iTBS in Bipolar I Depression

A Pilot Study of iTBS in Bipolar I Depression

A multisite, open label pilot study to investigate the efficacy and safety of a novel accelerated intermittent theta-burst stimulation (iTBS) protocol while assessing for changes in neuroimaging biomarkers associated with treatment response.

Study Overview

• Status: Completed
• Conditions: Bipolar Depression; Bipolar I Disorder
• Intervention / Treatment: Device: Magnus Transcranial Magnetic Neuromodulation System (MNS) with SAINT®(Stanford Accelerated Intelligent Neuromodulation Therapy)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21217
      • Johns Hopkins
  • Texas
    • Austin, Texas, United States, 78712
      • University of Texas at Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 22-65 years of age
2. Bipolar I disorder diagnosis as defined by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
3. Currently experiencing a Major Depressive Episode with Montgomery-Asberg Depression Rating Scale (MADRS) >/= 20 at screening [Day -5/-14] and baseline [Day 0]
4. On a stable and adequate dose of an anti-manic agent (Lithium with a level of at least 0.6, Depakote with a level of at least 50, or a therapeutic dose of carbamazepine, oxcarbazepine, or a neuroleptic for treatment of mania per clinician judgment) without dose changes for at least 6 weeks prior to the active study time period. Final assessment of appropriateness of participant's pharmacologic regimen is subject to study team clinician judgment.
5. Having failed a therapeutic trial of a first line bipolar depression antidepressant (as specified by the Antidepressant Treatment History Form and updated with new medications approved by the FDA for treatment of bipolar depression) in this current episode. This includes a minimum 4 week trial of one of the following medications (minimum dosage): lithium 900mg daily (or blood level >= 0.6 milliequivalent/Liter (mEq/L), carbamazepine 400mg daily (or blood level >= 0.8 mEq/L), lamotrigine 200mg daily, asenapine 20mg daily, lurasidone 20mg daily, olanzapine 10mg daily, quetiapine 300mg daily, or lumateperone 42mg daily. Final determination of a failed adequate therapeutic trial is subject to study team clinician judgement.
6. Established outpatient psychiatrist

Exclusion Criteria:

1. Female that is pregnant or breastfeeding, or of childbearing potential but not using medically acceptable birth control during study
2. Current mixed episode assessed by clinician judgment as defined by DSM-5 criteria
3. Current active substance use disorder (as defined by DSM-5) with exception of nicotine and caffeine. Participants may be subject to urine drug screen base on study team clinician judgment.
4. Participation in any clinical trial with an investigational drug or device within the last 3 month or concurrent to study participation
5. History of epilepsy, shrapnel or metal in the head or skull, cardiovascular disease/event, Obsessive Compulsive Disorder, or autism spectrum disorder
6. Clinically defined major neurological disorder; including, but not limited to, seizure disorder and history of loss of consciousness due to head injury for greater than 10 minutes, or documented evidence of brain injury
7. Active suicidal risk based on investigator's clinical judgment
8. Clinically significant unstable medical condition
9. Other condition judged by investigator that could prevent the participant from completion of the study (such as but not limited to, significant physical disability (e.g., hearing/visual deficits) to perform a neutral memory task and/or neuropsychological test battery)
10. Ferromagnetic metal implant or another contraindication to imaging in a 3 Tesla MRI
11. Electroconvulsive therapy (ECT) treatment in the past 3 months
12. Minimum of 6 months since last manic or hypomanic episode as defined by DSM-5 criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment Arm; Open label study, all participants will receive novel iTBS	Device: Magnus Transcranial Magnetic Neuromodulation System (MNS) with SAINT®(Stanford Accelerated Intelligent Neuromodulation Therapy); Novel intermittent theta burst stimulation protocol with individualized targets in the brain for stimulation using structural and functional MRI inputs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score	The MADRS is a ten-item clinician rated questionnaire that helps rate the severity of depression. Total scores can range from 0 to 60, with higher scores indicating greater severity of depression (0-6 normal range, 7-19 mild depression, 20-34 moderate depression, >34 severe depression). MADRS score will be assessed at baseline visit and immediate follow-up visit (which occurs within 5 days after treatment end). The change in MADRS score is calculated by baseline - immediate follow-up visit score.	baseline and post treatment up to 5 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: University of Texas at Austin; Baszucki Brain Research Fund; Magnus Medical
• Investigators: Principal Investigator: Peter Zandi, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7.
• Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): November 22, 2023

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder
• Other Study ID Numbers: IRB00327675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No