Clinical trial NCT06976840: Rapid Antidepressant Dynamics in Acute Neuromodulation Treatments
Official title: Rapid Antidepressant Dynamics in Acute Neuromodulation Treatments
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Depression
Major Depressive Disorder
Keywords: theta burst stimulation
reinforcement learning
neuroimaging
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2025-05-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This is a mechanistic trial
Primary purpose: OTHER

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Bold Signal Change in the Salience Network During the fMRI Experiment
timeFrame: Assessed at approximately day 7, day 14, and day 21 following baseline.
measure: BOLD Signal Change in the Default Mode Network During the fMRI Experiment
timeFrame: Assessed at approximately day 7, day 14, and day 21 following baseline.
measure: Changes in Mood Ratings Following TBS and the fMRI Experiment
timeFrame: Baseline
measure: Subcute Mood Change Following TBS and the fMRI experiment
timeFrame: Approximately at day 7, 14, and 21
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Bellefield Towers
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Marta Pecina, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: