Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder

April 26, 2024 updated by: Bora Kim, Stanford University
The purpose of this study is to investigate the effectiveness of accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) in inducing anti-depressant responses in individuals with treatment-resistant depression of bipolar II disorder. This is a double-blind, randomized, sham-controlled trial that targets a single location on the left dorsolateral prefrontal cortex (LDLPFC) using the MagPro rTMS system.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The aim of this study is to assess the efficacy of aiTBS applied to the left dorsolateral prefrontal cortex (L-DLPFC) in reducing depressive symptoms in individuals with bipolar II disorder, and to determine the neural functional connectivity changes that underlie treatment response. A total of 60 individuals with bipolar II disorder who are currently experiencing a depressive episode will be recruited for the study.

The accelerated iTBS (aiTBS) treatment will consist of 10 sessions, administered daily over a period of 5 consecutive days. Before and after the stimulation, magnetic resonance imaging (MRI) scans, electroencephalograms (EEG), and heart rate variability (HRV) will be collected. The severity of depressive symptoms will be evaluated using both clinician-rated and self-report assessments.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participants aged 18 years old to 80 years old with a primary diagnosis of bipolar affective disorder II in a current major depressive episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Fourth Edition, Text Revision (DSM-V).
  2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
  3. Meet the criteria by Maudsley Staging Method score >=7
  4. Not in a current state of hypomania (as assessed by the Young Mania Rating Scale) or psychosis
  5. In good general health, as ascertained by medical history.
  6. Must have a stable psychiatrist during study enrollment, who confirms diagnosis of bipolar II disorder.
  7. Must be on a mood stabilizer regimen for 6 weeks prior to study enrollment and agree to continue this regimen during study period
  8. Meet the threshold on the MADRS, with a total score of >/=20 at screening/baseline.
  9. TMS Naive

11. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

12. Agreement to adhere to Lifestyle Considerations throughout study duration.

Lifestyle considerations:

  1. Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9).
  2. Continue usual intake patterns of caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) without significant change for the duration of the study.
  3. Abstain from alcohol for at least 24 hours before the start of each MRI and TMS session.

Participants who use tobacco products will be informed that use will be allowed only in between intervention sessions.

Exclusion Criteria:

  1. Primary diagnosis other than bipolar II disorder
  2. Any structural lesion e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke effecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
  3. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants
  4. History of epilepsy or seizures
  5. Shrapnel or any ferromagnetic item in the head
  6. Pregnancy
  7. Autism Spectrum disorder
  8. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation
  9. Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
  10. Cognitive impairment (including dementia)
  11. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
  12. Current hypomania or psychosis
  13. Showing symptoms of withdrawal from alcohol or benzodiazepines
  14. A diagnosis of intellectual disability
  15. Parkinsonism or other movement disorder determined by Principal Investigator to interfere with treatment
  16. Any other indication the Principal Investigator feels would comprise data.
  17. Current active suicidal ideation or suicide attempt or suicidal behaviors in the last 6 months
  18. Any history of psycho surgery for depression
  19. Any history of ECT (greater than 8 sessions) without meeting responder criteria
  20. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT)

22. Any history of myocardial infarction, CABG, CHF, or other cardiac history

23. The presence or diagnosis of prominent anxiety disorder, personality disorder or dysthymia

24. History of intractable migraine

25. Hypomania in the past 6 months.

26. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)

27. Unstable symptoms between screening and baseline as defined by a 30% change in MADRS-C score.

28. Any other condition deemed by the PI to interfere with the study or increase risk to the participant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active aiTBS
Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.
Device: Active Comparator: Active aiTBS
Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.
Sham Comparator: Sham aiTBS
Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.
Device: Sham Comparator: Sham aiTBS
Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline Montgomery Asberg Depression Rating Scale (MADRS)
Time Frame: Baseline and immediately post-treatment, 1-month

A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.

The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.
Baseline and immediately post-treatment, 1-month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline Young Mania Rating Scale (YMRS)
Time Frame: Baseline and immediate post-treatment, 1-month

The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition.

There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients.

Typical YMRS baseline scores can vary a lot. They depend on the patients' clinical features such as mania (YMRS = 12), depression (YMRS = 3), or euthymia (YMRS = 2).
Baseline and immediate post-treatment, 1-month
Change in resting-state functional connectivity
Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
Resting-state fMRI scans will be conducted before and after the course of aiTBS to examine changes in resting-state functional connectivity.
After all stimulation sessions have been completed (approximately 48 hours after the final session)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Nolan Williams, MD, Stanford University
  • Study Director: Bora Kim, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2022

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 30, 2026

Study Registration Dates

First Submitted

April 28, 2023

First Submitted That Met QC Criteria

May 6, 2023

First Posted (Actual)

May 8, 2023

Study Record Updates

Last Update Posted (Actual)

April 30, 2024

Last Update Submitted That Met QC Criteria

April 26, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 49486-RCT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

www.clinicaltrials.gov

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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