Bipolar DepressionrTMS-BDNCT02749006

Efficacy of rTMS in Bipolar Depression

A study testing iTBS repetitive Transcranial Magnetic Stimulation (rTMS) in people with Bipolar Depression, run by University of British Columbia at 2 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Bipolar Depression
What is being tested?: iTBS repetitive Transcranial Magnetic Stimulation (rTMS)
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 37 participants
Where: 2 sitesCanada
Study dates: 5 Oct 2016to 30 Dec 2020
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Show all 13Show fewer

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).

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

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

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Conditions: Bipolar Depression
Being tested: iTBS repetitive Transcranial Magnetic Stimulation (rTMS), Sham rTMS
Keywords: Bipolar disorder, Depression, intermittent Theta-Burst Stimulation (rTMS), neuromodulatory technique
Medical subject headings: Bipolar Disorder, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

iTBS repetitive Transcranial Magnetic Stimulation (rTMS)Device
Also called MAGPRO X100 stimulator
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.
Sham rTMSDevice
Also called MAGPRO X100 stimulator
Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Study groups in NCT02749006
Study group	Role	What they receive
Active iTBS rTMS	Active comparator	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. Receives: Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS)
Sham rTMS	Sham comparator	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. Receives: Device: Sham rTMS

What is being measured

The primary outcome is the main question the study is designed to answer.

Montgomery Asberg Depression Rating Scale (MADRS) Scale Score
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
Measured: Baseline, Week 2, Week 4

Secondary outcomes (8)

Number of Participants With Clinical Response
Response rates are defined as patients showing ≥50% reduction in MADRS scores.
Measured: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
Number of Participants Meeting Criteria for Clinical Remission
Clinical Remission is defined as a MADRS score ≤12
Measured: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
Overall Well Being
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.
Measured: Baseline to 4 weeks
Brief Illness Perception Questionnaire
Brief Illness Perception Questionnaire measures participant's perception of illness. Min = 0 Max = 80. Higher score means worse outcome.
Measured: Baseline to 4 weeks
Sheehan Disability Scale (SDS)
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.
Measured: Baseline to 4 weeks
Quality of Life Questionnaire
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.
Measured: Baseline to 4 weeks
Patient Global Impression Rating Scale: Severity
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)
Measured: Baseline to 4 weeks
Patient Global Impression Rating Scale- Improvement
Rates current depression compared to baseline. Min =1 Max =7 Higher scores mean worse outcome.
Measured: Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Oct 201630 Dec 2020

First posted22 Apr 2016 (estimated)
Study start5 Oct 2016
Primary completion30 Apr 2020
Study completion30 Dec 2020

Why it stopped: Unable to enroll the planned number of participants.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Bipolar DepressionStudies of the same condition, open and under way.
More trials run by University of British ColumbiaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02749006
Sponsor's protocol ID: H16-00259
Acronym: rTMS-BD
Status last verified: Jan 2025
First submitted: 18 Mar 2016
Last updated: 10 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Torres IJ, Ge R, McGirr A, Vila-Rodriguez F, Ahn S, Basivireddy J, Walji N, Frangou S, Lam RW, Yatham LN. Effects of intermittent theta-burst transcranial magnetic stimulation on cognition and hippocampal volumes in bipolar depression. Dialogues Clin Neurosci. 2023 Dec;25(1):24-32. doi: 10.1080/19585969.2023.2186189.
PubMed 36924413
McGirr A, Vila-Rodriguez F, Cole J, Torres IJ, Arumugham SS, Keramatian K, Saraf G, Lam RW, Chakrabarty T, Yatham LN. Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial. JAMA Netw Open. 2021 Mar 1;4(3):e210963. doi: 10.1001/jamanetworkopen.2021.0963.
PubMed 33710288

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in Acute Bipolar Depression
ClinicalTrials.gov ID: NCT02749006
Acronym / sponsor ID: rTMS-BD / H16-00259
Conditions: Bipolar Depression
Keywords: Bipolar disorder, Depression, intermittent Theta-Burst Stimulation (rTMS), neuromodulatory technique
Study type: Interventional
Recruitment status: TerminatedReason stopped: Unable to enroll the planned number of participants.
Enrolment: 37 participants (actual)
Lead sponsor: University of British ColumbiaUniversity, hospital or other
Study start: 5 Oct 2016 (actual)
Primary completion: 30 Apr 2020 (actual)
Study completion: 30 Dec 2020 (actual)
First posted: 22 Apr 2016 (estimated)
Results: Posted 10 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Active iTBS rTMS	Active comparator	Device: iTBS repetitive Transcranial Magnetic Stimulation (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.
Sham rTMS	Sham comparator	Device: Sham rTMSsham 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (13 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
iTBS repetitive Transcranial Magnetic Stimulation (rTMS)Also: MAGPRO X100 stimulatorrTMS 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.	Device	Active iTBS rTMS
Sham rTMSAlso: MAGPRO X100 stimulatorSham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.	Device	Sham rTMS

Primary outcome

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

8 secondary outcomes

Number of Participants With Clinical Response
Time frame: 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)
Overall Well Being
Time frame: Baseline to 4 weeks
Brief Illness Perception Questionnaire
Time frame: Baseline to 4 weeks
Sheehan Disability Scale (SDS)
Time frame: Baseline to 4 weeks
Quality of Life Questionnaire
Time frame: Baseline to 4 weeks
Patient Global Impression Rating Scale: Severity
Time frame: Baseline to 4 weeks
Patient Global Impression Rating Scale- Improvement
Time frame: Week 4

Results and safety

Results posted to the registry on 10 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active iTBS rTMS	18	15
Sham rTMS	19	16

Primary outcome: Montgomery Asberg Depression Rating Scale (MADRS) Scale Score

Time frame: Baseline, Week 2, Week 4. Mean (Standard Deviation). Unit: score on a scale

Measure	Active iTBS rTMS n = 18	Sham rTMS n = 19
Baseline	32.27 (4.04)	31.52 (5.22)
Week 2	24.12 (10.09)	25.17 (8.24)
Week 4	24.46 (10.82)	23.06 (10.58)

Population analysed: Diagnosis of BD type I or type II by Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria, experiencing a major depressive episode (MDE).

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to 4 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active iTBS rTMS	0 of 18 (0%)	7 of 7 (100%)	0 of 18
Sham rTMS	0 of 19 (0%)	9 of 9 (100%)	0 of 19

Limitations and caveats (from the sponsor): This study is limited by a modest sample size; however, this is the direct consequence of premature termination after interim analyses indicated futility.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36924413Torres IJ, Ge R, McGirr A, Vila-Rodriguez F, Ahn S, Basivireddy J, Walji N, Frangou S, Lam RW, Yatham LN. Effects of intermittent theta-burst transcranial magnetic stimulation on cognition and hippocampal volumes in bipolar depression. Dialogues Clin Neurosci. 2023 Dec;25(1):24-32. doi: 10.1080/19585969.2023.2186189.
Derived from this study: PubMed 33710288McGirr A, Vila-Rodriguez F, Cole J, Torres IJ, Arumugham SS, Keramatian K, Saraf G, Lam RW, Chakrabarty T, Yatham LN. Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial. JAMA Netw Open. 2021 Mar 1;4(3):e210963. doi: 10.1001/jamanetworkopen.2021.0963.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lakshmi Yatham, MBBS,FRCPsy study director

Regional Head and Program Medical Director,

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing iTBS repetitive Transcranial Magnetic Stimulation (rTMS) in people with Bipolar Depression, run by University of British Columbia at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montgomery Asberg Depression Rating Scale (MADRS) Scale Score (time frame: Baseline, Week 2, Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02749006, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.