Vagal Nerve Stimulation in mTBI

NCT04437498 | Recruiting FDA Device

• 2 other identifiers: N3418-II01RX003418
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

PTSD; mTBI

Keywords

vagus nerve; stress disorders, posttraumatic; traumatic brain injury; memory; hippocampus; emission tomography

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (1)

• PPG amplitude

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

Study Arms (2)

nVNS

EXPERIMENTAL

non invasive vagal nerve stimulation

Device: nVNS

sham

SHAM COMPARATOR

sham stimulation

Device: sham stimulation

Interventions

sham stimulation DEVICE

non invasive vagal nerve stimulation

sham

nVNS DEVICE

active vns stimulation

nVNS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Veterans with mTBI and PTSD

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Atlanta VA Medical Center: collaborator

Study Sites (1)

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Doug J Bremner, MD

  Atlanta VA Medical and Rehab Center, Decatur, GA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Doug J Bremner, MD

CONTACT

(404) 712-9569; James.Bremner@va.gov

Anna Woodbury, MD

CONTACT

(404) 321-6111; Anna.Woodbury@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: code for active and sham devices kept by non study personnel.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Veterans are randomized to double blind treatment with active non-invasive Vagal Nerve Stimulation (nVNS) or a sham control.

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 18, 2020
• Study Start: February 25, 2021
• Primary Completion (Estimated): May 21, 2026
• Study Completion (Estimated): July 9, 2026
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: three months after study end
• Access Criteria: de identified data for three years

Locations

US (1)