Vagal Nerve Stimulation in mTBI

PTSD Clinical Trial

— VNS mTBI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04437498
• Other study ID #: N3418-I
• Secondary ID: I01RX003418
• Status: Recruiting
• Phase: N/A
• Start date: February 25, 2021
• Est. completion date: January 15, 2026

Study information

• Verified date: April 2024
• Source: VA Office of Research and Development
• Contact: Doug J Bremner, MD
• Phone: (404) 712-9569
• Email: James.Bremner[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 15, 2026
• Est. primary completion date: September 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• mTBI
• PTSD

Intervention

Device:
• sham stimulation
non invasive vagal nerve stimulation
• nVNS
active vns stimulation

Locations

Country	Name	City	State
United States	Atlanta VA Medical and Rehab Center, Decatur, GA	Decatur	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	Atlanta VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. We will compare change from baseline to post treatment with active vagal nerve stimulation (VNS) or sham stimulation twice daily.	three months
Primary	insula	Blood flow in the insula is measured with positron emission tomography (PET) and radiolabelled water during the performance of stress tasks. We 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	10 minutes
Primary	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.	baseline versus three months
Primary	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. We compare IL6 response to stress in VNS versus sham treated groups.	Baseline to 120 minutes after stress
Primary	hippocampal activation	Blood flow in the hippocampus is measured with positron emission tomography (PET) and radiolabelled water during the performance of declarative memory tasks. We 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	10 minutes
Secondary	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, we measure change from baseline to post active vagal nerve stimulation versus sham stimulation with stress.	Change from baseline to 5 seconds after the termination of stimulation paired with stress