Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study

Treatment Resistant Depression Clinical Trial

Official title:

Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03680781
• Other study ID #: IRB-44150
• Status: Enrolling by invitation
• Phase: N/A
• Start date: April 13, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 90
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

Device:
• Intermittent theta-burst stimulation (iTBS)
Participants will receive iTBS to the left DLPFC or bilateral DLPFC, to the right and left DLPFC. The DLPFC will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the L-DLPFC or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device.

Locations

Country	Name	City	State
United States	Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage change in Hamilton Depression Rating Scale 21-Item score	A 21 item clinical assessment tool used to rate a patient's level of depression - total scores range from 0-63 with higher scores indicating worse depression	Difference between baseline and one month after aiTBS treatment
Secondary	Change in Hamilton Rating Scale for Depression (HAMD-17)	A provider administered questionnaire used to rate a patient's level of depression - total scores range from 0-52 with higher scores indicating worse depression	Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment
Secondary	Change in The Scale for Suicide Ideation	A rating scale that measures the current intensity of specific attitudes, behaviors, and plans to commit suicide - total scores range from 0-38 with higher scores indicating greater suicidality	Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment
Secondary	Change in Hamilton Rating Scale for Depression (HAMD-6)	rate a patient's level of depression - total scores range from 0-22 with higher scores indicating worse depression	Every day of stimulation, follow-up every 2 weeks after treatment for 6 months by telephone]
Secondary	Change from baseline functional connectivity	We will assess functional connectivity as seen on resting state fMRI, between the subcallosal cingulate to the default mode network and within the default mode network.	Pretreatment, immediately post-treatment, 4 weeks post-treatment
Secondary	Change in Beck Depression Inventory (BDI)	Self-report measure of depressive symptoms - total scores range from 0-63 with higher scores indicating worse depression	Pretreatment, immediately post-treatment, 4 weeks post-treatment
Secondary	Change in Montgomery-Åsberg Depression Rating Scale (MADRS)	A 10 item clinician rated measure of depressive symptoms - total scores range from 0-60 with higher scores indicating worse depression	Pretreatment, immediately post-treatment, 4 weeks post-treatment