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Efficacy of rTMS in Bipolar Depression (rTMS-BD)

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ClinicalTrials.gov Identifier: NCT02749006
Recruitment Status : Recruiting
First Posted : April 22, 2016
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Jayasree Basivireddy, University of British Columbia

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.

Condition or disease Intervention/treatment Phase
Bipolar Depression Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS) Device: Sham rTMS Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-blind Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in Acute Bipolar Depression
Study Start Date : April 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.
Device: 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.
Other Name: MAGPRO X100 stimulator

Sham Comparator: 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.
Device: Sham rTMS
Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.
Other Name: MAGPRO X100 stimulator




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline to 4 weeks ]
    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 :
  1. Improvement in mood from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group. [ Time Frame: Baseline to 4 weeks ]
    Young Mania Rating Scale (YMRS) will be used to assess changes in mood from baseline to Week 4.

  2. Improvement in overall psychiatric status from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group. [ Time Frame: Baseline to 4 weeks ]
    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).

  3. Improvement in overall well being from baseline to week 4 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group. [ Time Frame: Baseline to 4 weeks ]
    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.

  4. 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. [ Time Frame: Baseline to 4 weeks ]
    Brief Illness Perception Questionnaire that captures the difficulty in functioning major life activities on a scale of 0 (not at all ) to 9 (severely).

  5. Improvement in neurocognitive function from baseline to week-4 (post rTMS treatment) with iTBS-rTMS as compared to sham [ Time Frame: Baseline to 4 weeks ]
    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).

  6. 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 [ Time Frame: Baseline to 4 weeks ]
    CFQ captures minor mistakes of daily functioning at a scale of 0 (never) to 4 (very often) making mistakes.

  7. 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. [ Time Frame: Baseline to 4 weeks ]
    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).

  8. 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. [ Time Frame: Baseline to 4 weeks ]
    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).

  9. Patient Global Impression Rating Scale: Severity and Improvement [ Time Frame: Baseline to 4 weeks ]
    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).



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02749006


Contacts
Contact: Jayasree Basivireddy, PhD. 604-822-3769 jayasree.basivireddy@ubc.ca

Locations
Canada, British Columbia
Djavad Mowfaghian Centre for Brain Heath Recruiting
Vancouver, British Columbia, Canada, V6T 1Z3
Contact: Sharon Ahn, BA    604-822-7320    sharon.ahn@ubc.ca   
Contact: Nazlin Walji, B.Sc,CCRC    604-822-7294    nazlin.walji@ubc.ca   
Principal Investigator: Lakshmi Yatham         
Sponsors and Collaborators
University of British Columbia
Investigators
Study Director: Lakshmi Yatham, MBBS,FRCPC,MRCPsych Regional Head and Program Medical Director, Mental Health and Addictions, Vancouver Coastal Health and Providence Health Care Professor, Department of Psychiatry, University of British Columbia

Responsible Party: Jayasree Basivireddy, Clinical Research Coordinator, University of British Columbia
ClinicalTrials.gov Identifier: NCT02749006     History of Changes
Other Study ID Numbers: H16-00259
First Posted: April 22, 2016    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Jayasree Basivireddy, University of British Columbia:
Bipolar disorder
Depression
intermittent Theta-Burst Stimulation (rTMS)
neuromodulatory technique

Additional relevant MeSH terms:
Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders