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Vagal Nerve Stimulation in mTBI (VNS mTBI)

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ClinicalTrials.gov Identifier: NCT04437498
Recruitment Status : Recruiting
First Posted : June 18, 2020
Last Update Posted : March 14, 2022
Sponsor:
Collaborator:
Atlanta VA Medical Center
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE May 29, 2020
First Posted Date  ICMJE June 18, 2020
Last Update Posted Date March 14, 2022
Actual Study Start Date  ICMJE February 25, 2021
Estimated Primary Completion Date September 20, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • 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.
  • 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
  • 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. We 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. 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vagal Nerve Stimulation in mTBI
Official Title  ICMJE Non-Invasive Vagal Nerve Stimulation in Veterans With Mild Traumatic Brain Injury (mTBI)
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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
Condition  ICMJE
  • PTSD
  • mTBI
Intervention  ICMJE
  • Device: sham stimulation
    non invasive vagal nerve stimulation
  • Device: nVNS
    active vns stimulation
Study Arms  ICMJE
  • Experimental: nVNS
    non invasive vagal nerve stimulation
    Intervention: Device: nVNS
  • Sham Comparator: sham
    sham stimulation
    Intervention: Device: sham stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 17, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 15, 2025
Estimated Primary Completion Date September 20, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Doug Bremner, MD (404) 712-9569 James.Bremner@va.gov
Contact: Anna Woodbury, MD (404) 321-6111 ext 6939 Anna.Woodbury@va.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04437498
Other Study ID Numbers  ICMJE N3418-I
I01RX003418 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: three months after study end
Access Criteria: de identified data for three years
Current Responsible Party VA Office of Research and Development
Original Responsible Party Same as current
Current Study Sponsor  ICMJE VA Office of Research and Development
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Atlanta VA Medical Center
Investigators  ICMJE
Principal Investigator: Doug Bremner, MD Atlanta VA Medical and Rehab Center, Decatur, GA
PRS Account VA Office of Research and Development
Verification Date February 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP