Clinical trial NCT01887782: Randomized Controlled Trial of Conventional vs Theta Burst rTMS
Official title: A Randomized Controlled Study of Conventional Versus Theta Burst Repetitive Transcranial Magnetic Stimulation in the Treatment of Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: depression
magnetic
brain stimulation
treatment-resistant
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2013-06-27
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will compare a novel form of rTMS, intermittent Theta Burst Stimulation to the standard conventional high frequency left sided stimulation protocol. The Left dorsolateral prefrontal cortex will be the site of stimulation in both treatment conditions. The site of stimulation will be targeted using MRI co-registration. The study seeks to determine if the two treatment protocols have similar effectiveness in treating major depression.


Eligibility criteria: Inclusion Criteria:

* outpatients
* voluntary and competent to consent
* Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single, recurrent
* between ages 18-65
* failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2)
* have a score of ≥ 18 on the HAMD-17 item
* have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
* able to adhere to the treatment schedule
* Pass the TMS adult safety screening (TASS) questionnaire
* have normal thyroid functioning based on pre-study blood work

Exclusion Criteria:

* have a history of substance dependence or abuse within the last 3 months
* have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
* have active suicidal intent
* are pregnant
* have a lifetime MINI diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform, delusional disorder, or current psychotic symptoms
* 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

Primary outcomes:
measure: HAM-D17 score
timeFrame: baseline, after each 5 treatment sessions, and 1, 4, and 12 weeks post-treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Non-Invasive Neurostimulation Therapies Centre, University of British Columbia
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Daniel Blumberger, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto Western Hospital
name: Jonathan Downar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Fidel Vila-Rodriguez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Trevizol AP, Downar J, Vila-Rodriguez F, Thorpe KE, Daskalakis ZJ, Blumberger DM. Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: An analysis from the randomised non-inferiority THREE-D trial. EClinicalMedicine. 2020 Apr 30;22:100349. doi: 10.1016/j.eclinm.2020.100349. eCollection 2020 May.
citation: Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Vila-Rodriguez F. Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up. Brain Stimul. 2020 Jan-Feb;13(1):206-214. doi: 10.1016/j.brs.2019.10.012. Epub 2019 Oct 18.
citation: Hsu JH, Downar J, Vila-Rodriguez F, Daskalakis ZJ, Blumberger DM. Impact of prior treatment on remission with intermittent theta burst versus high-frequency repetitive transcranial magnetic stimulation in treatment resistant depression. Brain Stimul. 2019 Nov-Dec;12(6):1553-1555. doi: 10.1016/j.brs.2019.07.011. Epub 2019 Jul 17.
citation: Kaster TS, Downar J, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Blumberger DM. Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study. Am J Psychiatry. 2019 May 1;176(5):367-375. doi: 10.1176/appi.ajp.2018.18091096. Epub 2019 Feb 15.
citation: Shalbaf R, Brenner C, Pang C, Blumberger DM, Downar J, Daskalakis ZJ, Tham J, Lam RW, Farzan F, Vila-Rodriguez F. Non-linear Entropy Analysis in EEG to Predict Treatment Response to Repetitive Transcranial Magnetic Stimulation in Depression. Front Pharmacol. 2018 Oct 30;9:1188. doi: 10.3389/fphar.2018.01188. eCollection 2018.
citation: Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.