Theta-Burst Stimulation for Bipolar Depression (TRIBE)

March 16, 2026 updated by: Tyler Kaster, Centre for Addiction and Mental Health
The purpose of this trial is to determine if intermittent theta-burst stimulation (iTBS) can reduce the symptoms of depression in treatment-resistant bipolar disorder. To do this, some of the participants in this study will receive treatment with active iTBS stimulation, while others will receive sham iTBS stimulation. Participants will come for 30 days of either active iTBS or sham iTBS, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M6J 1H4
        • Recruiting
        • Centre for Addiction and Mental Health
        • Contact:
        • Principal Investigator:
          • Tyler Kaster, M.D., Ph.D
      • Toronto, Ontario, Canada, M5T 2S8
        • Recruiting
        • University Health Network
        • Contact:
        • Principal Investigator:
          • Daphne Voineskos, M.D., Ph.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

The participant must meet all of the inclusion criteria to eligible for this clinical trial:

  1. Must be deemed to have capacity to provide informed consent;
  2. Must be an outpatient
  3. Have a DSM 5 diagnosis of bipolar disorder (type I or II), current episode depressed confirmed by Mini-International Neuropsychiatric Interview version 7.0.2 (MINI);
  4. Age 18-65;
  5. failure to achieve a clinical response to ≥1 adequate treatment trial for bipolar depression based on the Antidepressant Treatment History Form - Short Form (ATHF-SF) OR unable to tolerate at least 2 separate inadequate treatment trials for bipolar depression;43
  6. moderately severe depression with a score ≥ 15 on the PHQ-9;44
  7. not currently experiencing a mixed or manic episode (YMRS ≤10);
  8. no increase or initiation of psychotropic medication with intention of treating depressive symptoms in the 4 weeks prior to screening. This excludes targeted treatment of insomnia with trazodone, melatonin, low-dose doxepin [3-6mg], low-dose benzodiazepines [≤2mg lorazepam daily equivalent], non-benzodiazepine benzodiazepine receptor agonists, or orexin antagonists;
  9. able to adhere to the treatment schedule;
  10. pass the TMS adult safety screening questionnaire.45

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this clinical trial:

  1. have a history of MINI diagnosis of a substance use disorder (other than nicotine and/or caffeine) within the last 3 months;
  2. have a concomitant major unstable medical illness;
  3. have active suicidal intent (assessed during HRSD-17 Item 3 and SSRS as imminent intent to act on specific plan, confirmed by psychiatric staff);
  4. are pregnant or intend to get pregnant during the study;
  5. have a lifetime MINI diagnosis of schizophrenia or schizoaffective disorder;
  6. have psychotic symptoms within the current episode;
  7. have a MINI anxiety disorder, trauma-related disorder, obsessive compulsive disorder, or personality disorder assessed by a study investigator to be primary and/or causing greater impairment than BD-DE;
  8. failure of an adequate acute course of ECT as defined by ATHF-SF during the current episode;
  9. have received any rTMS before due to potential to compromise blinding of treatment allocation;
  10. have any clinically significant neurological disorder (e.g., recent major cerebrovascular accident), or any history of seizure except those therapeutically induced by ECT or with clear precipitant (e.g., febrile seizure of childhood, alcohol withdrawal, etc.);
  11. have any intracranial implant (e.g., aneurysm clips, shunts, stimulators,) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
  12. are participating in psychotherapy for less than 3 months. Patients will be permitted if they have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;
  13. are currently taking lorazepam >2 mg daily (or equivalent) due to the potential to limit rTMS efficacy;
  14. are currently taking any dose of an anticonvulsant due to the potential to limit rTMS efficacy. If anticonvulsants have been discontinued prior to screening, at least 5 half-lives have elapsed until screening to allow sufficient drug clearance;
  15. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham iTBS Stimulation
Administered once daily over 30 days, using a sham coil that reproduces auditory and tactile sensations of stimulation and has an identical external appearance. Each session will deliver 600 pulses of sham iTBS in triplet 50Hz bursts, repeated at 5Hz 2s on 8s off for a total time of ~3 minutes, 9 seconds at a target intensity of 120% of the subject's resting motor threshold.
Device: Sham iTBS Stimulation
Fluid-Cooled B70 A/P Coil with either Magventure X100 or R30
Experimental: Active iTBS Stimulation
Administered once daily over 30 days. Each session will deliver 600 pulses of active iTBS in triplet 50Hz bursts, repeated at 5Hz 2s on 8s off for a total time of ~3 minutes, 9 seconds at a target intensity of 120% of the subject's resting motor threshold.
Device: iTBS Stimulation
Fluid-Cooled B70 A/P Coil with either Magventure X100 or R30

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
Time Frame: From enrollment to 6 weeks post-treatment
Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17), ITT, 6 weeks (completion of treatment phase (30 txs)). The main effect of interest is the interaction term between time since starting treatment and treatment allocation. This analytic approach incorporates longitudinal depressive symptom assessments throughout the trial rather solely at treatment completion.
From enrollment to 6 weeks post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptoms of Mania
Time Frame: From enrollment to 6 weeks post-treatment
Safety of rTMS in BD-DE with respect to symptoms of mania, Young Mania Rating Scale (YMRS), Safety Outcomes, 6 weeks (completion of treatment phase (30 txs)). The main effect of interest is the interaction term between time since starting treatment and treatment allocation. This analytic approach incorporates longitudinal depressive symptom assessments throughout the trial rather solely at treatment completion.
From enrollment to 6 weeks post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Addiction and Mental Health

Collaborators

University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2024

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

April 15, 2024

First Submitted That Met QC Criteria

April 15, 2024

First Posted (Actual)

April 17, 2024

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4343 (Company internal)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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