Clinical trial NCT04437498: Vagal Nerve Stimulation in mTBI
Official title: Non-Invasive Vagal Nerve Stimulation in Veterans With Mild Traumatic Brain Injury (mTBI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: PTSD
mTBI
Keywords: vagus nerve
stress disorders, posttraumatic
traumatic brain injury
memory
hippocampus
emission tomography
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Atlanta VA Medical Center
First posted: 2020-06-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Veterans are randomized to double blind treatment with active non-invasive Vagal Nerve Stimulation (nVNS) or a sham control.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: CAPS
timeFrame: three months
measure: insula
timeFrame: 10 minutes
measure: HVLT-R % retention
timeFrame: baseline versus three months
measure: Change in IL6 Concentration in Blood with Stress
timeFrame: Baseline to 120 minutes after stress
measure: hippocampal activation
timeFrame: 10 minutes
Secondary outcomes:
measure: PPG amplitude
timeFrame: Change from baseline to 5 seconds after the termination of stimulation paired with stress
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
Study officials:
affiliation: Atlanta VA Medical and Rehab Center, Decatur, GA
name: Doug J Bremner, MD
role: PRINCIPAL_INVESTIGATOR
References: