Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder

May 20, 2021 updated by: J. Douglas Bremner, MD, Emory University

Closed Loop Vagal Nerve Stimulation in Patients With Posttraumatic Stress Disorder

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Vagal Nerve Stimulation
Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.
Device: GammaCore/electroCore non-invasive VNS 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.
Drug: O-15 water
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_COMPARATOR: Sham Stimulation
Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.
Drug: O-15 water
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.
Device: Sham gammaCore/electroCore
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Level of Interleukin-6 (IL6)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Level of Tryptophan
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Kynurenine
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Kynurenic Acid
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Kynurenic acid level will be collected via blood draw. Change is defined as the difference in kynurenic acid level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of 3-3 Hydroxykynurenine
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
3-3 hydroxykynurenine level will be collected via blood draw. Change is defined as the difference in 3-3 hydroxykynurenine level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Anthranilic Acid
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Anthranilic Acid level will be collected via blood draw. Change is defined as the difference in anthranilic acid level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Tumor Necrosis Factor (TNF)-Alpha
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
TNF-alpha level will be collected via blood draw. Change is defined as the difference in TNF-alpha level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interferon-Gamma
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Interferon-Gamma level will be collected via blood draw. Change is defined as the difference in Interferon-Gamma level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-1 Beta
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Interleukin-1 Beta level will be collected via blood draw. Change is defined as the difference in Interleukin-1 Beta level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-2 (IL2)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-4 (IL4)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-8 (IL8)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-10 (IL10)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-12p70 (IL12p70)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-12p (IL12p)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Interleukin-13 (IL13)
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Macrophage Migration Inhibitory Factor
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Macrophage migration inhibitory factor will be collected via blood draw. Change is defined as the difference in factor level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of High-Mobility Group Protein B1
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
High-mobility group protein B1 level will be collected via blood draw. Change is defined as the difference in high-mobility group protein B1 level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Adrenocorticotropic Hormone
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Adrenocorticotropic hormone level will be collected via blood draw. Change is defined as the difference in adrenocorticotropic hormone level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Cortisol
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Epinephrine
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Dopamine
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)
Level of Norepinephrine
Time Frame: Baseline, Post Stress Testing (Up to 4 Hours)
Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.
Baseline, Post Stress Testing (Up to 4 Hours)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Emory University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Georgia Institute of Technology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 19, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 21, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 21, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 12, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 14, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 14, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00091171

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings