Canadian rTMS Treatment and Biomarker Network in Depression Trial (CARTBIND)

• ClinicalTrials.gov Identifier: NCT02729792
• Recruitment Status: Completed
• First Posted: April 6, 2016
• Last Update Posted: July 26, 2018
• Sponsor: Centre for Addiction and Mental Health
• Collaborators: University Health Network, Toronto; University of British Columbia; Brain Canada
• Information provided by (Responsible Party): Daniel Blumberger, Centre for Addiction and Mental Health

Study Description

Brief Summary:

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for medically refractory major depressive disorder (MDD). rTMS involves direct stimulation of cortical neurons using externally applied, powerful, focused magnetic field pulses. Dozens of studies and several meta-analyses over the last 15 years have shown that rTMS of the dorsolateral prefrontal cortex (DLPFC) produces statistically significant improvements in MDD, even when medications have failed. However, other possible targets may also yield improvement in symptoms.

In an attempt to enhance the therapeutic efficacy of current interventions for TRD, attention has turned to identifying domain-specific biomarkers in hopes of ultimately individualizing and predicting treatment response. Unfortunately, the precise nature of this relationship is less than clear, as reflected by the fact that even now there are no established biomarkers that are used routinely in clinical practice to aid in diagnosis. This study also seeks to examine a comprehensive suite of biomarker measurements (MRI, neurophysiology, and genomics/proteomics) before and after rTMS treatment.

Condition or disease	Intervention/treatment	Phase
Depression	Device: rTMS	Not Applicable

Detailed Description:

rTMS is a Health-Canada- and FDA-approved treatment for treatment-resistant depression (TRD), using focused magnetic field pulses to stimulate brain regions involved in emotion regulation, safely and non-invasively. Though rTMS is often effective where medications or therapy fail, it requires a series of lengthy (~30-40 min) treatment sessions. A new form of rTMS called theta burst stimulation (TBS) has been shown to have greater effects on neural activity than conventional stimulation, despite requiring as little as 40 s of stimulation. The purpose of this study is to assess the efficacy and tolerability of an accelerated TBS protocol, administered 2 times a day in patients with TRD. In addition, the investigators aim to identify candidate biomarkers from a multimodal suite of neuroimaging, neurophysiologic and molecular measures that are predictors and correlates of response to rTMS treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Canadian rTMS Treatment and Biomarker Network in Depression Trial
• Study Start Date: March 2016
• Actual Primary Completion Date: February 23, 2018
• Actual Study Completion Date: May 30, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single site rTMS; Each treatment session will consist of: 1200 pulses of iTBS over a posterior target location followed by a 60 minute interval, then 1200 pulses of iTBS over an anterior target location.	Device: rTMS; intermittent theta burst stimulation (iTBS)
Active Comparator: Dual site rTMS; Each treatment session will consist of: 600 pulses of iTBS over the posterior target, followed immediately by 600 pulses of iTBS over the anterior target location followed by a 60 minute interval, then 600 pulses of iTBS over the posterior target, followed immediately by 600 pulses of iTBS over the anterior target location.	Device: rTMS; intermittent theta burst stimulation (iTBS)

Outcome Measures

Primary Outcome Measures :

1. 17-item Hamilton Rating Scale for Depression (HRSD-17) Change [ Time Frame: 10 days ]
   Change from baseline to 10 days

Secondary Outcome Measures :

1. 17-item Hamilton Rating Scale for Depression (HRSD-17) Change [ Time Frame: 30 days ]
   Change from baseline to 30 days

Other Outcome Measures:

1. Beck Depression Inventory-II Change [ Time Frame: 10 days ]
   Change from baseline to 10 days
2. Quick Inventory of Depressive Symptoms Change [ Time Frame: 10 days ]
   Change from baseline to 10 days
3. 17-item Hamilton Rating Scale for Depression (HRSD-17) Remission [ Time Frame: 10 days ]
   Remission rates defined as a HRSD-17 < 8 at 10 days
4. Beck Depression Inventory-II [ Time Frame: 30 days ]
   Change from baseline to 30 days
5. Quick Inventory of Depressive Symptoms Change [ Time Frame: 30 Days ]
   Change from baseline to 30 days
6. 17-item Hamilton Rating Scale for Depression (HRSD-17) Remission [ Time Frame: 30 days ]
   Remission rates defined as a HRSD-17 < 8 at 30 days
7. 17-item Hamilton Rating Scale for Depression (HRSD-17) Response [ Time Frame: 10 days ]
   Response rates defined as a HRSD-17 decrease > 50% at 10 days
8. 17-item Hamilton Rating Scale for Depression (HRSD-17) Response [ Time Frame: 30 days ]
   Response rates defined as a HRSD-17 decrease > 50% at 10 days

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 59 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. are outpatients
2. are voluntary and competent to consent to treatment
3. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent
4. are between the ages of 18 and 59
5. have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of > 3 in the current episode 105,106 OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants)
6. have a score > 18 on the HRSD-17 item
7. have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
8. able to adhere to the treatment schedule
9. Pass the TMS adult safety screening (TASS) questionnaire
10. have normal thyroid functioning based on pre-study blood work.

Exclusion Criteria:

1. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of substance dependence or abuse within the last 3 months
2. have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
3. have active suicidal intent
4. are pregnant
5. have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms
6. have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD
7. have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
8. have failed a course of ECT in the current episode or previous episode
9. have received rTMS for any previous indication due to the potential compromise of subject blinding
10. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes
11. have an intracranial 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
12. if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
13. clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians
14. currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy
15. non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Contacts and Locations

Locations

Canada, British Columbia

Non-Invasive Neurostimulation Therapies Centre, University of British Columbia

Vancouver, British Columbia, Canada, V6T 2A1

Canada, Ontario

Toronto Western Hospital

Toronto, Ontario, Canada, M5T 2S8

Centre for Addiction and Mental Health

Toronto, Ontario, Canada, M6J 1H4

Sponsors and Collaborators

Centre for Addiction and Mental Health

University Health Network, Toronto

University of British Columbia

Brain Canada

Investigators

• Principal Investigator: Daniel M. Blumberger, MD, MSc; CAMH

More Information

Additional Information:

The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Blumberger DM, Vila-Rodriguez F, Wang W, Knyahnytska Y, Butterfield M, Noda Y, Yariv S, Isserles M, Voineskos D, Ainsworth NJ, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Brain Stimul. 2021 Nov-Dec;14(6):1447-1455. doi: 10.1016/j.brs.2021.09.003. Epub 2021 Sep 21.

• Responsible Party: Daniel Blumberger, Medical Head and Co-Director, Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health
• ClinicalTrials.gov Identifier: NCT02729792
• Other Study ID Numbers: 052-2015
• First Posted: April 6, 2016
• Last Update Posted: July 26, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Daniel Blumberger, Centre for Addiction and Mental Health:

depression; treatment resistance; biomarkers; repetitive transcranial magnetic stimulation

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders