Clinical trial NCT02992899: Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder
Official title: Closed Loop Vagal Nerve Stimulation in Patients With Posttraumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: PostTraumatic Stress Disorder
Keywords: stress disorders, post-traumatic
posttraumatic stress disorder
PTSD
vagal nerve
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Georgia Institute of Technology
First posted: 2016-12-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The tasks of the project are to map the potency and kinetics of the neurologic, autonomic peripheral, inflammatory, and behavioral responses to vagal nerve stimulation (VNS) vs. sham treatment, at baseline and in response to stressful traumatic scripts related to personal traumatic events, as well as a series of other stressors.

Detailed description: The purpose of this project is to develop the fundamental physiological understanding of feedback controlled vagal nerve stimulation (VNS) using positron emission tomography (PET) brain imaging and blood biomarker measurement with stress in healthy individuals and individuals with PTSD. Healthy human subjects with a history of psychological trauma but without the diagnosis of a psychiatric disorder (Phase 1), and human subjects with a history of PTSD (Phase 2), undergo PET imaging of the brain in conjunction with VNS or a sham treatment during exposure to neutral scripts and scripts of personal traumatic events. Blood is drawn simultaneously for measurement of a variety of stress responsive biomarkers, including inflammatory markers and neurohormones. A second PET scan with biomarkers assesses the delayed effects of VNS. On two other days subjects undergo exposure to random stressors with VNS or sham in conjunction with measurement of stress biomarkers.

Eligibility criteria: Inclusion Criteria:

Phase 1:

* Do not meet criteria for post traumatic stress disorder (PTSD) or other major mental disorder as determined by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 SCID) interview for PTSD
* Have a history of psychological trauma as defined by DSM-5.

Phase 2:

- Meet criteria for PTSD as determined by the Structured Clinical Interview for DSM-5 (SCID) interview for PTSD.

Exclusion Criteria:

* Positive pregnancy test
* Meningitis
* Traumatic brain injury
* Neurological disorder or organic mental disorder
* History of loss of consciousness greater than one minute
* Alcohol abuse or substance abuse or dependence based on the SCID within the past 12 months
* Positive toxicology screen
* Current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia, based on the SCID
* A history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness
* Evidence of a major medical or neurological illness on physical examination or as a result of laboratory studies (complete blood count (CBC), blood urea nitrogen (BUN), creatinine, blood sugar, electrolytes, liver and thyroid function tests, urinalysis, and EKG)
* Active implantable device (i.e. pacemaker)
* Carotid atherosclerosis
* Cervical vagotomy

Primary outcomes:
measure: Level of Interleukin-6 (IL6)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
Secondary outcomes:
measure: Level of Tryptophan
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Kynurenine
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Kynurenic Acid
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of 3-3 Hydroxykynurenine
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Anthranilic Acid
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Tumor Necrosis Factor (TNF)-Alpha
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interferon-Gamma
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-1 Beta
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-2 (IL2)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-4 (IL4)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-8 (IL8)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-10 (IL10)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-12p70 (IL12p70)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-12p (IL12p)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Interleukin-13 (IL13)
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Macrophage Migration Inhibitory Factor
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of High-Mobility Group Protein B1
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Adrenocorticotropic Hormone
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Cortisol
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Epinephrine
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Dopamine
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
measure: Level of Norepinephrine
timeFrame: Baseline, Post Stress Testing (Up to 4 Hours)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: James D Bremner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wittbrodt MT, Gurel NZ, Nye JA, Shandhi MMH, Gazi AH, Shah AJ, Pearce BD, Murrah N, Ko YA, Shallenberger LH, Vaccarino V, Inan OT, Bremner JD. Noninvasive Cervical Vagal Nerve Stimulation Alters Brain Activity During Traumatic Stress in Individuals With Posttraumatic Stress Disorder. Psychosom Med. 2021 Nov-Dec 01;83(9):969-977. doi: 10.1097/PSY.0000000000000987.
citation: Gurel NZ, Wittbrodt MT, Jung H, Shandhi MMH, Driggers EG, Ladd SL, Huang M, Ko YA, Shallenberger L, Beckwith J, Nye JA, Pearce BD, Vaccarino V, Shah AJ, Inan OT, Bremner JD. Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial. Neurobiol Stress. 2020 Oct 20;13:100264. doi: 10.1016/j.ynstr.2020.100264. eCollection 2020 Nov.
citation: Gazi AH, Gurel NZ, Richardson KLS, Wittbrodt MT, Shah AJ, Vaccarino V, Bremner JD, Inan OT. Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation. JMIR Mhealth Uhealth. 2020 Sep 22;8(9):e20488. doi: 10.2196/20488.