Accelerated TBS for Adolescent Suicidal Ideation

Major Depressive Disorder Clinical Trial

Official title:

A Randomized Controlled Trial of Sequential Bilateral Accelerated Theta Burst Stimulation in Adolescents With Suicidal Ideation Associated With Major Depressive Disorder

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04701840
• Other study ID #: 20-009630
• Secondary ID: R01MH124655-01
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2021
• Est. completion date: April 1, 2027

Study information

• Verified date: April 2021
• Source: Mayo Clinic
• Contact: Can Ozger
• Phone: (507) 422-2605
• Email: ozger.can[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to gather information regarding the use of a new type of transcranial magnetic stimulation (TMS) called theta burst stimulation (TBS) for suicidal ideation in adolescents with Major Depressive Disorder (MDD). The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up.

Description:

Suicide is a leading cause of death in adolescents worldwide and a substantial public health problem in the United States. Despite prior efforts, outcomes related to suicide in adolescents are not improving over the years. Standard clinical and research approaches involve prevention efforts, risk assessment, crisis intervention, and psychotherapeutic techniques. Few prior studies have focused on developing brain-based treatments and biomarkers for active suicidal ideation in adolescents with depression. Conceptually, dysregulations in prefrontal cortex gamma-aminobutyric acid (GABA) inhibitory function could lead to reduced control of suicidal thoughts and behaviors in adolescents with depression. TMS treatment protocols delivered to the prefrontal cortex modulate GABA inhibitory function, synaptic plasticity, and clinical symptoms of depression. Accelerated TMS protocols that deliver theta burst stimulation TBS dosing induce synaptic plasticity changes rapidly, modulate GABA function, have rapid-acting clinical effects, and overcome the many practical limitations of standard TMS. Prior research with a biomarker of GABA activity called long-interval cortical inhibition (LICI) demonstrates potential for clinical implementation to assess suicide risk and guide treatment interventions with TMS. Electromyography (EMG) measures of LICI are easily collected and have been studied extensively in adolescents. TMS and electroencephalography (EEG) may provide more precise and sophisticated measures of GABA inhibitory function. However, there are methodologic challenges with the use of EEG measures and no prior data in adolescents with depression. This study is a randomized, double-blind, sham-controlled trial of sequential bilateral accelerated TBS (aTBS) for suicidal ideation in adolescents with MDD. All subjects in both arms will concurrently receive standard of care treatment. Three TBS sessions will be administered daily for 10 days 5 days per week for a total of 30 sessions. During each TBS session, continuous TBS is first delivered to the right dorsolateral prefrontal cortex and then intermittent TBS is delivered to the left dorsolateral prefrontal cortex. The proposed TBS parameters were adopted from prior work in adolescents. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. This study will examine the safety, feasibility, and clinical effects of sequential bilateral aTBS. In addition to the primary outcome measures, the research team will collect pre- and post-treatment LICI measures with EMG to assess suicide risk and guide treatment with TBS protocols. Concurrent measures with EEG will address an exploratory aim to further develop and refine TMS biomarkers. Existing infrastructure and collaborations will foster the rapid clinical implementation of sequential bilateral aTBS and cortical inhibition biomarkers.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: April 1, 2027
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

Inclusion Criteria:

• Inpatients or outpatients.
• Voluntary clinical patient with the capacity to assent (or consent if 18) to treatment and a parent or legal guardian with the capacity to consent (if younger than 18).
• Female or male.
• 12-18 years of age.
• Diagnosed with MDD based on Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) criteria with the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) in subjects 12-17 years of age; The Mini-International Neuropsychiatric Interview will be used for subjects who are 18 years of age.
• In a current episode of MDD with duration of at least 4 weeks but less than 3 years.
• Depressive symptom severity as demonstrated by CDRS-R total composite score of forty or greater and a suicidal ideation score of 3 or more on item 13 of the CDRS-R.
• A minimum score of 1 ("wish to be dead") on the C-SSRS severity of ideation subscale.
• Demonstrating that depressive symptom severity as evaluated at the screening visit does not improve between screening and baseline by 25% or more.
• Eligible for transcranial magnetic stimulation (TMS) based on safety criteria.
• On a medically acceptable form of birth control if female and of child bearing potential.
• Taking an antidepressant medication if recommended by the referring clinician and agreed upon by parents and patients. Please note that patients are not required to take an antidepressant medication for study participation for practical, ethical, and human subject protection concerns. Medication status and prior treatment resistance will be carefully recorded with the Antidepressant Treatment History Form criteria for relevant statistical considerations.

Exclusion Criteria:

• Diagnosis of a psychotic disorder, bipolar disorder, anorexia nervosa, bulimia nervosa, substance use disorders within the past year (with the exception of caffeine and tobacco).
• Intelligent quotient less than 70 (if there is a clinical concern, subjects will be psychometrically assessed with the Slosson Intelligence Test, Revised).
• Positive urine drug screen at baseline.
• Patients with a history of epilepsy or unexplained seizures.
• Any family history of epilepsy.
• Patients medicated with drugs lowering the seizure threshold (examples: neuroleptic agents and tricyclic antidepressants).
• History of any treatment with electroconvulsive therapy or TMS.
• Use of any investigational drug within 4 weeks of baseline.
• Prior brain surgery.
• Risk for increased intracranial pressure such as a brain tumor.
• Head trauma with loss of consciousness.
• Any true positive findings on the TMS safety screening form.
• Pregnant or nursing patients.
• Conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head within. 30 cm of the treatment coil excluding the mouth that cannot be safely removed (examples include cochlear implants, vagus nerve stimulators (VNS), deep brain stimulators, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes).
• Patients with any implanted stimulators or implants controlled by physiologic signals, including vagus nerve stimulators, spinal cord stimulators, peripheral nerve stimulators, defibrillators and pacemakers.
• Patients with neurological conditions that include a history of seizures, cerebrovascular disease, cerebral aneurysm, dementia, movement disorders, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system.
• Patients with a history of increased intracranial pressure or history of severe headaches within the previous 1 year.
• Implanted medication pumps and cardiac pacemakers.
• Patients suffering from vascular, traumatic, tumoral, infectious, or metabolic lesions of the brain, even without a history of seizure, or without anticonvulsant medication.
• Patients with a history of increased intracranial pressure or severe head trauma.
• Patients with an unstable medical illness (other than depression).
• Inability to adhere to the protocol.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Suicidal Ideation

Intervention

Device:
• MagVenture TMS Therapy System w/Theta Burst Stimulation
The device consists of a magnetic stimulator, MagPro X100 (K173620), and a magnetic coil used for motor threshold determination, C-B70, and a treatment coil, the Cool-B70 A/P coil, to deliver sequential bilateral accelerated theta burst stimulation. The Cool-B70 A/P coil is a coil designed specifically for use in double-blind, sham-controlled trials. The A/P version of the coil, contains both an active site (A) and a sham (P) site. The magnetic field on the sham site is significantly reduced, and is less than 5% of that of the active site.
• Sham MagVenture TMS Therapy System w/Theta Burst Stimulation
The device consists of a magnetic stimulator, MagPro X100 (K173620), and a magnetic coil used for motor threshold determination, C-B70, and a treatment coil, the Cool-B70 A/P coil, to deliver sequential bilateral accelerated theta burst stimulation. The Cool-B70 A/P coil is a coil designed specifically for use in double-blind, sham-controlled trials. The A/P version of the coil, contains both an active site (A) and a sham (P) site. The magnetic field on the sham site is significantly reduced, and is less than 5% of that of the active site.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Paul E. Croarkin	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Suicidal Ideation	Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) severity of ideation subscale over the 10-day sequential bilateral accelerated Theta Burst Stimulation (aTBS) trial period	Baseline, daily over 10 days (during intervention), and monthly for 12 months
Primary	Change in Number of Hospitalizations	Number of hospitalizations related to suicidal ideation	12 month follow-up period (assessed monthly)
Primary	Change in Number of Emergency Department Visits	Number of emergency department visits related to suicidal ideation	12 month follow-up period (assessed montly)

External Links

•   Mayo Clinic Clinical Trials