Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder

This study evaluates the efficacy of an accelerated schedule of theta-burst stimulation for treating manic episodes in bipolar disorder. In this open-label study, all participants will receive accelerated theta-burst stimulation.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder I; Bipolar Disorder, Manic
• Intervention / Treatment: Device: Accelerated intermittent theta-burst stimulation over right DLPFC

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real-world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session over 4-6 weeks). Recently, researchers have modified the treatment parameters to reduce treatment times with some preliminary success. In a recent study, an accelerated paradigm showed a significant antidepressant effect (90% remission rate) in individuals with treatment-resistant depression (TRD), in only 5 days. Additionally, 5 participants from this study carried a bipolar diagnosis and responded similarly, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. In parallel to this, evidence in the literature shows that right prefrontal rapid TMS is safe and efficacious in the treatment of bipolar mania showing laterality opposed to the proposed effect of rapid TMS in depression.

The current trial intends to utilise this modified design, i.e., an accelerated theta burst stimulation treatment over the right prefrontal cortex, for manic episodes in bipolar disorder. The trial also aims to look at the change in clinical measures and neuroimaging biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, between the ages of 18 and 80 years at the time of screening.
• Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questions and follow instructions during fMRI assessments and aiTBS interventions
• Stated willingness to adhere to all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information
• Primary diagnosis of Bipolar I or II Disorder according to the Diagnosis and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
• Currently experiencing a hypomanic or manic episode according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
• YMRS score of ≥12 at screening.
• Access to ongoing psychiatric care after completion of the study.
• Must be adherent or agreeable to pharmacotherapy per clinical standard of care at screening.
• Patients who are in both voluntary and involuntary hold.
• In good general health, as evidenced by medical history.
• For females of reproductive potential: use of highly effective contraception.

Exclusion Criteria:

• Currently pregnant or breastfeeding.
• Primary psychiatric condition other than Bipolar I or II Disorder requiring treatment other than stable comorbid anxiety disorder.
• Diagnosis of Intellectual Disability or Autism Spectrum Disorder
• Current moderate or severe substance use disorder or demonstrating signs of acute substance intoxication or withdrawal
• Active suicidal ideation (defined as an M-SSI > 8)
• History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
• Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
• Contraindication to MRI (e.g. ferromagnetic metal in their body)
• Treatment with another investigational drug or other intervention within the study period
• Any other condition deemed by the PI to interfere with the study or increase risk to the participant
• Current unmanageable psychosis that the PI believes would interfere with treatment
• Any history of psychosurgery
• Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO).
• Any other condition deemed by the PI to interfere with the study or increase risk to the participant.

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
Experimental: Right DLPFC aiTBS stimulation	Device: Accelerated intermittent theta-burst stimulation over right DLPFC; All participants will receive accelerated intermittent theta-burst stimulation to the right DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance. Stimulation will be delivered to right-DLPFC using the Brainsway stimulator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment Emergent Adverse Events	6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Young Mania Rating Scale [YMRS] Score	The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms.	Baseline, day 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting-state recordings and TMS-evoked potentials in EEG data.	EEG recordings will be made before and after the treatment course to differences in EEG data associated with hypomania/mania and treatment response (e.g. amplitude & latency of tms-evoked potentials (TEPs), spatio-temporal distribution of TEPs and resting-state connectivity)	Baseline and immediate post-treatment
Change in heart rate variability	Polar H10 heart rate monitor will be used to measure heart rate variability	Baseline and immediate post-treatment

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Jean-Marie Batail, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): December 20, 2021

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: June 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: 52635 (Patrick and Catherine Weldon Donaghue Foundation)

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