Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder
Condition: PostTraumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): GammaCore/electroCore non-invasive VNS device; Sham gammaCore/electroCore; O-15 water
Intervention type(s): Device; Device; Drug
Intervention description(s): Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus (the current amplitude) is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V), the burst frequency to 5 kilohertz (kHz), and the envelope frequency to 25 Hz. These are the standard frequency settings that electroCore has demonstrated to be most effective in capturing the vagus nerve based on evoked potential studies. The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.; Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.; Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Other
Keywords: stress disorders, post-traumatic; posttraumatic stress disorder; PTSD; vagal nerve