Pilot Accelerated Theta Burst in Treatment-Resistant Bipolar Depression

Study Overview
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Brief Summary
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This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant bipolar depression. In this open-label study, all participants will receive accelerated theta-burst stimulation.

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real-world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session over 4-6 weeks). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. In a recent study, the investigators applied this accelerated paradigm in individuals with treatment-resistant depression (TRD), which showed a significant antidepressant effect (90% remission rate). Additionally, 3 participants from this study carried a bipolar TRD diagnosis and responded at minimum, equally as well, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. This study intends to further modify the parameters to create a more rapid form of this treatment for bipolar TRD, and look at the change in clinical measures and neuroimaging biomarkers.

Official Title
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Pilot Accelerated Theta Burst Stimulation in Treatment-Resistant Bipolar Depression

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Device: Accelerated intermittent theta-burst treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 80 years of age. Able to provide informed consent. Diagnosed with Bipolar Disorder and currently experiencing a Major Depressive Episode (MDE). Meet the threshold on the total MADRS score of >/=20 at baseline. In good general health, as ascertained by medical history. If female, a status of non-childbearing potential or use of an acceptable form of birth control. History of rTMS failure with FDA approved rTMS parameters is permitted. Exclusion Criteria: Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. Female that is pregnant or breastfeeding. Female with a positive pregnancy test at participation. Total MADRS score of < 20 at study entry. Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence. Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more). History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their bipolar depression or has been predominant to their bipolar depression at any time within six months prior to screening. Considered at significant risk for suicide during the course of the study. Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. 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. History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. Current (or chronic) use of opiates. History of epilepsy. History of shrapnel or metal in the head or skull. History of cardiovascular disease or cardiac event. History of OCD. History of autism spectrum disorder. Current psychosis Any change in medication of which the study PI is not aware of.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated intermittent theta burst treatment<br>All participants will receive accelerated intermittent theta-burst stimulation. | Device: Accelerated intermittent theta-burst treatment<br>* All participants will receive accelerated intermittent theta-burst stimulation to the left DLPFC. Treatment will be targeted by utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance. Stimulation will be delivered to left DLPFC using the MagPRo stimulator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and immediately post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and immediate post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Disorder, Treatment Resistant Depression, Transcranial Magnetic Stimulation (TMS), Theta Burst