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Bipolar Efficacy Biomarkers for rTMS

Primary Purpose

Bipolar Disorder, Bipolar Depression

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Accelerated Theta Burst Stimulation
Sham accelerated Theta Burst Stimulation
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring theta burst stimulation, accelerated TBS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Bipolar depression (BP I and BP II) by DSM 5 criteria (Diagnostic and Statistical Manual of Mental Disorders, 2013)
  • Age 18-70
  • Right or left handed
  • All genders
  • Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria (Sackeim et al., 2019)
  • Able to provide informed consent to participate in the study
  • Must be on a stable medication regimen, requiring at least one mood stabilizer
  • Depression severity as represented by scoring at least 20 on MADRS
  • Meet the safety criteria as defined in the transcranial magnetic stimulation adult safety screen (TASS).

Exclusion Criteria:

  • No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary)
  • Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation)
  • No dementia or other major neurological disorders
  • Not having depression as primary disorder
  • No major medical illness, for example metastatic cancer, end stage renal disease
  • Not able to verify contact information. Participants must be able to follow through with the study & must have verified contact information and at least one verified contact
  • Pregnancy. While there are no known risks to a fetus this is a new use of TMS, which has not been tested, thus pregnancy is exclusionary
  • Score on YMRS greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment (Tavares et al., 2021).
  • Rapid cycling Bipolar illness (patients with > 4 mood episodes within the past year will be excluded, as they have a higher risk of switch to mania (Tondo et al., 2010)
  • Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI

Sites / Locations

  • UCSD Interventional PsychiatryRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active iTBS

Sham iTBS

Arm Description

Patients will receive unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions.

Patients will receive sham unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions.

Outcomes

Primary Outcome Measures

Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Montgomery-Asberg Depression Rating Scale (MADRS) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression.
Change in Hamilton Rating Scale for Depression (HRSD-17) Scores
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Hamilton Rating Scale for Depression (HRSD-17) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 53, with higher scores indicating more severe depression.
Assessment of Biomarkers
Analysis of transcranial magnetic stimulation concurrent with electroencephalogram (TMS-EEG) to extract effective connectivity metrics between the subgenual cingulate (SGC) and the left dorsolateral prefrontal cortex (DLPFC) as BPD biomarkers, as measured by scores on the HAMD and MADRS, for aiTBS compared to sham treatment.

Secondary Outcome Measures

Full Information

First Posted
May 5, 2022
Last Updated
May 8, 2023
Sponsor
University of California, San Diego
Collaborators
University of Pennsylvania, Milken Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05393648
Brief Title
Bipolar Efficacy Biomarkers for rTMS
Official Title
Bipolar Efficacy Biomarkers for Accelerated Intermittent Theta Burst rTMS Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
University of Pennsylvania, Milken Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of repetitive transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression (BPD) who have failed (or not shown signs of improvement) after at least two prior treatments. The null hypothesis is that there will be no difference in reductions in depressive symptoms by the end of a five-day treatment period. The alternative hypothesis is that, compared with sham, active TMS will result in a greater reduction in depressive symptoms by the end of the treatment period. To facilitate the development of rTMS protocols there is a need for biomarkers that are sensitive to BPD symptom severity and clinical improvement. Previously in our lab, investigators developed biomarkers suitable for depression trials, and these biomarkers are very likely to show sensitivity to BPD, since they are associated with brain regions and functions associated with BPD. As a secondary aim, the investigators will try to identify biomarkers in cortical region associated with BPD, and formulate a statistical model that may be able to predict BPD remission after the treatment. this study will lead to development of new brain stimulation treatment protocols and biomarkers, will aid in treatment selection, and eventually lead to better clinical outcome for patients suffering from BPD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder, Bipolar Depression
Keywords
theta burst stimulation, accelerated TBS

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients enrolled in the study will be randomized to sham vs. active accelerated iTBS in a 1:1 ratio. Treatments will be over 1 week.
Masking
ParticipantOutcomes Assessor
Masking Description
A sham component will be used over the right DLPFC for unilateral aiTBS treatment. This treatment component will mitigate concerns of expectancy, and will lead to blinding for patients. The Cool B65 A/P coil is unmarked, with one side producing active treatment and the other sham treatment with concurrent electrical stimulation, which accurately mimics active stimulation.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active iTBS
Arm Type
Experimental
Arm Description
Patients will receive unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions.
Arm Title
Sham iTBS
Arm Type
Placebo Comparator
Arm Description
Patients will receive sham unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions.
Intervention Type
Device
Intervention Name(s)
Accelerated Theta Burst Stimulation
Intervention Description
Cool B65- A/P - active side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex.
Intervention Type
Device
Intervention Name(s)
Sham accelerated Theta Burst Stimulation
Intervention Description
Cool-B65 A/P - sham side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex.
Primary Outcome Measure Information:
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Description
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Montgomery-Asberg Depression Rating Scale (MADRS) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression.
Time Frame
6 months
Title
Change in Hamilton Rating Scale for Depression (HRSD-17) Scores
Description
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Hamilton Rating Scale for Depression (HRSD-17) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 53, with higher scores indicating more severe depression.
Time Frame
6 months
Title
Assessment of Biomarkers
Description
Analysis of transcranial magnetic stimulation concurrent with electroencephalogram (TMS-EEG) to extract effective connectivity metrics between the subgenual cingulate (SGC) and the left dorsolateral prefrontal cortex (DLPFC) as BPD biomarkers, as measured by scores on the HAMD and MADRS, for aiTBS compared to sham treatment.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Bipolar depression (BP I and BP II) by DSM 5 criteria (Diagnostic and Statistical Manual of Mental Disorders, 2013) Age 18-70 Right or left handed All genders Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria (Sackeim et al., 2019) Able to provide informed consent to participate in the study Must be on a stable medication regimen, requiring at least one mood stabilizer Depression severity as represented by scoring at least 20 on MADRS Meet the safety criteria as defined in the transcranial magnetic stimulation adult safety screen (TASS). Exclusion Criteria: No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary) Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation) No dementia or other major neurological disorders Not having depression as primary disorder No major medical illness, for example metastatic cancer, end stage renal disease Not able to verify contact information. Participants must be able to follow through with the study & must have verified contact information and at least one verified contact Pregnancy. While there are no known risks to a fetus this is a new use of TMS, which has not been tested, thus pregnancy is exclusionary Score on YMRS greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment (Tavares et al., 2021). Rapid cycling Bipolar illness (patients with > 4 mood episodes within the past year will be excluded, as they have a higher risk of switch to mania (Tondo et al., 2010) Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Interventional Psychiatry
Phone
8582070938
Email
iptrials@health.ucsd.edu
Facility Information:
Facility Name
UCSD Interventional Psychiatry
City
San Diego
State/Province
California
ZIP/Postal Code
92127
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Interventional Psychiatry
Phone
858-207-0938
Email
iptrials@health.ucsd.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Bipolar Efficacy Biomarkers for rTMS

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