taVNS or TMS or Both for Depression

Study Overview
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Brief Summary
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The purpose of the research is to test out a combined treatment for depression where the investigators stimulate a nerve in the ear while at the same time stimulate the brain with magnets. These treatments are called transcutaneous (through the skin) auricular (ear) vagus nerve stimulation (taVNS) and transcranial (through the skull) magnetic stimulation (TMS). For participants who already have a cervical VNS device, the investigators will not change their treatment and will use this in place of the taVNS. The investigators think this combined method might treat depressive symptoms better than either alone. This study is in person at the Institute of Psychiatry in downtown Charleston on the MUSC campus. First, participants will have a screening session and then will have 6 treatment days total where participants will receive either VNS treatment alone, TMS treatment alone, or both at the same time. The treatment that participants start with will be randomized, and they will have 2 treatment days of each combination.

Official Title
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Synchronized Cervical or Auricular VNS With Prefrontal rTMS for Treatment Resistant Depression (TRD)

Conditions
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Depression

Intervention / Treatment
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* Device: Vagus Nerve Stimulation
* Device: Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old Undergoing cervical VNS or have tried and failed two antidepressant medications in the current episode Able to provide informed consent English speaking and can read and write 17-item Hamilton Depression Rating Scale (HAM-D) score ≥20 Not responding to talking therapy. Exclusion Criteria: Preexisting neurological disorders, or dementia History of major head trauma Life expectancy <1 year Any type of cognitive impairment that would require approval/signature of a legal guardian/representative for participation A score of >2 on question 3 of the Hamilton Depression Rating pertaining to suicidality Current active suicidal intent or plan, prior attempt within the last 6 months, or who in the judgment of the investigator would be at elevated risk for suicide will be excluded Patients who are pregnant will also be excluded. We will require a pregnancy test for individuals of child-bearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vagus Nerve Stimulation (VNS) only<br> | Device: Vagus Nerve Stimulation<br>* All taVNS sessions will use the following parameters: 25Hz, 500us pulse width, on for 7 seconds, off for 12 seconds.The length of VNS treatment sessions will be identical to TMS treatment sessions and will have the same 30 minute break between each treatment session. These treatments (active or sham) will be administered to participants each treatment day, for a total of 6 different treatment days, but only 4 are active.<br>|
| Experimental: Transcranial Magnetic Stimulation (TMS) only<br> | Device: Transcranial Magnetic Stimulation<br>* Participants will receive 20 trains of 30 pulses each for a total of 600 pulses per session. We will repeat this for 6 sessions each day, with at least 30 minutes between each session. These treatments (active or sham) will be administered to participants each treatment day, for a total of 6 different treatment days, but only 4 are active, so participants will get 24 TMS sessions over the course.<br>|
| Experimental: Synchronized VNS and TMS<br> | Device: Vagus Nerve Stimulation<br>* All taVNS sessions will use the following parameters: 25Hz, 500us pulse width, on for 7 seconds, off for 12 seconds.The length of VNS treatment sessions will be identical to TMS treatment sessions and will have the same 30 minute break between each treatment session. These treatments (active or sham) will be administered to participants each treatment day, for a total of 6 different treatment days, but only 4 are active.<br>Device: Transcranial Magnetic Stimulation<br>* Participants will receive 20 trains of 30 pulses each for a total of 600 pulses per session. We will repeat this for 6 sessions each day, with at least 30 minutes between each session. These treatments (active or sham) will be administered to participants each treatment day, for a total of 6 different treatment days, but only 4 are active, so participants will get 24 TMS sessions over the course.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale | The Hamilton Depression Rating Scale (HDRS) is a commonly used clinician-administered depression rating scale to assess severity of depressive symptoms. The HDRS has a possible score range of 0-52. The higher the HDRS score, the more severe the depressive symptoms are in that patient. | Through study completion, an average of 8 weeks | 
| Change in Patient Health Questionnaire 9 | The Patient Health Questionnaire 9 (PHQ-9) is a brief self-administered questionnaire to assess depressive symptoms. The PHQ-9 has a possible score range of 0-27. The higher the PHQ-9 score, the more severe the depressive symptoms are in that patient. | Through study completion, an average of 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse outcomes | Participants will be called at the 1 week and 1 month timepoints following their completion of the trial to inquire about any adverse outcomes they have experienced, if any, since the conclusion of the trial as a means of measuring feasibility of the treatment. | One week following conclusion of the trial | 
| Number of adverse outcomes | Participants will be called at the 1 week and 1 month timepoints following their completion of the trial to inquire about any adverse outcomes they have experienced, if any, since the conclusion of the trial as a means of measuring feasibility of the treatment. | One month following conclusion of the trial |