NCT06976840

Brief Summary

The goal of this clinical trial is to learn how different types of non-invasive brain stimulation affect mood and brain function in adults with major depressive disorder (MDD). It will also study how brain stimulation may work together with antidepressant treatments. The main questions this study aims to answer are: How do different patterns of brain stimulation affect mood in people with depression? Do brain networks involved in emotion and self-reflection respond differently depending on the type of stimulation? What are the combined effects of brain stimulation and antidepressant treatments on mood and brain activity? Researchers will compare different brain stimulation patterns and target areas to understand their individual and combined effects. Participants will: Receive three types of brain stimulation (intermittent, continuous, and sham) in different sessions Undergo MRI scans during the administration of either a fast-acting or conventional antidepressant. Complete mood assessments during the scan and for one week after each session This study may help identify brain-based strategies to improve treatment for depression. In addition, a subset of participants (\~10) will complete a reward-guided decision-making fMRI task for feasibility purposes.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P50-P75 for not_applicable depression

Timeline
52mo left

Started May 2026

Longer than P75 for not_applicable depression

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 30, 2025

Completed
16 days until next milestone

First Posted

Study publicly available on registry

May 16, 2025

Completed
12 months until next milestone

Study Start

First participant enrolled

May 1, 2026

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2030

Last Updated

May 6, 2026

Status Verified

November 1, 2025

Enrollment Period

4.3 years

First QC Date

April 30, 2025

Last Update Submit

May 4, 2026

Conditions

Keywords

theta burst stimulationreinforcement learningneuroimaging

Outcome Measures

Primary Outcomes (4)

  • Bold Signal Change in the Salience Network During the fMRI Experiment

    Change in blood oxygenation level-dependent (BOLD) signal within the salience network (SN), measured during the fMRI experiment. Comparisons is made across transcranial magnetic stimulation conditions: intermittent theta burst stimulation (iTBS) vs. sham TBS (sTBS), and continuous TBS (cTBS) vs. sTBS. SN activation is assessed using fMRI contrasts sensitive to expectancy-induced neural modulation.

    Assessed at approximately day 7, day 14, and day 21 following baseline.

  • BOLD Signal Change in the Default Mode Network During the fMRI Experiment

    Change in blood oxygenation level-dependent (BOLD) signal within the default mode network (DMN), measured during the fMRI experiment. Comparisons is made across transcranial magnetic stimulation conditions: intermittent theta burst stimulation (iTBS) vs. sham TBS (sTBS), and continuous TBS (cTBS) vs. sTBS. DMN activation is assessed using fMRI contrasts sensitive to expectancy-induced neural modulation.

    Assessed at approximately day 7, day 14, and day 21 following baseline.

  • Changes in Mood Ratings Following TBS and the fMRI Experiment

    Change in self-reported mood, coded as a binary indicator of perceived mood improvement (yes/no), is assessed after each TBS session (iTBS, cTBS, sTBS) during the fMRI task. Participants are considered to show mood improvement if their post-stimulation average mood rating across trials increased relative to baseline. Between-condition comparisons (iTBS vs. sTBS; cTBS vs. sTBS) are conducted to evaluate the acute effects of TBS on mood reactivity.

    Baseline

  • Subcute Mood Change Following TBS and the fMRI experiment

    Change in depressive symptoms is assessed using the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16; range: 0-27), where higher scores indicate greater depressive symptom severity. The QIDS-SR16 evaluates core domains of depression, including mood, interest, sleep, appetite, and concentration, over the past 7 days. Between-session changes (baseline to days 7, 14, and 21) are analyzed to assess subacute mood effects of intermittent TBS (iTBS), continuous TBS (cTBS), and sham TBS (sTBS) and the fMRI experimental manipulation.

    Approximately at day 7, 14, and 21

Study Arms (2)

Salience Network Target

OTHER

Intermittent/Sham/Continuous TBS, counterbalanced in order.

Device: Intermittent theta burst stimulationDevice: Sham theta burst stimulationDevice: Continuous theta burst stimulation

Default Mode Network Target

EXPERIMENTAL

Intermittent/Sham/Continuous TBS, counterbalanced in order.

Device: Intermittent theta burst stimulationDevice: Sham theta burst stimulationDevice: Continuous theta burst stimulation

Interventions

Aimed at potentiating the stimulation target.

Default Mode Network TargetSalience Network Target

No effect is expected on stimulation target

Default Mode Network TargetSalience Network Target

Aimed at depotentiating the stimulation target

Default Mode Network TargetSalience Network Target

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Adults ages 18-55 (\~60% female).
  • Diagnosis of Major Depressive Disorder (MDD) with or without comorbid anxiety disorders (e.g., panic disorder) or Axis II disorders.
  • Psychotropic-free at enrollment.

You may not qualify if:

  • being pregnant or breastfeeding;
  • diagnosis of psychotic depression, schizophrenia, bipolar disorder, or other Axis I disorders, except for anxiety disorders;
  • severe substance use (excluding nicotine) in the last 2 months as determined by using the MINI, a structured interview that uses the Diagnostic and Statistical Manual of Mental Disorders;
  • requiring immediate hospitalization;
  • epilepsy or conditions requiring an anticonvulsant;
  • receiving vagus nerve stimulation, electroconvulsive therapy (ECT), or TMS in the last 2 months;
  • currently taking or have taken within the last 21 days psychiatric medication or augmenting agents;
  • receiving depression-specific psychotherapy;
  • actively suicidal or considered a high suicide risk;
  • enrolled in another study; or
  • MRI/TMS contraindication as determined by the fMRI and TMS screening questionnaires

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bellefield Towers

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

DepressionDepressive Disorder, Major

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehaviorDepressive DisorderMood DisordersMental Disorders

Study Officials

  • Marta Pecina, MD, PhD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Eli Strohecker, BS

CONTACT

Gaurav Badhan, BS

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
FACTORIAL
Model Details: This is a mechanistic trial
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

April 30, 2025

First Posted

May 16, 2025

Study Start

May 1, 2026

Primary Completion (Estimated)

August 1, 2030

Study Completion (Estimated)

August 1, 2030

Last Updated

May 6, 2026

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

Consistent with NIMH Data Archive (NDA) policies, the investigators will obtain relevant GUIDs and experiment IDs in order to upload all relevant data biannually. The investigators will use the Validation and Upload Tool for CSV files from behavior during the fMRI experiment, and NIfTI-formatted images for imaging. The investigators will upload study data cumulatively every 6 months per NDA guidelines, with the exception of imaging data, which are will be uploaded in installments. The final research data will not contain any identifiable information and will be deposited in the NIMH Data Archive (NDA). While data is submitted biannually, the complete dataset will be made available for sharing with the research community 24 months after the original study end date. Furthermore, the specific data used for primary analyses will be shared via an NDA Study DOI prior to the acceptance for publication of the main findings.

Shared Documents
STUDY PROTOCOL
Time Frame
Supporting documentation, including the Study Protocol, Statistical Analysis Plan, Informed Consent Form, and Analytic Code, will be made available upon reasonable request from the journal or other investigators. Furthermore, analytic code and study protocols will be provided as supplemental material at the time of publication of the main findings as deemed appropriate.
Access Criteria
Anyone who wishes to access the data.

Locations