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Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder

Primary Purpose

Bipolar Disorder, Manic, Bipolar Disorder I

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Accelerated intermittent theta-burst stimulation over right DLPFC
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder, Manic

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participants aged 18yo-80yo with a primary diagnosis of bipolar I or II disorder in a current hypomanic/manic episode or bipolar affective disorder II in a current hypomanic/manic episode.
  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. Currently experiencing a hypomanic/manic episode according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
  4. Meet the threshold on the total HAMD17 score of >/=20 prior to aiTBS.
  5. Meet the threshold on the BDI-II score of >/=17 prior to aiTBS.
  6. Not currently experiencing psychosis (MINI)

8. Must have a stable psychiatrist during study enrollment

9. Must be on a mood stabilizer regimen

12. Meet the threshold on the MADRS, with a total score of >/=20 prior to aiTBS.

13. History of ECT intolerance or exposure is permitted.

Exclusion Criteria:

  1. 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.
  2. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants
  3. History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)
  4. Shrapnel or any ferromagnetic item in the head
  5. Pregnancy
  6. Autism Spectrum disorder
  7. 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
  8. Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
  9. Cognitive impairment (including dementia)
  10. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
  11. Current psychosis
  12. Showing symptoms of withdrawal from alcohol or benzodiazepines
  13. IQ<70
  14. Parkinsonism or other movement d/o determined by PI to interfere with treatment
  15. Any other indication the PI feels would comprise data.
  16. A diagnosis of obsessive-compulsive disorder (OCD)
  17. Any history of psycho surgery for depression
  18. Any history of myocardial infarction, CABG, CHF, or other cardiac history
  19. The presence or diagnosis of prominent anxiety disorder, personality disorder or dysthymia
  20. History of intractable migraine

Sites / Locations

  • Stanford Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Right DLPFC aiTBS stimulation

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events

Secondary Outcome Measures

Young Mania Rating Scale [YMRS] Score
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms.

Full Information

First Posted
August 5, 2019
Last Updated
June 23, 2023
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT04058249
Brief Title
Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder
Official Title
Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Difficulty with recruitment
Study Start Date
November 1, 2019 (Actual)
Primary Completion Date
December 20, 2021 (Actual)
Study Completion Date
December 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder, Manic, Bipolar Disorder I

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Right DLPFC aiTBS stimulation
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
Accelerated intermittent theta-burst stimulation over right DLPFC
Intervention Description
All participants will receive accelerated intermittent theta-burst stimulation to the right DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance. Stimulation will be delivered to right-DLPFC using the Brainsway stimulator.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events
Time Frame
6 days
Secondary Outcome Measure Information:
Title
Young Mania Rating Scale [YMRS] Score
Description
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms.
Time Frame
Baseline, day 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Marie Batail, MD, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder

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