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

NCT ID: NCT06376734

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-30
• Study Completion Date: 2030-06-01

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation

Intervention Type: 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 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.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shan Siddiqi, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shan H Siddiqi, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's

Locations

Acacia Clinics

Sunnyvale, California, United States

Site Status: NOT_YET_RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Emily Aquadro, MD

Role: CONTACT

expedition@mgb.org

857-307-0294

Facility Contacts

Danielle DeSouza, PhD

Role: primary

expedition@mgb.org

857-307-0294

Emily Aquadro, MD

Role: primary

expedition@mgb.org

857-307-0294

Other Identifiers

2024p000528

Identifier Type: -

Identifier Source: org_study_id