Efficacy of rTMS in Bipolar Depression (rTMS-BD)

January 17, 2025 updated by: Lakshmi N Yatham, University of British Columbia

A Randomized Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in Acute Bipolar Depression

Bipolar Disorder is a common condition that is characterized by periods of mood elevation however periods of chronic and recurring depressive episodes are more common and can be severely disabling. Effective treatments exist, however a significant portion of bipolar depressed patients do not respond to, or have difficulty tolerating many of these interventions. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulatory technique that is effective in major depression and there is evidence for its efficacy in bipolar depression which needs to be assessed in larger randomized controlled trials. This study is a randomised, double-blind, sham-controlled trial over four weeks. The primary objective is to assess improvement in depressive symptoms in acute bipolar depressed patients on treatment with intermittent Theta-Burst Stimulation (iTBS) in comparison to sham-rTMS.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

rTMS is a treatment that involves stimulating a certain area of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of bipolar depression. The device used in this study has been approved by Health Canada for therapeutic use since 2002. Participants will complete a screen visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible subjects will be randomized to receive either active iTBS-rTMS or sham rTMS treatment (scalp stimulation with no magnetic pulse) daily for four weeks (20 sessions) to the left dorsolateral prefrontal cortex (DLPFC). All participants will complete a MRI (to target the left DLPFC region of the brain and functional activity), EEG & fNIRS, lab work, and neurocognitive testing prior to the commencement and post rTMS treatment. Efficacy, safety and tolerability will be evaluated at screen visit, during daily rTMS treatments, clinic visits and post rTMS treatment. All participants will have a phone interview two weeks post rTMS treatment.

Study Type

Interventional

Enrollment (Actual)

37

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 Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • Dr. Alexander McGirr
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 1Z3
        • Djavad Mowfaghian Centre for Brain Heath

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

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Are a male or female aged 18 to 70 years.
  • Have a diagnosis of Bipolar Disorder with a current ongoing episode of depression.
  • Are not currently experiencing a mania.
  • Have failed to achieve a clinical response or have been unable to tolerate an adequate dose of at least one of the medications used for treating Bipolar depression
  • Are taking an anti-manic agent (lithium or valproate) or an atypical antipsychotic (quetiapine, lurasidone, aripiprazole, ziprasidone, risperidone, olanzapine), or a combination of the above, or a combination of any of them with lamotrigine 100-400 mg daily. Lamotrigine alone for bipolar II disorder is permitted.
  • current medications have been at a stable dose in the 2 weeks prior to randomization
  • Are capable of understanding, consenting to, and complying with the requirements of the study

Exclusion criteria:

  • Have an alcohol or substance abuse or dependence within the last 3 months.
  • Are at a significant risk of harm to themselves or others
  • Are pregnant or planning on becoming pregnant in near future or lactating.
  • Have a personal or family history of seizures.
  • Have a history of unstable or inadequately treated medical illnesses, including moderate to severe brain injury or head trauma.
  • Have a primary diagnosis of other psychiatric disorders (other than Bipolar) or personality disorders that are of primary concern and causing greater impairment other than bipolar disorder.
  • are currently taking more than 3 of the antipsychotics.
  • Have failed a course of ECT in the current episode.
  • History of non-response to rTMS treatment.
  • If participating in psychotherapy, you must have been in stable treatment for at least 3 months prior to entry into the study,
  • Currently (or in the last 4 weeks) taking more than 2 mg daily (or equivalent) of lorazepam or any dose of medication for seizures
  • Have a pacemaker, or an implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth that cannot be safely removed.
  • 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
Active Comparator: Active iTBS rTMS
The active arm involves magnetic stimulation of the brain to the left dorsolateral prefrontal cortex (DLPFC) daily for four weeks. The active arm will be receiving intermittent Theta-Burst (iTBS) repetitive Transcranial Magnetic Stimulation (rTMS) to deliver magnetic pulses.
Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS)
rTMS is a non-invasive procedure in which cerebral electrical activity is influenced by a rapidly changing magnetic field. The magnetic field is created by a plastic-encased coil which is placed over the patient's scalp. The magnetic field can be directed onto specific areas of the brain. rTMS can modulate cerebral activity by low or high frequencies. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of bipolar depression.
Other Names:
  • MAGPRO X100 stimulator
Sham Comparator: Sham rTMS
sham rTMS treatment involves scalp stimulation with no magnetic pulse daily for four weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.
Device: Sham rTMS
Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.
Other Names:
  • MAGPRO X100 stimulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery Asberg Depression Rating Scale (MADRS) Scale Score
Time Frame: Baseline, Week 2, Week 4
The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. A higher score means a worse outcome. Min value is 0, Max value is 60
Baseline, Week 2, Week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Clinical Response
Time Frame: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
Response rates are defined as patients showing ≥50% reduction in MADRS scores.
Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
Number of Participants Meeting Criteria for Clinical Remission
Time Frame: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
Clinical Remission is defined as a MADRS score ≤12
Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
Overall Well Being
Time Frame: Baseline to 4 weeks
The visual analog scale (VAS) is a self report measure that captures the over all well being. Min 0-worse health to Max 100- best health.
Baseline to 4 weeks
Brief Illness Perception Questionnaire
Time Frame: Baseline to 4 weeks
Brief Illness Perception Questionnaire measures participant's perception of illness. Min = 0 Max = 80. Higher score means worse outcome.
Baseline to 4 weeks
Sheehan Disability Scale (SDS)
Time Frame: Baseline to 4 weeks
The Sheehan Disability Scale is a five-item, self-rated questionnaire designed to measure the extent to which a patient's disability due to an illness interferes with work/school, social life/leisure activities, and family life/home responsibilities. Each subscale score (a work disability, a social life disability, a family life disability) is combined into a single total score (sum of the non missing responses for items 1-3) representing a global impairment rating, ranging from 0 to 30, with higher scores indicative of significant functional impairment.
Baseline to 4 weeks
Quality of Life Questionnaire
Time Frame: Baseline to 4 weeks
The Quality of Life in Bipolar Disorder scale is a 56 item scale which assesses 12 core and 2 optional (work and study) domains, each containing four self-report items (1: strongly disagree to 5: strongly agree). An overall score (range: 48-240) may be calculated by summing responses to the 48 items of the core 12 domains. Higher scores reflect greater satisfaction with a person's quality of life.
Baseline to 4 weeks
Patient Global Impression Rating Scale: Severity
Time Frame: Baseline to 4 weeks
Patient Global Impression Rating Scale: Severity rates how depressed the participant is at the current time. 1-4 (1 is normal and 4 is severe)
Baseline to 4 weeks
Patient Global Impression Rating Scale- Improvement
Time Frame: Week 4
Rates current depression compared to baseline. Min =1 Max =7 Higher scores mean worse outcome.
Week 4

Collaborators and Investigators

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

Sponsor

University of British Columbia

Investigators

  • Study Director: Lakshmi Yatham, MBBS,FRCPsy, Regional Head and Program Medical Director,

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

October 5, 2016

Primary Completion (Actual)

April 30, 2020

Study Completion (Actual)

December 30, 2020

Study Registration Dates

First Submitted

March 18, 2016

First Submitted That Met QC Criteria

April 21, 2016

First Posted (Estimated)

April 22, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 17, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H16-00259

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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