Efficacy of rTMS in Bipolar Depression

NCT ID: NCT02749006

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-05
• Study Completion Date: 2020-12-30

Brief Summary

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

iTBS repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type: DEVICE

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 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.

Group Type: SHAM_COMPARATOR

Sham rTMS

Intervention Type: DEVICE

Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Interventions

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.

Intervention Type: DEVICE

Sham rTMS

Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Intervention Type: DEVICE

Other Intervention Names

MAGPRO X100 stimulator; MAGPRO X100 stimulator

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Lakshmi N Yatham

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lakshmi Yatham, MBBS,FRCPsy

Role: STUDY_DIRECTOR

Regional Head and Program Medical Director,

Locations

Dr. Alexander McGirr

Calgary, Alberta, Canada

Djavad Mowfaghian Centre for Brain Heath

Vancouver, British Columbia, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 36924413 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33710288 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

H16-00259

Identifier Type: -

Identifier Source: org_study_id