Back to resultsEfficacy of rTMS in Bipolar Depression (rTMS-BD)
Primary Purpose
Bipolar Depression
Status
Terminated
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
iTBS repetitive Transcranial Magnetic Stimulation (rTMS)
Sham rTMS
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Depression focused on measuring Bipolar disorder, Depression, intermittent Theta-Burst Stimulation (rTMS), neuromodulatory technique
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).
Sites / Locations
- Dr. Alexander McGirr
- Djavad Mowfaghian Centre for Brain Heath
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active iTBS rTMS
Sham rTMS
Arm Description
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 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.
Outcomes
Primary Outcome Measures
Improvement in depressive symptoms as measured by MADRS scale score from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group
Compared to sham-rTMS, active-iTBS rTMS is anticipated to show Higher rates of clinical remission (score ≤12 on the MADRS) and Higher rates of clinical response (≥50% reduction in MADRS scores) in patients with acute bipolar depression.
Secondary Outcome Measures
Improvement in mood from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Young Mania Rating Scale (YMRS) will be used to assess changes in mood from baseline to Week 4.
Improvement in overall psychiatric status from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Clinical Global Impression severity and change scale - bipolar version (CGI-BP) is a clinician rated scale to capture any change in participants mania, depression, over well being in a a single scale 1 (normal not at all ill) to 7 (very severely ill).
Improvement in overall well being from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
The visual analog scale (VAS) is self report measure captures the over all being from of 0-worst health to 100- best health. We are only the sub scale of VAS to capture the over all well being.
BFIS self report questionnaire that captures the difficulty in functioning major life activities from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Brief Illness Perception Questionnaire that captures the difficulty in functioning major life activities on a scale of 0 (not at all ) to 9 (severely).
Improvement in neurocognitive function from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham
Cognitive improvement will be measured by changes in cognitive score on The International Society for Bipolar Disorders-Battery for Assessment of Neurocognition (ISBD-BANC) from baseline to week-4 (post rTMS treatment).
Cognitive Failures Questionnaire (CFQ)is a self report questionnaire to capture daily cognitive measures from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham
CFQ captures minor mistakes of daily functioning at a scale of 0 (never) to 4 (very often) making mistakes.
Sheehan Disability Scale (SDS) is a self report questionnaire to assess everyday functioning will be assessed from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham.
Sheehan Disability Scale is to capture everyday functioning at work/school, social life, family life and home responsibilities captured in a scale of 0 to 10 (not at all to extremely disruptive).
Quality of Life questionnaire is a self report questionnaire improvement in life quality to assess baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham.
Quality of Life in Bipolar Disorder (QoL.BD) captures a range of experiences, behaviors, felling related questions scaled from 1 (strongly disagree) to 5 (strongly agree).
Patient Global Impression Rating Scale: Severity and Improvement
Patient Global Impression Rating Scale: Severity and Improvement is a self-rated scale to capture any change in participants mood rating 1-4 (1 is normal and 4 is severe) and improvement rating of 1-7 (1 is very much better and 7 is very much worse).
Full Information
NCT ID
NCT02749006
First Posted
March 18, 2016
Last Updated
March 2, 2021
Sponsor
University of British Columbia
1. Study Identification
Unique Protocol Identification Number
NCT02749006
Brief Title
Efficacy of rTMS in Bipolar Depression
Acronym
rTMS-BD
Official Title
A Randomized Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in Acute Bipolar Depression
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Hard to enroll
Study Start Date
April 2016 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
December 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Depression
Keywords
Bipolar disorder, Depression, intermittent Theta-Burst Stimulation (rTMS), neuromodulatory technique
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active iTBS rTMS
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Sham rTMS
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
iTBS repetitive Transcranial Magnetic Stimulation (rTMS)
Other Intervention Name(s)
MAGPRO X100 stimulator
Intervention Description
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
Intervention Name(s)
Sham rTMS
Other Intervention Name(s)
MAGPRO X100 stimulator
Intervention Description
Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.
Primary Outcome Measure Information:
Title
Improvement in depressive symptoms as measured by MADRS scale score from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group
Description
Compared to sham-rTMS, active-iTBS rTMS is anticipated to show Higher rates of clinical remission (score ≤12 on the MADRS) and Higher rates of clinical response (≥50% reduction in MADRS scores) in patients with acute bipolar depression.
Time Frame
Baseline to 4 weeks
Secondary Outcome Measure Information:
Title
Improvement in mood from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Description
Young Mania Rating Scale (YMRS) will be used to assess changes in mood from baseline to Week 4.
Time Frame
Baseline to 4 weeks
Title
Improvement in overall psychiatric status from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Description
Clinical Global Impression severity and change scale - bipolar version (CGI-BP) is a clinician rated scale to capture any change in participants mania, depression, over well being in a a single scale 1 (normal not at all ill) to 7 (very severely ill).
Time Frame
Baseline to 4 weeks
Title
Improvement in overall well being from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Description
The visual analog scale (VAS) is self report measure captures the over all being from of 0-worst health to 100- best health. We are only the sub scale of VAS to capture the over all well being.
Time Frame
Baseline to 4 weeks
Title
BFIS self report questionnaire that captures the difficulty in functioning major life activities from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group.
Description
Brief Illness Perception Questionnaire that captures the difficulty in functioning major life activities on a scale of 0 (not at all ) to 9 (severely).
Time Frame
Baseline to 4 weeks
Title
Improvement in neurocognitive function from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham
Description
Cognitive improvement will be measured by changes in cognitive score on The International Society for Bipolar Disorders-Battery for Assessment of Neurocognition (ISBD-BANC) from baseline to week-4 (post rTMS treatment).
Time Frame
Baseline to 4 weeks
Title
Cognitive Failures Questionnaire (CFQ)is a self report questionnaire to capture daily cognitive measures from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham
Description
CFQ captures minor mistakes of daily functioning at a scale of 0 (never) to 4 (very often) making mistakes.
Time Frame
Baseline to 4 weeks
Title
Sheehan Disability Scale (SDS) is a self report questionnaire to assess everyday functioning will be assessed from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham.
Description
Sheehan Disability Scale is to capture everyday functioning at work/school, social life, family life and home responsibilities captured in a scale of 0 to 10 (not at all to extremely disruptive).
Time Frame
Baseline to 4 weeks
Title
Quality of Life questionnaire is a self report questionnaire improvement in life quality to assess baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham.
Description
Quality of Life in Bipolar Disorder (QoL.BD) captures a range of experiences, behaviors, felling related questions scaled from 1 (strongly disagree) to 5 (strongly agree).
Time Frame
Baseline to 4 weeks
Title
Patient Global Impression Rating Scale: Severity and Improvement
Description
Patient Global Impression Rating Scale: Severity and Improvement is a self-rated scale to capture any change in participants mood rating 1-4 (1 is normal and 4 is severe) and improvement rating of 1-7 (1 is very much better and 7 is very much worse).
Time Frame
Baseline to 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lakshmi Yatham, MBBS,FRCPsy
Organizational Affiliation
Regional Head and Program Medical Director,
Official's Role
Study Director
Facility Information:
Facility Name
Dr. Alexander McGirr
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
Djavad Mowfaghian Centre for Brain Heath
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 1Z3
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33710288
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.
Results Reference
derived
Learn more about this trial
Efficacy of rTMS in Bipolar Depression
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