A total of up to 90 distressed persons who work in health care and health care providers in the Philadelphia, PA region, will be screened for this study. From that group, the researchers plan to enroll enough subjects to have 80 fully complete the study. The 90 screened subjects will allow for screen failures and subjects who withdraw early from the study. All subjects will receive an initial evaluation using symptom questionnaires (these will include the Global Severity Index of the Brief Symptom Inventory-18 which is the primary outcome, and secondary outcomes as measured by the Maslach Burnout Scale, GAD-7 (anxiety), PHQ-9 (depression), the Connor Davidson Resilience Scale-25 (CD-RISC), and the Insomnia Severity Index (ISI) and physiological measures that will consist of heart rate variability (HRV) and galvanic skin resistance (GSR). Subjects will then be randomized to either the 3 month TaVNS program or the 3 month waitlist group. At one month, subjects will receive a follow up request to complete the same questionnaires as in the initial evaluation for an interim evaluation. Then after receiving the TaVNS program or being in the waitlist control group for 3 months, the subjects will have a repeat of the questionnaires and physiological testing. Subjects in the waitlist group will then be provided the TaVNS program to be used for 3 months. This group will be asked to complete one final set of symptom questionnaires at the completion of using the TaVNS program.
Two subgroups will be included in fMRI scans performed during the initial evaluation period (pre) and at 3 months (post). Subgroup I of 30 subjects (15 in TaVNS group and 15 in waitlist control) will undergo fMRI scans that will include structural imaging and functional imaging with Blood Oxygen Level Dependent Imaging (BOLD) scan and arterial spin labeling (ASL) scans. Specifically, during the ASL scans (each approximately 5 minutes long), a script of the subject's most distressing recollection(s) will be read from an audio file script while each subject is in the MRI scanner. Changes in brain function will be compared between the stress script and a neutral script (that describes a typical morning waking up). This same imaging protocol, which takes a total of about 45 minutes, will be performed initially and then after the 3 month TaVNS program or the waitlist period. All scans will be co-registered and comparable slices of the cerebral cortex will be examined.
Subgroup II will consist of 10 study subjects all receiving the TaVNS program who will undergo fMRI initially and then again at 3 months. This group will be scanned while wearing the TaVNS system (a special one that can be used in the MRI environment) and the fMRI will be used to evaluate the direct effects of the TaVNS while turned on and off in the scanner. The imaging protocol will take a total of about 45 minutes. In addition to the 10 study subjects, the researchers will also plan to recruit 10 healthy controls with no reports of psychological distress (i.e. less than 2 on the SUDS). These 10 healthy controls will have the TaVNS placed while receiving two fMRI scans approximately 3 months apart. These control subjects will be used to compare the subgroup of study subjects to ensure that any changes are not associated with test-retest effects.
The subgroups will be filled with eligible and interested subjects. If the subject is interested and is able to undergo fMRI scanning, the subject will be placed in Subgroup I until enrollment is filled and then subsequently subjects will be enrolled into Subgroup II until enrollment is filled. Any eligible subject that is unwilling or unable to undergo fMRI scanning will be placed in the general, non-scanning group. Once the two subgroups are filled, any remaining eligible subjects will be placed in the general, non-scanning group.
Substudy:
A total of 50 additional subjects will be screened to receive one MRI imaging while using the TaVNS earbuds. Subjects who are eligible to receive an MRI scan will be enrolled from the geographical region. Participants may also be self-referred by responding to flyers to inquire more about the study. The objective of the substudy (Subgroup III) is to increase our understanding of the mechanisms and neurophysiological response while using the TaVNS in the MRI scanner by evaluating cerebral blood and activation states while the TaVNS is "on" and "off" during a single fMRI session while using the TaVNS.
Endpoints for the Imaging Using TaVNS Substudy
A substudy (Subgroup III) of 50 subjects, with no randomization, will undergo fMRI scans with the TaVNS system being turned on and off while in the scanner to observe for any immediate effects. While the system is generally not supposed to be used in the MRI environment, a special non-magnetic version (that can be used in the MRI environment) will be used to test this change. Specifically, the unit itself will be outside of the MRI environment and will be attached to the earbuds using a non-magnetic wire.
Secondary Endpoints:
Secondary endpoints may include clinical measures including the Maslach Burnout Scale, GAD-7 (anxiety), PHQ-9 (depression), Connor Davidson Resilience Scale-25 (CD-RISC), Insomnia Severity Index (ISI), and physiological measures that will consist of heart rate variability (HRV) and blood pressure.
Additional secondary endpoints will be the baseline fMRI scans that will include structural imaging and functional imaging with Blood Oxygen Level Dependent Imaging (BOLD) scan and two arterial spin labeling (ASL) scans. fMRI scan data for this substudy may be compared between the MRI Imaging group and the TaVNS group and waitlist control.
Subgroup II will consist of 10 study subjects all receiving the TaVNS program who will undergo fMRI initially and then again at 1 month (+30 days). This group will be scanned while wearing the TaVNS system (a special one that can be used in the MRI environment) and the fMRI will be used to evaluate the direct effects of the TaVNS while turned on and off in the scanner. The imaging protocol will take a total of about 45 minutes.
In addition to the 10 study subjects in the distressed workers group, we intend to recruit 50 healthy controls with no reports of psychological distress (i.e. less than 2 on the SUDS) with no biofeedback evaluation. These 50 healthy controls will have the TaVNS placed while receiving one fMRI scans. These control subjects will be used to compare the subgroup of study subjects to understand the changes in the brain while using the TaVNS. These participants will be consented with an informed consent form that describes the substudy in more detail. Subjects in the substudy Group III will receive only one fMRI imaging session on one day and will be asked to complete surveys. Participants in this substudy will have heart rate collected at baseline, during and after the fMRI while using the VNS.
All subjects will receive an initial evaluation using symptom questionnaires (these will include the Global Severity Index of the Brief Symptom Inventory-18 which is the primary outcome, and secondary outcomes as measured by the Maslach Burnout Scale, GAD-7 (anxiety), PHQ-9 (depression), the Connor Davidson Resilience Scale-25 (CD-RISC), and the Insomnia Severity Index (ISI).
The eligibility for imaging is the same for all groups with the exception of Subjective Units of Distress Scores.
