taVNS to Reduce PTSD Symptoms in WTC Responders

Study Overview
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Brief Summary
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This study seeks to conduct a randomized, double-blind pilot study, to determine whether the Transcutaneous Auricular Vagus Nerve Stimulation and study procedure are feasible and acceptable for use with World Trade Center responders with Post Traumatic Stress Disorder.

Detailed Description
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Participants will be randomized to one of two groups; one that receives stimulation and one that does not. Once their device is ready (roughly 1 month), they will be asked to participate in a baseline questionnaire. They will also be given a phone to interface with the device and record their usage and will use the device for one 15-minute session under the supervision of members of the research team and be monitored using a combination of non-invasive equipment, including an brain activity monitoring cap, blood pressure cuff (to monitor blood pressure), a respiratory belt (to monitor respirations) and an eye tracking device (to monitor eye movement). Researchers are using these tests to see if there are any inflammatory, neural, and cardiovascular changes that relate to the treatment. A research nurse will collect 12 mL of blood (roughly 2 tsp) before and after their session. Blood will be drawn to look at markers of inflammation before using the device, after using the device, and again at the 6-week follow-up visit. They will then be asked to complete a survey regarding the stimulation device on an iPad. After their initial visit, they will be instructed to use the device twice a day, every day at home, for 15 minutes over 8 weeks. After 8 weeks, they will be asked to come in for a final visit, where they will be asked to complete another 15-minute device session, blood draw and survey regarding their experiences.

Official Title
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Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) to Reduce Post Traumatic Stress Disorder (PTSD) Symptoms in World Trade Center (WTC) Responders

Conditions
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Stress Disorders, Post-Traumatic

Intervention / Treatment
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* Device: taVNS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: being a Queens WTCHP responder who agreed to be contacted to participate in research having PTSD as per DSM criteria indicated by the GRDC having elevated PTSD symptoms, indicated by a PCL-S93 score > 44 during an annual monitoring visit between 2018-2020 having a score of 33 or greater on the PCL-594 delivered during the initial phone screen to determine current symptomatology meeting diagnostic indication of PTSD using a Clinician-Administered PTSD Scale (CAPS), which is a clinical interview assessment.95 Exclusion criteria: being physically/mentally unable to consent and participate inability to speak, read, or write in English, exhibiting any current psychotic or manic symptoms, active substance dependence, or current suicidal or homicidal intent/plan, as per the standard MINI neuropsychological assessment.96 active disease involving the auricle or ear canal (e.g., otitis media, tinnitus, infection, perforated tympanic membrane, vestibular and/or balance, excessive cerumen production, skin irritation), unwilling to remove a piercing (e.g., daith or tragus), or use a device (e.g., hearing aid, cochlear implant) that would preclude daily use of the earpiece. history of unilateral or bilateral vagotomy. Current pregnancy (self-report) previously implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators, VNS). other major conditions, that in the judgment of the investigators/WTCHP medical staff, would make the participant unsuitable for inclusion or would interfere with the participant participating in or completing the study. these include: current treatment with psychotropic medication, including tricyclics, antipsychotics, mood stabilizers, bupropion, barbiturates, stimulants, antiepileptics, opioid medications. current diagnosis or history of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, neurologic, gastrointestinal, or immunologic. history of any of the following cardiovascular conditions: Moderate to severe congestive heart failure (New York Heart Association class III or IV); Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting; Uncontrolled hypertension as defined by a confirmed systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg. history of or active seizure disorder. history of recurrent vasovagal syncope episodes. diagnosis of cancer (other than non-invasive skin cancer or carcinoma in-situ of the cervix) within the 5 years prior to study entry. history of concurrent illness that requires hospitalization within 30 days prior to study entry have hypertension/hypotension uncontrolled by medication participation in another investigational trial during the 30 days prior to study entry or during this project

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study seeks to conduct a randomized, double-blind placebo-controlled parallel-design pilot study, to determine whether the taVNS intervention and study methodology are feasible and acceptable for use with WTC responders with PTSD. It is important that the design is double-blind and placebo-controlled in order to have the most appropriate control and to limit bias on the part of the participant and investigators. In addition, as this is a feasibility study, it is important to replicate the methodology that will eventually be used with a larger trial in order to truly assess whether the intervention and methodology are acceptable, feasible and efficacious.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: taVNS Treatment<br>n = 20 | Device: taVNS<br>* The non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) device that will be used in this study is a wearable TENS unit called the Vorso STIM100 System. The Vorso system consists of a wearable, external stimulator, a neural interface ear piece, and an arm band designed to be safe for human contact. The external stimulator generates electrical pulses that are transcutaneously delivered to the auricular branch of the vagus nerve through the ear canal. The ear piece contains 4 electrodes that carry current from the external stimulator to the auricular branch of vagus nerve. The external stimulator connects to a flexible arm band that attaches to the upper arm for ease of use during each stimulation session. The type of stimulation (including shape, frequency, pulse width, amplitude, total charge, and energy delivered) is comparable to the levels applied by commercially available TENS stimulators. The sham control group will not receive any stimulation.<br>|
| Sham Comparator: Sham Comparator<br>n = 10 | Device: taVNS<br>* The non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) device that will be used in this study is a wearable TENS unit called the Vorso STIM100 System. The Vorso system consists of a wearable, external stimulator, a neural interface ear piece, and an arm band designed to be safe for human contact. The external stimulator generates electrical pulses that are transcutaneously delivered to the auricular branch of the vagus nerve through the ear canal. The ear piece contains 4 electrodes that carry current from the external stimulator to the auricular branch of vagus nerve. The external stimulator connects to a flexible arm band that attaches to the upper arm for ease of use during each stimulation session. The type of stimulation (including shape, frequency, pulse width, amplitude, total charge, and energy delivered) is comparable to the levels applied by commercially available TENS stimulators. The sham control group will not receive any stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Utilizing taVNS with WTCHP Responders as Measured By Rates of Recruitment | Evaluated as: (1) rates of recruitment (per month) All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Feasibility of Utilizing taVNS with WTCHP Responders as Measured By Intervention Adherence | Evaluated as: (2) adherence to the taVNS intervention All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Feasibility of Utilizing taVNS with WTCHP Responders as Measured By Retention Rates | Evaluated as: (3) 8-week retention All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Feasibility of Utilizing taVNS with WTCHP Responders as Measured By Duration | Evaluated as: (4) duration of study assessments All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Feasibility of Utilizing taVNS with WTCHP Responders as Measured By Completion Rates | Evaluated as: (5) completion rate of study assessments All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability of taVNS by WTCHP Responders As Assessed by Time to Completion of Questionnaires and Biological Data | Assessing: (1) the time to completion of questionnaires and biological data/blood draw All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Acceptability of taVNS by WTCHP Responders As Assessed by Percentage Missing Data | Assessing: (2) percentage of missing data from questionnaires All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Acceptability of taVNS by WTCHP Responders As Assessed by Rate of Refusal | Assessing: (3) the rate of refusal of biologic measurements and blood draw All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 
| Acceptability of taVNS by WTCHP Responders As Assessed by Score of taVNS Satisfaction and Usefulness Questionnaire | Assessing: (4) the score on the taVNS Satisfaction and Usefulness Questionnaire All measures will be described using frequency and percent or mean (SD) as appropriate, overall and by taVNS and sham group, with corresponding 95% confidence intervals to interpret the precision of the estimates. Median and interquartile range may also be used if discrete data are skewed. | 8 week follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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feasibility and acceptability, WTC responders, taVNS