Clinical trial NCT04058249: Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder
Official title: Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Bipolar Disorder, Manic
Bipolar Disorder I
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2019-08-15
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the efficacy of an accelerated schedule of theta-burst stimulation for treating manic episodes in bipolar disorder. In this open-label study, all participants will receive accelerated theta-burst stimulation.

Detailed description: 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 modified the treatment parameters to reduce treatment times with some preliminary success. In a recent study, an accelerated paradigm showed a significant antidepressant effect (90% remission rate) in individuals with treatment-resistant depression (TRD), in only 5 days. Additionally, 5 participants from this study carried a bipolar diagnosis and responded similarly, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. In parallel to this, evidence in the literature shows that right prefrontal rapid TMS is safe and efficacious in the treatment of bipolar mania showing laterality opposed to the proposed effect of rapid TMS in depression.

The current trial intends to utilise this modified design, i.e., an accelerated theta burst stimulation treatment over the right prefrontal cortex, for manic episodes in bipolar disorder. The trial also aims to look at the change in clinical measures and neuroimaging biomarkers.

Eligibility criteria: Inclusion Criteria:

* Male or female, between the ages of 18 and 80 years at the time of screening.
* Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questions and follow instructions during fMRI assessments and aiTBS interventions
* Stated willingness to adhere to 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
* Primary diagnosis of Bipolar I or II Disorder according to the Diagnosis and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
* Currently experiencing a hypomanic or manic episode according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
* YMRS score of ≥12 at screening.
* Access to ongoing psychiatric care after completion of the study.
* Must be adherent or agreeable to pharmacotherapy per clinical standard of care at screening.
* Patients who are in both voluntary and involuntary hold.
* In good general health, as evidenced by medical history.
* For females of reproductive potential: use of highly effective contraception.

Exclusion Criteria:

* Currently pregnant or breastfeeding.
* Primary psychiatric condition other than Bipolar I or II Disorder requiring treatment other than stable comorbid anxiety disorder.
* Diagnosis of Intellectual Disability or Autism Spectrum Disorder
* Current moderate or severe substance use disorder or demonstrating signs of acute substance intoxication or withdrawal
* Active suicidal ideation (defined as an M-SSI \> 8)
* History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
* Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
* Contraindication to MRI (e.g. ferromagnetic metal in their body)
* 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
* Current unmanageable psychosis that the PI believes would interfere with treatment
* Any history of psychosurgery
* Depth-adjusted aiTBS treatment dose \> 65% maximum stimulator output (MSO).
* Any other condition deemed by the PI to interfere with the study or increase risk to the participant.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: 6 days
Secondary outcomes:
measure: Young Mania Rating Scale [YMRS] Score
timeFrame: Baseline, day 6
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Hospital
state: California
Study officials:
affiliation: Stanford University
name: Jean-Marie Batail, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: