taVNS to Reduce PTSD Symptoms in WTC Responders

Stress Disorders, Post-Traumatic Clinical Trial

— taVNS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05212714
• Other study ID #: 21-0640
• Secondary ID: U01OH012050
• Status: Completed
• Phase: N/A
• Start date: March 31, 2022
• Est. completion date: February 15, 2024

Study information

• Verified date: April 2024
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 15, 2024
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Device:
• taVNS
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.

Locations

Country	Name	City	State
United States	Feinstein Institutes for Medical Research	Manhasset	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mental Health Measures	Tertiary outcome measures validated self-report mental health measures.; For all tertiary outcomes, descriptive statistics for each time point, as well as differences over time, will be calculated. Differences in outcomes will be assessed from the first time point at baseline and the last time point at 8 weeks, for long-term effects. Within-subject correlation of acute and long-term measures will be reported.	Baseline and 8 week follow-up
Other	PTSD	Tertiary outcome measures include the administration of the CAPS PTSD interview.; For all tertiary outcomes, descriptive statistics for each time point, as well as differences over time, will be calculated. Differences in outcomes will be assessed from the first time point at baseline and the last time point at 8 weeks, for long-term effects. Within-subject correlation of acute and long-term measures will be reported.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - Heart Rate	Tertiary outcome measures include biological measures such as heart rate.; • Heart rate/HRV (6-lead ECG, DI Powerlab) (beats/min, range=40-150); The 6-lead electrocardiogram (ECG) will be recorded from wires connected from a bio-amplifier to four foam electrodes that are adhesively attached to the left shoulder, the right shoulder, the left ankle, and the right ankle. The right ankle provides a ground, while the remaining three leads provide recordings of the electrical potentials between different sites that represent the electrical activity of the heart in real-time.; The vitals will be collected by the ADInstruments PowerLab, ADInstrument sensors for collecting human physiological signals, and corresponding Labchart software.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - Galvanic Skin Response	Tertiary outcome measures include biological measures such as galvanic skin response.; • Galvanic Skin Response (GSR electrodes, ADI Powerlab) (skin conductance in microSiemens, range=0-50mS); The vitals will be collected by the ADInstruments PowerLab, ADInstrument sensors for collecting human physiological signals, and corresponding Labchart software.; Two additional sensors are placed on the left wrist and hand of the participant. The first set records electrodermal activity (EDA) by attaching two dry, metal electrodes with Velcro attachments on two fingers, preferably the pointer and ring fingers on the dominant hand. These electrodes measure the changes in skin conductance that can reflect changes in sweat gland activity.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - Skin Temperature	Tertiary outcome measures include biological measures such skin temperature.; • Skin Temperature (Thermistor Pod, ADI Powerlab) (Celsius, range=30-35C); The vitals will be collected by the ADInstruments PowerLab, ADInstrument sensors for collecting human physiological signals, and corresponding Labchart software.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - Respiratory Rate	Tertiary outcome measures include biological measures such respiratory rate.; • Respiratory Rate (Respiratory Belt, ADI Powerlab) (breaths per minute, range=3-20BPM); The vitals will be collected by the ADInstruments PowerLab, ADInstrument sensors for collecting human physiological signals, and corresponding Labchart software.; A respiratory belt that goes around the torso will be attached to the participant and is tightened without discomfort such that breathing causes the belt to stretch, which provides inspiration (inhalation) and expiration (exhalation) times to infer respiration rate.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - Blood Pressure	Tertiary outcome measures include biological measures such as beat-to-beat blood pressure.; • Beat-to-Beat Blood Pressure (Human Non-Invasive Blood Pressure Nano Interface, ADI Powerlab) (mmHg, range=50-150mmHg); A wrist device will be placed to record non-invasive blood pressure (NIBP) from the participant's left hand. The wrist device is placed with a Velcro strap on the wrist, while a small cuff is placed on the middle finger. The wrist device provides air and power for the cuff to inflate and deflate to measure changes in blood pressure.; The vitals will be collected by the ADInstruments PowerLab, ADInstrument sensors for collecting human physiological signals, and corresponding Labchart software.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - EMG	Tertiary outcome measures include biological measures such as EMG.; • Facial & Neck Electromyography (EMG electrodes, ADI Powerlab) (millivolts, range=0-15mV); Electromyogram (EMG) will be recorded by placing foam adhesive electrodes on the participant's neck. Leads are connected from these electrodes to the same bio-amplifier as the ECG.; The vitals will be collected by the ADInstruments PowerLab, ADInstrument sensors for collecting human physiological signals, and corresponding Labchart software.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - EEG	Tertiary outcome measures include biological measures of EEG(DSI-24) (band-power dB changes, range=0-10); Electroencephalography will be collected by a DSI-24 cap developed by Wearable Sensing, which offers low noise and high signal quality of non-invasive brain recordings.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Biologic Potential Endpoints - Pupil Dilation	Tertiary outcome measures include biological measures of pupil dilation (Tobii Pro Glasses 2) (pupil diameter in mm, range=2-8mm).; The eye tracking glasses, the Tobii Pro Glasses 2 are easily wearable and mobile glasses with multiple small cameras to track gaze location and pupil size.; All biological measures will be administered at the baseline visit 10 minutes before using the device and after using the device at the 8 week follow-up visit. All data will be compiled and analyzed using MATLAB.	Baseline and 8 week follow-up
Other	Markers of Inflammation - TNFa, (IL)-1ß, IL-6, IL-10, IL-12, IL-17, CRP, cortisol, and alpha amylase	Tertiary outcome measures a blood draw to assess markers of inflammation before using the device at baseline and after using the device at the 8 week follow-up visit. Inflammatory markers include Tumour Necrosis Factor alpha (TNFa), Interleukin (IL)-1ß, IL-6, IL-10, IL-12, IL-17, C Reactive Protein (CRP), cortisol, and alpha amylase.; For all tertiary outcomes, descriptive statistics for each time point, as well as differences over time, will be calculated. Differences in outcomes will be assessed from the first time point at baseline and the last time point at 8 weeks, for long-term effects. Within-subject correlation of acute and long-term measures will be reported.	Baseline and 8 week follow-up
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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