Recruiting

RECOVERS

Sponsor:

Medical University of South Carolina

Code:

NCT05977439

Conditions

Depression

Major Depressive Disorder

Suicidal Ideation

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Single-Pulse Transcranial Magnetic Stimulation

EEG-Synchronized Repetitive Transcranial Magnetic Stimulation (rTMS)

Cognitive Behavioral Therapy (CBT)

Cognitive Flexibility and Emotion Regulation Tasks

Study Details

Brief summary:

In this research study, investigators examine how brain activity changes during tests of emotional processing, attention, and memory using multimodal neuroimaging methods including electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). Transcranial magnetic stimulation (TMS) is used to probe and modulate brain networks related to cognitive flexibility and emotion regulation.

The study includes multiple related sub-studies involving healthy participants and participants with depression. Some study components focus on mechanistic modeling using non-therapeutic neurostimulation in healthy participants, while other components include interventional approaches such as individualized EEG-synchronized repetitive TMS (rTMS), cognitive tasks, and brief cognitive behavioral therapy (CBT) in participants with depression. Certain study components also evaluate CBT alone without TMS to assess behavioral intervention effects.

Conditions

Depression

Major Depressive Disorder

Suicidal Ideation

Study ID

NCT05977439

Start date

Feb 1, 2024

Status verified date

Jul, 2026

Completion date

Oct 1, 2028

Anticipated

Primary completion date

Oct 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Study 1 (Healthy Participants)

Inclusion Criteria:

  • Age 18-65 years
  • Medically and psychiatrically healthy with no history of psychiatric or neurological disorders
  • English-speaking
  • Capacity to provide informed consent
  • Willingness and ability to complete study procedures
  • Negative pregnancy test for participants of childbearing potential

Exclusion Criteria:

  • Any current or past psychiatric diagnosis
  • Neurological disorders or history of central nervous system disease
  • History of seizure or epilepsy or use of medications that lower seizure threshold
  • Significant head injury or loss of consciousness
  • Implanted metal or contraindications to MRI or TMS
  • Substance use disorder (excluding nicotine or caffeine)
  • Pregnancy or plans to become pregnant during study participation
  • Inability to complete study procedures

Studies 2, 3, and 4 (Participants With Depression)

Inclusion Criteria:

  • Age 18-65 years
  • Current diagnosis of Major Depressive Disorder (MDD)
  • Depression severity consistent with study criteria (e.g., HAM-D ≥17)
  • No history of psychotic or bipolar disorders
  • English-speaking
  • Capacity to provide informed consent
  • Willingness and ability to complete study procedures
  • Negative pregnancy test for participants of childbearing potential

Exclusion Criteria:

  • Neurological disorders or history of central nervous system disease
  • History of seizure or epilepsy or use of medications that lower seizure threshold
  • Significant head injury or loss of consciousness
  • Implanted metal or contraindications to MRI or TMS
  • Substance use disorder (excluding nicotine or caffeine)
  • Current participation in another interventional clinical trial
  • Pregnancy or plans to become pregnant during study participation
  • Any condition that would interfere with safe participation or completion of study procedures

Study Design

Enrollment

120 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Healthy Participants (Study 1)

Healthy adult participants with no history of psychiatric or neurological illness who undergo mechanistic and modeling procedures, including multimodal neuroimaging, behavioral cognitive tasks, and nontherapeutic neurostimulation, to characterize brain networks underlying cognitive flexibility and emotion regulation.

experimental: Depressed Participants - EEG-Synchronized rTMS (Studies 2 and 3)

Participants with major depressive disorder who receive individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS), delivered alone or in combination with cognitive tasks and/or brief cognitive behavioral therapy (CBT), to modulate neural networks underlying cognitive flexibility and emotion regulation.

experimental: Depressed Participants - Cognitive Behavioral Therapy Only (Study 4)

Participants with major depressive disorder who receive a course of cognitive behavioral therapy (CBT) along with MRI and behavioral assessments, without transcranial magnetic stimulation or EEG-based neurostimulation. This group allows evaluation of behavioral intervention effects independent of neurostimulation.

Interventions

Single-Pulse Transcranial Magnetic Stimulation

Single-pulse transcranial magnetic stimulation delivered during EEG or neuroimaging sessions for non-therapeutic mapping of cortical excitability and functional connectivity.

EEG-Synchronized Repetitive Transcranial Magnetic Stimulation (rTMS)

Repetitive transcranial magnetic stimulation delivered using individualized, EEG-derived stimulation parameters designed to synchronize stimulation timing with participants' alpha oscillatory phase. This closed-loop approach is intended to modulate neural networks underlying cognitive flexibility and emotion regulation. Stimulation may be delivered in accelerated sessions across multiple days.

Cognitive Behavioral Therapy (CBT)

A structured, brief cognitive behavioral therapy program targeting depression and related symptoms, including cognitive restructuring, emotion regulation, and coping skill development, delivered in an accelerated format during the study period.

Cognitive Flexibility and Emotion Regulation Tasks

Behavioral tasks designed to engage and assess cognitive flexibility and emotion regulation processes, performed during or adjacent to neurostimulation sessions or as part of study assessments.

Primary outcome measure

  • Change in Hamilton Depression Rating Scale (HAM-D) Score [ Time Frame: Baseline to Day 7 ]
  • Change in Patient Health Questionnaire-9 (PHQ-9) Score [ Time Frame: Baseline to Day 7 ]
  • Change in Suicide Cognitions (Brief Suicide Cognitions Scale [B-SCS]) [ Time Frame: Baseline to Day 7 ]

Central Contacts and Locations

Central contacts

Lisa McTeague, PhD

843-792-8274MCTEAGUE@MUSC.EDU

Jayce Doose

recovers@musc.edu

Locations

Medical Univeristy of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Lisa M McTeague, PhD

843-792-8274mcteague@musc.edu

Christina Marsicano

chm275@musc.edu

More Information

Sponsor

Medical University of South Carolina

Last update posted

Jul 21, 2026

Last verified

Jul, 2026

Keywords

  • transcranial magnetic stimulation
  • EEG-synchronized rTMS
  • closed-loop neurostimulation
  • depression
  • suicide prevention
  • cognitive behavioral therapy (CBT)
  • neuroplasticity

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Medical University of South Carolina on 2026-07-21.