Clinical trial NCT02749006: Efficacy of rTMS in Bipolar Depression
Official title: A Randomized Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in Acute Bipolar Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Bipolar Depression
Keywords: Bipolar disorder
Depression
intermittent Theta-Burst Stimulation (rTMS)
neuromodulatory technique
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2016-04-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Montgomery Asberg Depression Rating Scale (MADRS) Scale Score
timeFrame: Baseline, Week 2, Week 4
Secondary outcomes:
measure: Number of Participants With Clinical Response
timeFrame: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
measure: Number of Participants Meeting Criteria for Clinical Remission
timeFrame: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)
measure: Overall Well Being
timeFrame: Baseline to 4 weeks
measure: Brief Illness Perception Questionnaire
timeFrame: Baseline to 4 weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: Baseline to 4 weeks
measure: Quality of Life Questionnaire
timeFrame: Baseline to 4 weeks
measure: Patient Global Impression Rating Scale: Severity
timeFrame: Baseline to 4 weeks
measure: Patient Global Impression Rating Scale- Improvement
timeFrame: Week 4
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Dr. Alexander McGirr
state: Alberta
city: Vancouver
country: Canada
facility: Djavad Mowfaghian Centre for Brain Heath
state: British Columbia
Study officials:
affiliation: Regional Head and Program Medical Director,
name: Lakshmi Yatham, MBBS,FRCPsy
role: STUDY_DIRECTOR
References:
citation: 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.