Search for Novel Transcranial Magnetic Stimulation (TMS) Targets for Mental Illness (Expedition)

February 13, 2026 updated by: Shan Siddiqi, MD, Brigham and Women's Hospital

Transdiagnostic Circuit Mapping of Prefrontal Targets in Accelerated Transcranial Magnetic Stimulation

Participants will receive Transcranial Magnetic Stimulation (TMS) at a random location in the left prefrontal cortex, excluding sites that are potentially unsafe. Extensive behavioral testing will be conducted to determine which behaviors are modulated by stimulating which circuits.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients who meet inclusion criteria for a primary diagnosis of MDD, OCD, GAD, or Schizophrenia (n=90) and consent to treatment will be assigned two random stimulation sites in the left prefrontal cortex and receive 2 days of accelerated iTBS treatment at the first stimulation site. Patients will have a 2 month break before coming back for 2 days of accelerated iTBS treatment at the second stimulation site. Patients with schizophrenia will be offered to participate in a third arm of the trial using a schizophrenia-specific target. This arm will also include fMRI scans and behavioral testing pre- and post- aiTBS. There will be two days (6 hours total) of behavioral testing and MRI scanning before each stimulation session and two days (6 hours total) after each stimulation session. Participants will be given the option of completing the behavioral testing in one day, before and after stimulation sessions. All the patients will receive active stimulation, which will facilitate enrollment and eliminate ethical concerns about placebo treatment in vulnerable patient populations. All participants will be blinded to their target coordinates and scales will be administered by a blinded study staff.

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Sunnyvale, California, United States, 94087
        • Recruiting
        • Acacia Clinics
        • Contact:
        • Sub-Investigator:
          • Danielle DeSouza, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Contact:
        • Principal Investigator:
          • Shan Siddiqi, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-65
  • English proficiency sufficient for informed consent, questionnaires/tasks, and treatment

  • Primary diagnosis of one of the following: major depressive disorder (MDD), obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), or schizophrenia (determined by focal assessment using the Structured Clinical Interview for DSM-5)

    • ≥20 on the Beck Depression Inventory for patients with MDD
    • ≥16 on the Beck Anxiety Inventory for patients with GAD
    • ≥16 on the Yale-Brown Obsessive-Compulsive Scale for patients with OCD
    • ≥58 on the Positive and Negative Symptom Scale for patients with schizophrenia
  • Stable psychotropic medication regimen, or remain medication free, for 4 weeks prior to treatment (Medication changes during study enrollment period will be tracked for post hoc analysis).
  • Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial

Exclusion Criteria:

  • Active pregnancy as determined by a urine pregnancy test
  • Cluster B personality disorders (antisocial personality disorder, borderline personality disorder, histrionic personality disorder, narcissistic personality disorder)
  • PTSD with active, clinically significant symptoms, as determined by clinician
  • Diagnosis of Schizoaffective Disorder, Bipolar Type
  • Recent (within 4 weeks) or concurrent use of rapid-acting antidepressant agent (ketamine/esketamine/ECT)
  • Ferromagnetic metallic implant that would contraindicate receiving TMS or obtaining MRI
  • Any other TMS or MRI safety concerns identified by the clinician
  • Receiving or planning to receive other TMS treatments during course of participation

  • History of:

    • Neurosurgical intervention for mental illness
    • Moderate to severe autism spectrum disorder
    • Intellectual disability
    • Severe cognitive impairment
    • Significant neurological illness (e.g., dementia, Parkinson's, Huntington's, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis)
    • Untreated or insufficiently treated endocrine disorder
    • Eating disorders
    • Treatment with investigational drug or intervention during the study period

  • Current evidence of:

    • Mania or hypomania
    • Active suicidal ideation or a suicide attempt within the past year
    • Contraindications to either TMS or MRI (e.g., metallic implants, etc.).
    • Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
    • Significantly increased seizure risk as determined by a clinician

  • For participants with schizophrenia:

    • Evidence of impaired capacity to consent, e.g. impaired insight into illness, as deemed by a licensed psychiatrist or psychologist on the study team
    • Hospitalization with psychosis in the past 6 months
  • Positive urine drug screen for illicit substances
  • Existing tinnitus (ringing in the ears)
  • Any other condition deemed by the PI to interfere with the study or increase risk to the participant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMS to random PFC location 1
Participants will receive 2 days of accelerated TMS (10 treatments per day) to a random location in the prefrontal cortex.
Device: Transcranial magnetic stimulation
Accelerated TMS will be provided for 2 days using the same dosing regimen as the FDA-cleared SAINT protocol, ten 9-minute treatments per day.
Experimental: TMS to random PFC location 2
After a 2-month washout following arm 1, participants will receive another two days of accelerated iTBS treatment at a different random PFC location.
Device: Transcranial magnetic stimulation
Accelerated TMS will be provided for 2 days using the same dosing regimen as the FDA-cleared SAINT protocol, ten 9-minute treatments per day.
Experimental: TMS to Schizophrenia location
Patients with schizophrenia will be offered to participate in a third arm of the trial, during which participants will receive 2 days of accelerated iTBS to a schizophrenia-specific target.
Device: Transcranial magnetic stimulation
Accelerated TMS will be provided for 2 days using the same dosing regimen as the FDA-cleared SAINT protocol, ten 9-minute treatments per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clustering of multiple behavioral measures
Time Frame: through study completion, average of 3 months

The primary outcome is that stimulation of different circuits will selectively modify different behavioral clusters. Participants will complete the following phenotyping battery tasks and questionnaires:

Q-SCID PANSS SAPS SANS PYRATS CDSS YBOCS CGI ATQ ASI BAI BDI BIS/BAS Claremont Purpose Scale De Jong Gierveld Loneliness Scale Daily Spiritual Experience Scale Emotional Reactivity Scale Flourishing Measures Headache Impact Test HiTOP-Self Report Moral Judgment Scale Pain Screener Personal Relationship with God Scale PSQI Positive and Negative Affect Scale Ruminative Response Scale Self Compassion-Short Form Spiritual Transcendence Scale- Short Form Temporal Experience of Pleasure Scale Values and Beliefs of the American Public Altruistic Decision Task Balloon Analogue Risk Task DSIAT EEfRT MSIT ECR Time perception task TMB toolkit 5min AV recording
through study completion, average of 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Shan H Siddiqi, MD, Brigham and Women's

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2025

Primary Completion (Estimated)

June 1, 2029

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

March 31, 2024

First Submitted That Met QC Criteria

April 17, 2024

First Posted (Actual)

April 19, 2024

Study Record Updates

Last Update Posted (Actual)

February 17, 2026

Last Update Submitted That Met QC Criteria

February 13, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024p000528

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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