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

Sponsor
Stanford University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05849402
Collaborator
(none)
60
Enrollment
1
Location
2
Arms
43.3
Anticipated Duration (Months)
1.4
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Active Comparator: Active aiTBS
  • Device: Sham Comparator: Sham aiTBS
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder
Actual Study Start Date :
Dec 20, 2022
Anticipated Primary Completion Date :
Jul 1, 2026
Anticipated Study Completion Date :
Jul 30, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

  1. Change from baseline Young Mania Rating Scale (YMRS) [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).

  2. Change in resting-state functional connectivity [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  10. 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.

  11. 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)

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

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

  23. History of intractable migraine

  24. Hypomania in the past 6 months.

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

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

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Stanford University Palo Alto California United States 94305

Sponsors and Collaborators

  • Stanford University

Investigators

  • Principal Investigator: Ian Kratter, MD, PhD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ian Kratter, Clinical Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford University
ClinicalTrials.gov Identifier:
NCT05849402
Other Study ID Numbers:
  • 49486-RCT
First Posted:
May 8, 2023
Last Update Posted:
May 8, 2023
Last Verified:
Apr 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Keywords provided by Ian Kratter, Clinical Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford University
Bipolar II Disorder
Treatment Resistant Depression
Transcranial Magnetic Stimulation (TMS)
Theta Burst
Additional relevant MeSH terms:
Disease
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant

Study Results

No Results Posted as of May 8, 2023