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

Primary Purpose

Bipolar II Disorder, Most Recent Episode Major Depressive, Current Depressive Episode, Treatment Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active Comparator: Active aiTBS
Sham Comparator: Sham aiTBS
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar II Disorder, Most Recent Episode Major Depressive focused on measuring Bipolar II Disorder, Treatment Resistant Depression, Transcranial Magnetic Stimulation (TMS), Theta Burst

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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). 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. Meet the criteria by Maudsley Staging Method score >=7 Not in a current state of hypomania (as assessed by the Young Mania Rating Scale) or psychosis In good general health, as ascertained by medical history. Must have a stable psychiatrist during study enrollment, who confirms diagnosis of bipolar II disorder. Must be on a mood stabilizer regimen for 6 weeks prior to study enrollment and agree to continue this regimen during study period Meet the threshold on the MADRS, with a total score of >/=20 at screening/baseline. 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: Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9). 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. 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: Primary diagnosis other than bipolar II disorder 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. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants History of epilepsy or seizures Shrapnel or any ferromagnetic item in the head Pregnancy Autism Spectrum disorder 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 Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines Cognitive impairment (including dementia) Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation) Current hypomania or psychosis Showing symptoms of withdrawal from alcohol or benzodiazepines A diagnosis of intellectual disability Parkinsonism or other movement disorder determined by Principal Investigator to interfere with treatment Any other indication the Principal Investigator feels would comprise data. Current active suicidal ideation or suicide attempt or suicidal behaviors in the last 6 months Any history of psycho surgery for depression Any history of ECT (greater than 8 sessions) without meeting responder criteria 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

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Active aiTBS

Sham aiTBS

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change from baseline Montgomery Asberg Depression Rating Scale (MADRS)
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.

Secondary Outcome Measures

Change from baseline Young Mania Rating Scale (YMRS)
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).
Change in resting-state functional connectivity
Resting-state fMRI scans will be conducted before and after the course of aiTBS to examine changes in resting-state functional connectivity.

Full Information

First Posted
April 28, 2023
Last Updated
May 6, 2023
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT05849402
Brief Title
Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder
Official Title
Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 20, 2022 (Actual)
Primary Completion Date
July 1, 2026 (Anticipated)
Study Completion Date
July 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar II Disorder, Most Recent Episode Major Depressive, Current Depressive Episode, Treatment Resistant Depression
Keywords
Bipolar II Disorder, Treatment Resistant Depression, Transcranial Magnetic Stimulation (TMS), Theta Burst

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active aiTBS
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Sham aiTBS
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active Comparator: Active aiTBS
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham Comparator: Sham aiTBS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from baseline Montgomery Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
Baseline and immediately post-treatment, 1-month
Secondary Outcome Measure Information:
Title
Change from baseline Young Mania Rating Scale (YMRS)
Description
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).
Time Frame
Baseline and immediate post-treatment, 1-month
Title
Change in resting-state functional connectivity
Description
Resting-state fMRI scans will be conducted before and after the course of aiTBS to examine changes in resting-state functional connectivity.
Time Frame
After all stimulation sessions have been completed (approximately 48 hours after the final session)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). 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. Meet the criteria by Maudsley Staging Method score >=7 Not in a current state of hypomania (as assessed by the Young Mania Rating Scale) or psychosis In good general health, as ascertained by medical history. Must have a stable psychiatrist during study enrollment, who confirms diagnosis of bipolar II disorder. Must be on a mood stabilizer regimen for 6 weeks prior to study enrollment and agree to continue this regimen during study period Meet the threshold on the MADRS, with a total score of >/=20 at screening/baseline. 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: Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9). 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. 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: Primary diagnosis other than bipolar II disorder 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. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants History of epilepsy or seizures Shrapnel or any ferromagnetic item in the head Pregnancy Autism Spectrum disorder 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 Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines Cognitive impairment (including dementia) Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation) Current hypomania or psychosis Showing symptoms of withdrawal from alcohol or benzodiazepines A diagnosis of intellectual disability Parkinsonism or other movement disorder determined by Principal Investigator to interfere with treatment Any other indication the Principal Investigator feels would comprise data. Current active suicidal ideation or suicide attempt or suicidal behaviors in the last 6 months Any history of psycho surgery for depression Any history of ECT (greater than 8 sessions) without meeting responder criteria 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nick Bassano, MSW
Phone
650-800-6929
Email
nbassano@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Ian Kratter, MD, PhD
Email
ikratter@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian Kratter, MD, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ian Kratter, MD, PhD
Email
ikratter@stanford.edu

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
www.clinicaltrials.gov
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Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder

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