DepressionNCT05725239
taVNS or TMS or Both for Depression
A study testing Vagus Nerve Stimulation and Transcranial Magnetic Stimulation in people with Depression, run by Medical University of South Carolina at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Depression
- What is being tested?
- Vagus Nerve Stimulation and Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Mar 2023to 1 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Medical University of South Carolina Institute of Psychiatry
Charleston, South Carolina, 29412
Mark George, georgem@musc.edu
Elisabeth Collins, collieli@musc.edu
About this study
Official title: 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.
- Conditions
- Depression
- Being tested
- Vagus Nerve Stimulation, Transcranial Magnetic Stimulation
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagus Nerve StimulationDevice
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.
Transcranial Magnetic StimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Vagus Nerve Stimulation (VNS) only | Experimental | Not described Receives: Device: Vagus Nerve Stimulation |
| Transcranial Magnetic Stimulation (TMS) only | Experimental | Not described Receives: Device: Transcranial Magnetic Stimulation |
| Synchronized VNS and TMS | Experimental | Not described Receives: Device: Vagus Nerve Stimulation; Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Through study completion, an average of 8 weeks
Secondary outcomes (2)
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.
Measured: 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.
Measured: One month following conclusion of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2023
- Study start14 Mar 2023
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark George, Medical University of South Carolina
- Investigators
- Mark George, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05725239
- Sponsor's protocol ID
- 00125468
- Status last verified
- Jul 2026
- First submitted
- 18 Jan 2023
- Last updated
- 12 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synchronized Cervical or Auricular VNS With Prefrontal rTMS for Treatment Resistant Depression (TRD)
- ClinicalTrials.gov ID
- NCT05725239
- Acronym / sponsor ID
- 00125468
- Conditions
- Depression
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- 14 Mar 2023 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 13 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vagus Nerve StimulationAll 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 | Synchronized VNS and TMS, Vagus Nerve Stimulation (VNS) only |
| Transcranial Magnetic StimulationParticipants 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. | Device | Synchronized VNS and TMS, Transcranial Magnetic Stimulation (TMS) only |
Primary outcome
Change in Hamilton Depression Rating Scale
Time frame: Through study completion, an average of 8 weeks
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.
Change in Patient Health Questionnaire 9
Time frame: Through study completion, an average of 8 weeks
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.
2 secondary outcomes
Number of adverse outcomes
Time frame: One week following conclusion of the trial
Number of adverse outcomes
Time frame: One month following conclusion of the trial
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mark George, MD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vagus Nerve Stimulation and Transcranial Magnetic Stimulation in people with Depression, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mark George (843-876-5142, georgem@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hamilton Depression Rating Scale (time frame: Through study completion, an average of 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.