Clinical trial NCT04870255: Treatment of Acute Mood Depressive Episode in Borderline Personality Disorder with RTMS
Official title: Modulating Probabilities: Prediction, Assessment, and Treatment of Acute Mood Depressive Episode in Borderline Personality Disorder with RTMS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depressive Disorder, Major
Borderline Personality Disorder
Keywords: Depression
Neuromodulation
Transcranial Magnetic Stimulation
Borderline Personality Disorder
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2021-05-03
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Male or Female, between the ages of 18 and 80 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.

Primary outcomes:
measure: Change in the clinician rated Montgomery-Asberg Depression Rating Scale (MADRS-C) in active L-DLPFC vs. sham aiTBS.
timeFrame: At baseline (pre-intervention), during the intervention and immediately after the intervention.
Secondary outcomes:
measure: Change in the clinician rated Montgomery-Asberg Depression Rating Scale (MADRS-C) in active DMPFC vs. sham aiTBS.
timeFrame: At baseline (pre-intervention), during the intervention and immediately after the intervention.
measure: Feasibility of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by retention rates
timeFrame: At baseline (pre-intervention), during the intervention and immediately after the intervention.
measure: Feasibility of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by recruitment rate
timeFrame: At baseline (pre-intervention), during the intervention and immediately after the intervention.
measure: Safety of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by rate of suicidal behaviors
timeFrame: At baseline (pre-intervention), during the intervention and immediately after the intervention.
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital
state: California
Study officials:
affiliation: Stanford University
name: Nolan Williams, MD
role: STUDY_DIRECTOR
affiliation: Stanford University
name: David Spiegel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
citation: George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
citation: Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
citation: Abdallah CG, Averill LA, Collins KA, Geha P, Schwartz J, Averill C, DeWilde KE, Wong E, Anticevic A, Tang CY, Iosifescu DV, Charney DS, Murrough JW. Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology. 2017 May;42(6):1210-1219. doi: 10.1038/npp.2016.186. Epub 2016 Sep 8.
citation: Liston C, Chen AC, Zebley BD, Drysdale AT, Gordon R, Leuchter B, Voss HU, Casey BJ, Etkin A, Dubin MJ. Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry. 2014 Oct 1;76(7):517-26. doi: 10.1016/j.biopsych.2014.01.023. Epub 2014 Feb 5.
citation: Green KL, Brown GK, Jager-Hyman S, Cha J, Steer RA, Beck AT. The Predictive Validity of the Beck Depression Inventory Suicide Item. J Clin Psychiatry. 2015 Dec;76(12):1683-6. doi: 10.4088/JCP.14m09391.
citation: Ballard ED, Reed JL, Szczepanik J, Evans JW, Yarrington JS, Dickstein DP, Nock MK, Nugent AC, Zarate CA Jr. Functional Imaging of the Implicit Association of the Self With Life and Death. Suicide Life Threat Behav. 2019 Dec;49(6):1600-1608. doi: 10.1111/sltb.12543. Epub 2019 Feb 13.
citation: Tello N, Harika-Germaneau G, Serra W, Jaafari N, Chatard A. Forecasting a Fatal Decision: Direct Replication of the Predictive Validity of the Suicide-Implicit Association Test. Psychol Sci. 2020 Jan;31(1):65-74. doi: 10.1177/0956797619893062. Epub 2019 Dec 11.
citation: Light SN, Bieliauskas LA, Taylor SF. Measuring change in anhedonia using the "Happy Faces" task pre- to post-repetitive transcranial magnetic stimulation (rTMS) treatment to left dorsolateral prefrontal cortex in Major Depressive Disorder (MDD): relation to empathic happiness. Transl Psychiatry. 2019 Sep 3;9(1):217. doi: 10.1038/s41398-019-0549-8.
citation: Baeken C, Duprat R, Wu GR, De Raedt R, van Heeringen K. Subgenual Anterior Cingulate-Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment? Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Oct;2(7):556-565. doi: 10.1016/j.bpsc.2017.01.001. Epub 2017 Jan 20.
citation: Downar J, Geraci J, Salomons TV, Dunlop K, Wheeler S, McAndrews MP, Bakker N, Blumberger DM, Daskalakis ZJ, Kennedy SH, Flint AJ, Giacobbe P. Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression. Biol Psychiatry. 2014 Aug 1;76(3):176-85. doi: 10.1016/j.biopsych.2013.10.026. Epub 2013 Nov 28.
citation: Duprat R, De Raedt R, Wu GR, Baeken C. Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity. Front Hum Neurosci. 2016 Jun 16;10:294. doi: 10.3389/fnhum.2016.00294. eCollection 2016.
citation: Schmaal L, van Harmelen AL, Chatzi V, Lippard ETC, Toenders YJ, Averill LA, Mazure CM, Blumberg HP. Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies. Mol Psychiatry. 2020 Feb;25(2):408-427. doi: 10.1038/s41380-019-0587-x. Epub 2019 Dec 2.
citation: Gartner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Boker H, Hattenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.