Rapid Antidepressant Dynamics in Acute Neuromodulation Treatments

NCT ID: NCT06976840

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2030-08-01

Brief Summary

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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.

Detailed Description

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This mechanistic clinical trial will investigate the role of large-scale brain networks in modulating mood responses in adults with major depressive disorder (MDD) using non-invasive neuromodulation and neuroimaging. The study will focus on the salience network (SN), default mode network (DMN), and functional connectivity (FC) between them, given prior evidence linking these systems to mood regulation and antidepressant response.

Using a 2x3 factorial design, 200 participants with MDD will be randomized to receive theta burst stimulation (TBS) targeting either the SN or the DMN (between-subject factor). Each participant will complete three within-subject TBS sessions one week apart: intermittent TBS (iTBS), continuous TBS (cTBS), and sham stimulation. TBS will be delivered over individualized fMRI-based targets derived from prior resting-state connectivity maps.

Following each stimulation session, participants will complete an MRI protocol that includes administration of either a fast-acting or conventional antidepressant, as well as resting-state functional imaging.

Primary neural outcomes include changes in activation and connectivity within and between SN and DMN regions, measured using task-based and resting-state fMRI. Behavioral outcomes include mood ratings acquired repeatedly during the scanning session and via daily remote assessments for one week post-stimulation.

This design allows for within-subject comparison of the acute and sub-acute effects of different TBS patterns, and between-subject comparison of SN- vs. DMN-targeted stimulation. The study aims to identify brain circuits that can be engaged or modulated to enhance treatment response in depression, with the longer-term goal of informing precision neuromodulation strategies.

Note: Certain information is withheld to protect the scientific integrity of the study design.

Conditions

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Depression Major Depressive Disorder

Keywords

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theta burst stimulation reinforcement learning neuroimaging

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

This is a mechanistic trial
Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Salience Network Target

Intermittent/Sham/Continuous TBS, counterbalanced in order.

Group Type OTHER

Intermittent theta burst stimulation

Intervention Type DEVICE

Aimed at potentiating the stimulation target.

Sham theta burst stimulation

Intervention Type DEVICE

No effect is expected on stimulation target

Continuous theta burst stimulation

Intervention Type DEVICE

Aimed at depotentiating the stimulation target

Default Mode Network Target

Intermittent/Sham/Continuous TBS, counterbalanced in order.

Group Type EXPERIMENTAL

Intermittent theta burst stimulation

Intervention Type DEVICE

Aimed at potentiating the stimulation target.

Sham theta burst stimulation

Intervention Type DEVICE

No effect is expected on stimulation target

Continuous theta burst stimulation

Intervention Type DEVICE

Aimed at depotentiating the stimulation target

Interventions

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Intermittent theta burst stimulation

Aimed at potentiating the stimulation target.

Intervention Type DEVICE

Sham theta burst stimulation

No effect is expected on stimulation target

Intervention Type DEVICE

Continuous theta burst stimulation

Aimed at depotentiating the stimulation target

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. being pregnant or breastfeeding;
2. diagnosis of psychotic depression, schizophrenia, bipolar disorder, or other Axis I disorders, except for anxiety disorders;
3. 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;
4. requiring immediate hospitalization;
5. epilepsy or conditions requiring an anticonvulsant;
6. receiving vagus nerve stimulation, electroconvulsive therapy (ECT), or TMS in the last 2 months;
7. currently taking or have taken within the last 21 days psychiatric medication or augmenting agents;
8. receiving depression-specific psychotherapy;
9. actively suicidal or considered a high suicide risk;
10. enrolled in another study; or
11. MRI/TMS contraindication as determined by the fMRI and TMS screening questionnaires
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Marta Peciña, MD PhD

OTHER

Sponsor Role lead

Responsible Party

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Marta Peciña, MD PhD

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Marta Pecina, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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Bellefield Towers

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Central Contacts

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Eli Strohecker, BS

Role: CONTACT

Phone: 412-246-6147

Email: [email protected]

Gaurav Badhan, BS

Role: CONTACT

Email: [email protected]

Facility Contacts

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Eli Strohecker, BS

Role: primary

Gaurav Badhan, BS

Role: backup

Other Identifiers

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STUDY24040131

Identifier Type: -

Identifier Source: org_study_id