Efficacy of rTMS in Bipolar Depression

NCT02749006 | Terminated Results

• 1 other identifier: H16-00259
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

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.

Conditions

Bipolar Depression

Keywords

Bipolar disorder; Depression; intermittent Theta-Burst Stimulation (rTMS); neuromodulatory technique

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, Week 2, Week 4

Secondary Outcomes (8)

• Number of Participants With Clinical Response

  Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)

• Number of Participants Meeting Criteria for Clinical Remission

  Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)

• Overall Well Being

  Baseline to 4 weeks

• Brief Illness Perception Questionnaire

  Baseline to 4 weeks

• Sheehan Disability Scale (SDS)

  Baseline to 4 weeks

Study Arms (2)

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.

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.

Device: Sham rTMS

Interventions

iTBS repetitive Transcranial Magnetic Stimulation (rTMS) 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.

Also known as: MAGPRO X100 stimulator

Active iTBS rTMS

Sham rTMS DEVICE

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

Also known as: MAGPRO X100 stimulator

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (2)

Dr. Alexander McGirr

Calgary, Alberta, T2N 4Z6, Canada

Location

Djavad Mowfaghian Centre for Brain Heath

Vancouver, British Columbia, V6T 1Z3, Canada

Location

Related Publications (2)

• 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.

  PMID: 36924413 DERIVED

• 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.

  PMID: 33710288 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Depression

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Limitations and Caveats

This study is limited by a modest sample size; however, this is the direct consequence of premature termination after interim analyses indicated futility.

Results Point of Contact

• Title: Dr. Lakshmi Yatham
• Organization: University Of British Columbia

l.yatham@ubc.ca

604-822-7310

Study Officials

• Lakshmi Yatham, MBBS,FRCPsy

  Regional Head and Program Medical Director,

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: April 22, 2016
• Study Start: October 5, 2016
• Primary Completion: April 30, 2020
• Study Completion: December 30, 2020
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)