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

NCT06376734 | Recruiting Phase 2 DMC

• 1 other identifier: 2024p000528
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Obsessive-Compulsive Disorder; Generalized Anxiety Disorder; Mood Disorders; Psychiatric Disorder; Mental Disorder; Depression, Anxiety; Schizophrenia; Major Depressive Disorder

Keywords

depression; anxiety; schizophrenia; OCD; obsessive-compulsive disorder; transcranial magnetic stimulation; TMS; accelerated TMS; accelerated intermittent theta burst stimulation; brain stimulation; neuromodulation; transdiagnostic; neuronavigation; functional connectivity; neuroimaging; theta burst stimulation

Outcome Measures

Primary Outcomes (1)

• Clustering of multiple behavioral measures

  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

Study Arms (3)

TMS to random PFC location 1

EXPERIMENTAL

Participants will receive 2 days of accelerated TMS (10 treatments per day) to a random location in the prefrontal cortex.

Device: Transcranial magnetic stimulation

TMS to random PFC location 2

EXPERIMENTAL

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

TMS to Schizophrenia location

EXPERIMENTAL

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

Interventions

Transcranial magnetic stimulation DEVICE

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.

TMS to Schizophrenia location; TMS to random PFC location 1; TMS to random PFC location 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Acacia Clinics

Sunnyvale, California, 94087, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Obsessive-Compulsive Disorder; Schizophrenia; Generalized Anxiety Disorder; Mood Disorders; Mental Disorders; Depression; Anxiety Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Schizophrenia Spectrum and Other Psychotic Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Shan H Siddiqi, MD

  Brigham and Women's

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily Aquadro, MD

CONTACT

857-307-0294; expedition@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: All participants will receive real open-label TMS, so there will be no conventional masking. However, participants and investigators will be blinded to which network is being stimulated.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Double-blind, randomized controlled crossover trial. Participants will be stimulated at a random location in the prefrontal cortex, which will be mapped to its underlying brain network to determine which network was stimulated.

Study Record Dates

• First Submitted: March 31, 2024
• First Posted: April 19, 2024
• Study Start: January 30, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (2)