Connectomic Targeted TMS Target for Refractory Anxiety

NCT ID: NCT06376877

Last Updated: 2024-04-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2029-02-01

Brief Summary

We will perform a randomized sham-controlled trial of aiTBS to an anxiosomatic circuit in patients with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder). 80 participants with an anxiety-related disorder (defined below) will receive 50 active or sham TMS treatments over 5 days (following the SAINT protocol, which is FDA-cleared for MDD. The primary outcome will be the BAI, with a modified recall window to reflect the short treatment interval. Participants randomized to sham will be offered an open-label crossover extension.

Detailed Description

We recently derived a novel TMS target for anxiety via lesion and brain stimulation mapping methods. We prospectively tested this target in a sample of participants with major depressive disorder (MDD) with comorbid anxiety symptoms and found that it was more effective for anxiety (median change 60.0% vs 39.8%, p=0.01) than the conventional TMS target for MDD with comorbid anxiety. While these results are promising, it remains unclear how our target works for anxiety-related disorders as opposed to MDD comorbid anxiety symptoms. Furthermore, we used conventional 10 Hz TMS, but accelerated intermittent theta burst stimulation (aiTBS) has now been shown to improve outcomes and is now an FDA approved treatment protocol. Finally, we tested the translational hypothesis that stimulating different circuits can modify different behaviors; clinical efficacy was a secondary outcome.

This double-blinded, randomized, sham-controlled aiTBS trial will test the efficacy of our novel anxiety target. 80 participants with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder) will receive 50 active or sham TMS treatments over 5 days. Changes in anxiety symptoms/processes will be assessed via validated measures (primary outcome measure: Beck Anxiety Inventory) during treatment and follow-up visits up to one-year post-treatment. Participants randomized to sham who do not respond will be offered an open-label crossover extension.

Conditions

Anxiety Disorders; Mental Disorder; Psychiatric Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Real aiTBS

Participants in this group will receive aiTBS with neuronavigation to the anxiosomatic treatment target.

Group Type: ACTIVE_COMPARATOR

Transcranial magnetic stimulation

Intervention Type: PROCEDURE

Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise.

Sham aiTBS

Participants in this group will receive sham aiTBS with neuronavigation to the anxiosomatic treatment target.

Group Type: SHAM_COMPARATOR

Sham transcranial magnetic stimulation

Intervention Type: PROCEDURE

The sham TMS coil mimics the scalp sensation of real TMS by delivering a small amount of electrical current with a pair of surface electrodes.

Interventions

Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise.

Intervention Type: PROCEDURE

Sham transcranial magnetic stimulation

The sham TMS coil mimics the scalp sensation of real TMS by delivering a small amount of electrical current with a pair of surface electrodes.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
• Diagnosis of one of the following anxiety-related disorders per Quick-SCID:

• Generalized Anxiety Disorder
• Social Anxiety Disorder
• Panic Disorder
• Posttraumatic Stress Disorder
• Obsessive Compulsive Disorder
• Moderate level of anxiety (BAI >16)
• One failed psychological or pharmacological treatment
• Stable psychiatric medication regimen for 4 weeks prior to treatment and throughout treatment
• Primary clinician (e.g. psychiatrist, psychologist, therapist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
• Agreement to abstaining from becoming pregnant from screening to two weeks after treatment (the MRI visit)

Exclusion Criteria

• • Active pregnancy as determined by a urine pregnancy test

• Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
• History of:

• Exposure to TMS within the last 3 months
• Neurosurgical intervention for psychiatric disorders
• Autism spectrum disorder, intellectual disability, or cognitive impairment that impairs capacity to consent
• Significant neurological illness deemed to increase risk from treatment
• Moderate to severe neurodegenerative disease
• Untreated or insufficiently treated endocrine disorder
• Treatment with investigational drug or intervention during the study period
• Bipolar I disorder or schizophrenia
• Anyone presenting with:

• Mania or hypomania
• Psychosis
• Active suicidal ideation with intent and a plan (defined by Columbia Suicide Severity Rating Scale)
• Contraindications to either TMS or MRI (e.g., metallic implants, severe insomnia > 4 hours per night with hypnotic, etc.).
• Current moderate or severe substance use disorder (excluding cannabis or nicotine) or demonstrating signs of acute substance withdrawal
• Positive urine drug screen for illicit substances for cocaine, amphetamines, phencyclidine, and opioids, except for prescribed medications or known medications with history of resulting in a false positive
• 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: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shan Siddiqi, MD

Assistant Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shan Siddiqi, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Emma Jones

Boston, Massachusetts, United States

Countries

United States

Central Contacts

Emma Jones

Role: CONTACT

bwhtmsanxiety@mgb.org

617-525-3536

Facility Contacts

Emma Jones

Role: primary

bwhtmsanxiety@mgb.org

Other Identifiers

2024P000900

Identifier Type: -

Identifier Source: org_study_id