Treatment of Acute Mood Depressive Episode in Borderline Personality Disorder With rTMS

Study Overview
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Brief Summary
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This study evaluates the antidepressant effects of an accelerated schedule of theta-burst stimulation, termed accelerated intermittent theta-burst stimulation (aiTBS), in individuals with borderline personality disorder (BPD) or trait and comorbid mood depressive disorder (MDD) or bipolar II disorder in a current mood depressive episode (MDE).

Detailed Description
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This project aims to measure and modulate a mood depressive episode (MDE) in individuals with borderline personality disorder (BPD) trait and comorbid mood depressive disorder (MDD) or bipolar II disorder in a current mood depressive episode (MDE). This study will test the antidepressant effect of aiTBS stimulation over the left dorsolateral prefrontal cortex (L-DLPFC), and aiTBS stimulation over the dorsomedial prefrontal cortex (DMPFC) compared with sham.

Official Title
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Modulating Probabilities: Prediction, Assessment, and Treatment of Acute Mood Depressive Episode in Borderline Personality Disorder With rTMS

Conditions
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Depressive Disorder, Major, Borderline Personality Disorder

Intervention / Treatment
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* Device: Left Dorsolateral Prefrontal Cortex (L-DLPFC)
* Device: Dorsomedial Prefrontal Cortex (DMPFC)
* Device: Sham Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, between the ages of 22 and 65 at the time of screening. Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with 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. Diagnosed with Major Depressive Disorder (MDD) or Bipolar II, or unspecified depressive disorder AND Borderline Personality Disorder or trait, with a current Mood Depressive Episode (MDE), according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5). MADRS score of ≥20 at screening (Visit 1). TMS naive. Access to ongoing psychiatric care before and after completion of the study. Access to clinical rTMS after study completion. In good general health, as evidenced by medical history. 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. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration. Exclusion Criteria: Pregnancy The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation) Current mania or psychosis Bipolar I Disorder and primary psychotic disorders. Autism Spectrum disorder or Intellectual Disability A diagnosis of obsessive-compulsive disorder (OCD) Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal. Urine screening test positive for illicit substances. Any history of ECT (greater than 8 sessions) without meeting responder criteria Recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT). History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma. Untreated or insufficiently treated endocrine disorder. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) Contraindications to MRI (ferromagnetic metal in their body). 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. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO) 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.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to receive: active L-DLPFC stimulation, active DMPFC stimulation, or sham stimulation. Group size ratio will be 1:1:1.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Left Dorsolateral Prefrontal Cortex (L-DLPFC)<br>The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (L-DLPFC) | Device: Left Dorsolateral Prefrontal Cortex (L-DLPFC)<br>* Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system.<br>|
| Active Comparator: Dorsomedial Prefrontal Cortex (DMPFC)<br>The accelerated theta burst stimulation protocol will be applied to the dorsomedial prefrontal cortex (DMPFC) | Device: Dorsomedial Prefrontal Cortex (DMPFC)<br>* Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) to the DMPFC. Stimulation intensity will be standardized at 100% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system.<br>|
| Sham Comparator: Sham stimulation<br>Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region | Device: Sham Stimulation<br>* Participants who are randomly assigned to this group will receive sham stimulation to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the clinician rated Montgomery-Asberg Depression Rating Scale (MADRS-C) in active L-DLPFC vs. sham aiTBS. | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.The MADRS-C has an overall score range from 0-60, with higher scores corresponding to higher levels of depression. | At baseline (pre-intervention), during the intervention and immediately after the intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the clinician rated Montgomery-Asberg Depression Rating Scale (MADRS-C) in active DMPFC vs. sham aiTBS. | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.The MADRS-C has an overall score range from 0-60, with higher scores corresponding to higher levels of depression. | At baseline (pre-intervention), during the intervention and immediately after the intervention. | 
| Feasibility of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by retention rates | Retention rates will be determined as research follow-up rate ≥80% | At baseline (pre-intervention), during the intervention and immediately after the intervention. | 
| Feasibility of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by recruitment rate | Recruitment rate will be determined by actual recruitment/recruitment milestones | At baseline (pre-intervention), during the intervention and immediately after the intervention. | 
| Safety of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by rate of suicidal behaviors | Rate of suicidal behaviors will be determined by number of participants that committed a SB/total number of participants | At baseline (pre-intervention), during the intervention and immediately after the intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Neuromodulation, Transcranial Magnetic Stimulation, Borderline Personality Disorder