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Vagal Nerve Stimulation in mTBI (VNS mTBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04437498
Recruitment Status : Not yet recruiting
First Posted : June 18, 2020
Last Update Posted : June 18, 2020
Sponsor:
Collaborator:
Atlanta VA Medical Center
Information provided by (Responsible Party):
VA Office of Research and Development

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.

Condition or disease Intervention/treatment Phase
PTSD mTBI Device: sham stimulation Device: nVNS Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Veterans are randomized to double blind treatment with active non-invasive Vagal Nerve Stimulation (nVNS) or a sham control.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: code for active and sham devices kept by non study personnel.
Primary Purpose: Treatment
Official Title: Non-Invasive Vagal Nerve Stimulation in Veterans With Mild Traumatic Brain Injury (mTBI)
Estimated Study Start Date : August 1, 2020
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : June 28, 2024

Arm Intervention/treatment
Experimental: nVNS
non invasive vagal nerve stimulation
Device: nVNS
active vns stimulation

Sham Comparator: sham
sham stimulation
Device: sham stimulation
non invasive vagal nerve stimulation




Primary Outcome Measures :
  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. We 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. 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

  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. We 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. 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


Secondary Outcome Measures :
  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, we measure change from baseline to post active vagal nerve stimulation versus sham stimulation with stress.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04437498


Contacts
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Contact: Doug Bremner, MD (404) 712-9569 James.Bremner@va.gov
Contact: Anna Woodbury, MD (404) 321-6111 ext 6939 Anna.Woodbury@va.gov

Locations
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United States, Georgia
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, United States, 30033
Contact: Antonio J Laracuente, MBA    404-321-6111 ext 7740    Antonio.Laracuente03@va.gov   
Contact: Michael Hart, MD    (404) 321-6111 ext 6170    Michael.Hart3@va.gov   
Principal Investigator: Doug Bremner, MD         
Sponsors and Collaborators
VA Office of Research and Development
Atlanta VA Medical Center
Investigators
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Principal Investigator: Doug Bremner, MD Atlanta VA Medical and Rehab Center, Decatur, GA
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT04437498    
Other Study ID Numbers: N3418-I
I01 RX003418 ( Other Grant/Funding Number: VA Merit RR&D )
First Posted: June 18, 2020    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: three months after study end
Access Criteria: de identified data for three years

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by VA Office of Research and Development:
vagus nerve
stress disorders, posttraumatic
traumatic brain injury
memory
hippocampus
emission tomography
Additional relevant MeSH terms:
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Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries