Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder

NCT02992899 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 1 other identifier: IRB00091171
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

PostTraumatic Stress Disorder

Keywords

stress disorders, post-traumatic; posttraumatic stress disorder; PTSD; vagal nerve

Outcome Measures

Primary Outcomes (1)

• Level of Interleukin-6 (IL6)

  IL6 level will be collected via blood draw. Change is defined as the difference in IL6 level from baseline to post emotional stress testing.

  Baseline, Post Stress Testing (Up to 4 Hours)

Secondary Outcomes (22)

• Level of Tryptophan

  Baseline, Post Stress Testing (Up to 4 Hours)

• Level of Kynurenine

  Baseline, Post Stress Testing (Up to 4 Hours)

• Level of Kynurenic Acid

  Baseline, Post Stress Testing (Up to 4 Hours)

• Level of 3-3 Hydroxykynurenine

  Baseline, Post Stress Testing (Up to 4 Hours)

• Level of Anthranilic Acid

  Baseline, Post Stress Testing (Up to 4 Hours)

Study Arms (2)

Vagal Nerve Stimulation

EXPERIMENTAL

Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.

Device: GammaCore/electroCore non-invasive VNS device; Drug: O-15 water

Sham Stimulation

SHAM COMPARATOR

Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.

Device: Sham gammaCore/electroCore; Drug: O-15 water

Interventions

GammaCore/electroCore non-invasive VNS device DEVICE

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.

Vagal Nerve Stimulation

Sham gammaCore/electroCore DEVICE

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.

Sham Stimulation

O-15 water DRUG

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.

Sham Stimulation; Vagal Nerve Stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Georgia Institute of Technology: collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (3)

• 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.

  PMID: 34292205 DERIVED

• 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.

  PMID: 33344717 DERIVED

• 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.

  PMID: 32960179 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Douglas Bremner
• Organization: Emory University

doug.bremner@emory.edu

404-712-9569

Study Officials

• James D Bremner, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 14, 2016
• Study Start: April 19, 2017
• Primary Completion: September 21, 2019
• Study Completion: September 21, 2019
• Last Updated: June 14, 2021
• Results First Posted: May 19, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)