taVNS or TMS or Both for Depression

NCT05725239 | Recruiting FDA Device

• 1 other identifier: 00125468
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depression

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Number of adverse outcomes

  One week following conclusion of the trial

• Number of adverse outcomes

  One month following conclusion of the trial

Study Arms (3)

Vagus Nerve Stimulation (VNS) only

EXPERIMENTAL

Device: Vagus Nerve Stimulation

Transcranial Magnetic Stimulation (TMS) only

EXPERIMENTAL

Device: Transcranial Magnetic Stimulation

Synchronized VNS and TMS

EXPERIMENTAL

Device: Vagus Nerve Stimulation; Device: Transcranial Magnetic Stimulation

Interventions

Vagus Nerve Stimulation DEVICE

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.

Synchronized VNS and TMS; Vagus Nerve Stimulation (VNS) only

Transcranial Magnetic Stimulation DEVICE

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.

Synchronized VNS and TMS; Transcranial Magnetic Stimulation (TMS) only

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• item Hamilton Depression Rating Scale (HAM-D) score ≥20
• Not responding to talking therapy.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina Institute of Psychiatry

Charleston, South Carolina, 29412, United States

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Vagus Nerve Stimulation; Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Magnetic Field Therapy

Study Officials

• Mark George, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark George

CONTACT

843-876-5142; georgem@musc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: February 13, 2023
• Study Start: March 14, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)