Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder

Phase 3

Completed

• Conditions: PostTraumatic Stress Disorder
• Interventions: Device: GammaCore/electroCore non-invasive VNS device; Device: Sham gammaCore/electroCore; Drug: O-15 water

• Registration Number: NCT02992899
• Lead Sponsor: Emory University

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.

Study Timeline

• Study First Submitted: 2016-12-12
• Study First Submitted QC: 2016-12-12
• Study First Posted: 2016-12-14
• Study Start: 2017-04-19
• Primary Completion: 2019-09-21
• Study Completion: 2019-09-21
• Disposition First Submitted: 2020-08-28
• Disposition First Submitted QC: 2020-08-28
• Disposition First Posted: 2020-09-02
• Results First Submitted: 2021-04-26
• Results First Submitted QC: 2021-04-26
• Status Verified: 2021-05
• Results First Posted: 2021-05-19
• Last Update Submitted: 2021-05-20
• Last Update Posted: 2021-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vagal Nerve Stimulation	GammaCore/electroCore non-invasive VNS device	Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.
Sham Stimulation	Sham gammaCore/electroCore	Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.
Vagal Nerve Stimulation	O-15 water	Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.
Sham Stimulation	O-15 water	Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.

Primary Outcome Measures

Name	Time	Method
Level of Interleukin-6 (IL6)	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.

Secondary Outcome Measures

Name	Time	Method
Level of Tryptophan	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.
Level of Kynurenine	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.
Level of Kynurenic Acid	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.
Level of 3-3 Hydroxykynurenine	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.
Level of Anthranilic Acid	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.
Level of Tumor Necrosis Factor (TNF)-Alpha	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.
Level of Interferon-Gamma	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.
Level of Interleukin-1 Beta	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.
Level of Interleukin-2 (IL2)	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.
Level of Interleukin-4 (IL4)	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.
Level of Interleukin-8 (IL8)	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.
Level of Interleukin-10 (IL10)	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.
Level of Interleukin-12p70 (IL12p70)	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.
Level of Interleukin-12p (IL12p)	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.
Level of Interleukin-13 (IL13)	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.
Level of Macrophage Migration Inhibitory Factor	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.
Level of High-Mobility Group Protein B1	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.
Level of Adrenocorticotropic Hormone	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.
Level of Cortisol	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.
Level of Epinephrine	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.
Level of Dopamine	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.
Level of Norepinephrine	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.

Trial Locations

Locations (1)

Emory University; 🇺🇸 Atlanta, Georgia, United States