control.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Atlanta VA Medical Center
- Responsible party
- Sponsor
- Investigators
- Doug J Bremner, MD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04437498
- Sponsor's protocol ID
- N3418-I
- Other IDs
- I01RX003418
- Acronym
- VNS mTBI
- Status last verified
- Oct 2026
- First submitted
- 29 May 2020
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Invasive Vagal Nerve Stimulation in Veterans With Mild Traumatic Brain Injury (mTBI)
- ClinicalTrials.gov ID
- NCT04437498
- Acronym / sponsor ID
- VNS mTBI / N3418-I
- Keywords
- vagus nerve, stress disorders, posttraumatic, traumatic brain injury, memory, hippocampus, emission tomography
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Atlanta VA Medical Center
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 1 Jul 2026 (actual)
- Study completion
- 1 Jul 2026 (actual)
- First posted
- 18 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Veterans are randomized to double blind treatment with active non-invasive Vagal Nerve Stimulation (nVNS) or a sham control.
| Arm | Type | Receives |
|---|---|---|
| nVNS | Experimental | Device: nVNSnon invasive vagal nerve stimulation |
| sham | Sham comparator | Device: sham stimulationsham stimulation |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Veterans with Mild Traumatic Brain Injury (mTBI) and post-Traumatic Stress Disorder (PTSD)
Key exclusion criteria (11 listed)
- 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 Mild Traumatic Brain Injury (mTBI)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sham stimulationnon invasive vagal nerve stimulation | Device | sham |
| nVNSactive vns stimulation | Device | nVNS |
Primary outcome
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.
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
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.
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.
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
1 secondary outcome
PPG amplitude
Time frame: Change from baseline to 5 seconds after the termination of stimulation paired with stress
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: Yes
Related trials for PTSD
RecruitingPhase 1
Rehabilitation Through Virtual Immersion & Integrated Exposure for Mild Traumatic Brain Injury (ReVIVE for mTBI)
Traumatic Brain Injuries, TBI (Traumatic Brain Injury)
Recruiting
Randomized Trial of Tele Vs. Clinic TF-CBT in Puerto Rico
Post-Traumatic Stress Disorder
RecruitingPhase 3
Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression
Major Depression
RecruitingPhase 2/3
Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder
PTSD - Post Traumatic Stress Disorder, PTSD
Not yet recruiting
Enhancing Operational Readiness With Digital Self-Managed Cognitive Behavioral Therapy for Insomnia (CBTI)
Insomnia, Depression - Major Depressive Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Doug J Bremner, MD principal investigator
Atlanta VA Medical and Rehab Center, Decatur, GA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing nVNS in people with PTSD and mTBI, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CAPS (time frame: three months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.