Clinical trial NCT03680781: Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study
Official title: Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Treatment Resistant Depression
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2018-09-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.

Detailed description: Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study will investigate the efficacy of a further modified protocol, creating a more rapid form of the treatment and look at the change in neuroimaging biomarkers. In particular, this study will determine the efficacy of re-treatment in individuals who have already experienced benefit of the accelerated protocol to ensure results can be repeated.

Eligibility criteria: Inclusion Criteria:

* Male or female, 18 to 75 years of age.
* Able to provide informed consent.
* Diagnosed with Major Depressive Disorder (MDD) or bipolar affective disorder 2 and currently experiencing a Major Depressive Episode (MDE).
* prior exposure to rTMS
* Participants must qualify as "moderate or severe treatment refractory" using the Maudsley staging method.
* Participants may continue antidepressant regimen, but must be stable for 6 weeks prior to enrollment in the study. They must maintain that same antidepressant regimen throughout the study duration.
* Participants are required to have a stable psychiatrist for the duration of study enrollment.

Exclusion Criteria:

* History of MI, CABG, CHF, or other cardiac history
* Any neurological conditions
* History of epilepsy
* OCD
* Independent sleep disorder
* Autism Spectrum Disorder

Primary outcomes:
measure: Percentage change in Hamilton Depression Rating Scale 21-Item score
timeFrame: Difference between baseline and one month after aiTBS treatment
Secondary outcomes:
measure: Change in Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment
measure: Change in The Scale for Suicide Ideation
timeFrame: Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment
measure: Change in Hamilton Rating Scale for Depression (HAMD-6)
timeFrame: Every day of stimulation, follow-up every 2 weeks after treatment for 6 months by telephone]
measure: Change from baseline functional connectivity
timeFrame: Pretreatment, immediately post-treatment, 4 weeks post-treatment
measure: Change in Beck Depression Inventory (BDI)
timeFrame: Pretreatment, immediately post-treatment, 4 weeks post-treatment
measure: Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Pretreatment, immediately post-treatment, 4 weeks post-treatment
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Gregory Sahlem, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
citation: George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
citation: Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
citation: Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.
citation: Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.
citation: Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.