PostTraumatic Stress Disorder
Conditions
Keywords
stress disorders, post-traumatic, posttraumatic stress disorder, PTSD, vagal nerve
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.
Interventions
DEVICEGammaCore/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.
DEVICESham 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.
DRUGO-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.
Sponsors
Georgia Institute of Technology
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vagal Nerve Stimulation Participants randomized to this arm will receive stimulation of the vagus nerve in conjunction with stress exposure.
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 is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V). 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.
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) . Subjects will receive a 20 mCi intravenous bolus of H2\[15O\] for each of the 14 scans during exposure to neutral and traumatic scripts. | 27 |
| Sham Stimulation Participants randomized to this arm will receive sham stimulation of the vagus nerve in conjunction with stress exposure.
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.
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. | 29 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Vagal Nerve Stimulation | Total | Sham Stimulation |
|---|---|---|---|
| Age, Continuous | 31 years STANDARD_DEVIATION 11 | 33 years STANDARD_DEVIATION 12 | 35 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 27 Participants | 14 Participants |
| Region of Enrollment United States | 27 participants | 56 participants | 29 participants |
| Sex: Female, Male Female | 16 Participants | 32 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 24 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 29 |
| other Total, other adverse events | 0 / 27 | 0 / 29 |
| serious Total, serious adverse events | 0 / 27 | 0 / 29 |
Outcome results
Primary
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Interleukin-6 (IL6) | Baseline IL-6 Level | 0.88 pg/ml | Standard Deviation 0.59 |
| Vagal Nerve Stimulation | Level of Interleukin-6 (IL6) | Post Stress Testing IL-6 Level | 1.77 pg/ml | Standard Deviation 1.43 |
| Sham Stimulation | Level of Interleukin-6 (IL6) | Baseline IL-6 Level | 0.84 pg/ml | Standard Deviation 0.61 |
| Sham Stimulation | Level of Interleukin-6 (IL6) | Post Stress Testing IL-6 Level | 2.11 pg/ml | Standard Deviation 2.49 |
Secondary
Level of 3-3 Hydroxykynurenine
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Adrenocorticotropic Hormone
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Anthranilic Acid
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Anthranilic Acid | Baseline Anthranilic Acid Level | 8.32 nM | Standard Deviation 2.68 |
| Vagal Nerve Stimulation | Level of Anthranilic Acid | Post Stress Testing Anthranilic Acid Level | 7.49 nM | Standard Deviation 2.13 |
| Sham Stimulation | Level of Anthranilic Acid | Baseline Anthranilic Acid Level | 7.02 nM | Standard Deviation 1.68 |
| Sham Stimulation | Level of Anthranilic Acid | Post Stress Testing Anthranilic Acid Level | 6.90 nM | Standard Deviation 1.59 |
Secondary
Level of Cortisol
Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Dopamine
Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Epinephrine
Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of High-Mobility Group Protein B1
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of High-Mobility Group Protein B1 | Baseline High-Mobility Group Protein B1 Level | 1,552 ng/mL | — |
| Vagal Nerve Stimulation | Level of High-Mobility Group Protein B1 | Post Stress Testing High-Mobility Group Protein B1 Level | 1,299 ng/mL | Standard Deviation 574 |
| Sham Stimulation | Level of High-Mobility Group Protein B1 | Baseline High-Mobility Group Protein B1 Level | 1,734 ng/mL | Standard Deviation 893 |
| Sham Stimulation | Level of High-Mobility Group Protein B1 | Post Stress Testing High-Mobility Group Protein B1 Level | 1,691 ng/mL | Standard Deviation 942 |
Secondary
Level of Interferon-Gamma
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Interferon-Gamma | Baseline Interferon-Gamma Level | 4.75 pg/mL | Standard Deviation 9.61 |
| Vagal Nerve Stimulation | Level of Interferon-Gamma | Post Stress Testing Interferon-Gamma Level | 4.86 pg/mL | Standard Deviation 10.2 |
| Sham Stimulation | Level of Interferon-Gamma | Baseline Interferon-Gamma Level | 3.43 pg/mL | Standard Deviation 2.58 |
| Sham Stimulation | Level of Interferon-Gamma | Post Stress Testing Interferon-Gamma Level | 8.87 pg/mL | Standard Deviation 27.33 |
Secondary
Level of Interleukin-10 (IL10)
IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Interleukin-12p70 (IL12p70)
IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Interleukin-12p70 (IL12p70) | Baseline Interleukin-12p70 (IL12p70) Level Level | 2.20 pg/ml | Standard Deviation 1.48 |
| Vagal Nerve Stimulation | Level of Interleukin-12p70 (IL12p70) | Post Stress Testing Interleukin-12p70 (IL12p70) Level Level | 1.82 pg/ml | Standard Deviation 0.99 |
| Sham Stimulation | Level of Interleukin-12p70 (IL12p70) | Baseline Interleukin-12p70 (IL12p70) Level Level | 3.22 pg/ml | Standard Deviation 1.68 |
| Sham Stimulation | Level of Interleukin-12p70 (IL12p70) | Post Stress Testing Interleukin-12p70 (IL12p70) Level Level | 2.96 pg/ml | Standard Deviation 2.02 |
Secondary
Level of Interleukin-12p (IL12p)
IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Interleukin-13 (IL13)
IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Interleukin-13 (IL13) | Baseline Interleukin-13 (IL13) Level | 33.77 pg/ml | Standard Deviation 16.87 |
| Vagal Nerve Stimulation | Level of Interleukin-13 (IL13) | Post Stress Testing Interleukin-13 (IL13) Level | 29.17 pg/ml | Standard Deviation 14.03 |
| Sham Stimulation | Level of Interleukin-13 (IL13) | Baseline Interleukin-13 (IL13) Level | 43.10 pg/ml | Standard Deviation 18.78 |
| Sham Stimulation | Level of Interleukin-13 (IL13) | Post Stress Testing Interleukin-13 (IL13) Level | 43.55 pg/ml | Standard Deviation 31.91 |
Secondary
Level of Interleukin-1 Beta
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Interleukin-1 Beta | Baseline Interleukin-1 Beta Level | 0.056 pg/mL | Standard Deviation 0.033 |
| Vagal Nerve Stimulation | Level of Interleukin-1 Beta | Post Stress Testing Interleukin-1 Beta Level | 0.071 pg/mL | Standard Deviation 0.041 |
| Sham Stimulation | Level of Interleukin-1 Beta | Baseline Interleukin-1 Beta Level | 0.086 pg/mL | Standard Deviation 0.056 |
| Sham Stimulation | Level of Interleukin-1 Beta | Post Stress Testing Interleukin-1 Beta Level | 0.085 pg/mL | Standard Deviation 0.077 |
Secondary
Level of Interleukin-2 (IL2)
IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Interleukin-2 (IL2) | Baseline Interleukin-2 (IL2) Level | 0.29 pg/ml | Standard Error 0.22 |
| Vagal Nerve Stimulation | Level of Interleukin-2 (IL2) | Post Stress Testing Interleukin-2 (IL2) Level | 0.36 pg/ml | Standard Error 0.2 |
| Sham Stimulation | Level of Interleukin-2 (IL2) | Baseline Interleukin-2 (IL2) Level | 0.29 pg/ml | Standard Error 0.2 |
| Sham Stimulation | Level of Interleukin-2 (IL2) | Post Stress Testing Interleukin-2 (IL2) Level | 0.27 pg/ml | Standard Error 0.2 |
Secondary
Level of Interleukin-4 (IL4)
IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Interleukin-8 (IL8)
IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Kynurenic Acid
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Kynurenic Acid | Baseline Kynurenic Acid Level | 35.71 pmol/100 microliters | Standard Deviation 9.59 |
| Vagal Nerve Stimulation | Level of Kynurenic Acid | Post Stress Testing Kynurenic Acid Level | 38.81 pmol/100 microliters | Standard Deviation 16.5 |
| Sham Stimulation | Level of Kynurenic Acid | Baseline Kynurenic Acid Level | 43.07 pmol/100 microliters | Standard Deviation 21.13 |
| Sham Stimulation | Level of Kynurenic Acid | Post Stress Testing Kynurenic Acid Level | 37.88 pmol/100 microliters | Standard Deviation 12.37 |
Secondary
Level of Kynurenine
Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Kynurenine | Baseline Kynurenine Level | 4.72 µM | Standard Deviation 5.37 |
| Vagal Nerve Stimulation | Level of Kynurenine | Post Stress Testing Kynurenine Level | 5.04 µM | Standard Deviation 5.81 |
| Sham Stimulation | Level of Kynurenine | Baseline Kynurenine Level | 7.19 µM | Standard Deviation 5.01 |
| Sham Stimulation | Level of Kynurenine | Post Stress Testing Kynurenine Level | 7.06 µM | Standard Deviation 5.64 |
Secondary
Level of Macrophage Migration Inhibitory Factor
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Vagal Nerve Stimulation | Level of Macrophage Migration Inhibitory Factor | Baseline Macrophage Migration Inhibitory Factor Level | 32,204 pg/ml |
| Vagal Nerve Stimulation | Level of Macrophage Migration Inhibitory Factor | Post Stress Testing Macrophage Migration Inhibitory Factor Level | 30,403 pg/ml |
| Sham Stimulation | Level of Macrophage Migration Inhibitory Factor | Baseline Macrophage Migration Inhibitory Factor Level | 31,309 pg/ml |
| Sham Stimulation | Level of Macrophage Migration Inhibitory Factor | Post Stress Testing Macrophage Migration Inhibitory Factor Level | 30,515 pg/ml |
Secondary
Level of Norepinephrine
Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: This outcome was not assessed due to a lack of resources and a focus on other pertinent biomarkers per the literature.
Secondary
Level of Tryptophan
Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Tryptophan | Baseline Tryptophan Level | 50.59 micromole/l | Standard Deviation 11.65 |
| Vagal Nerve Stimulation | Level of Tryptophan | Post Stress Testing Tryptophan Level | 54.42 micromole/l | Standard Deviation 13.21 |
| Sham Stimulation | Level of Tryptophan | Baseline Tryptophan Level | 55.80 micromole/l | Standard Deviation 15.74 |
| Sham Stimulation | Level of Tryptophan | Post Stress Testing Tryptophan Level | 57.79 micromole/l | Standard Deviation 14.38 |
Secondary
Level of Tumor Necrosis Factor (TNF)-Alpha
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.
Time frame: Baseline, Post Stress Testing (Up to 4 Hours)
Population: Due to technical reasons and/or limited blood draw, the number of participants analyzed is less than the number of participants that completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Level of Tumor Necrosis Factor (TNF)-Alpha | Baseline Tumor Necrosis Factor (TNF)-alpha Level | 2.81 pg/mL | Standard Deviation 1.28 |
| Vagal Nerve Stimulation | Level of Tumor Necrosis Factor (TNF)-Alpha | Post Stress Testing Tumor Necrosis Factor (TNF)-alpha Level | 2.63 pg/mL | Standard Deviation 1.03 |
| Sham Stimulation | Level of Tumor Necrosis Factor (TNF)-Alpha | Baseline Tumor Necrosis Factor (TNF)-alpha Level | 2.37 pg/mL | Standard Deviation 0.87 |
| Sham Stimulation | Level of Tumor Necrosis Factor (TNF)-Alpha | Post Stress Testing Tumor Necrosis Factor (TNF)-alpha Level | 2.26 pg/mL | Standard Deviation 0.74 |