taVNS or TMS or Both for Depression

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

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.

Study Overview

• Status: Recruiting
• Conditions: Depression
• Intervention / Treatment: Device: Vagus Nerve Stimulation; Device: Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mark George; Phone Number: 843-876-5142; Email: georgem@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Recruiting
      • Medical University of South Carolina Institute of Psychiatry
      • Contact: Elisabeth Collins; Email: collieli@musc.edu
      • Contact: Mark George; Email: georgem@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vagus Nerve Stimulation (VNS) only	Device: Vagus Nerve Stimulation; 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.
Experimental: Transcranial Magnetic Stimulation (TMS) only	Device: Transcranial Magnetic Stimulation; 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.
Experimental: Synchronized VNS and TMS	Device: Vagus Nerve Stimulation; 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.; Device: Transcranial Magnetic Stimulation; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Mark George, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 00125468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No