Comparisons of Prefrontal Inhibition and Excitation Between Prefrontal Intermittent Theta-Burst Stimulation and 10-Hz Repetitive Transcranial Magnetic Stimulation for Treating Refractory Depression: A Sham-Control Neuroimaging Study

UMIN ID: UMIN000055955

Registered date:28/10/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: The evidence so far suggests that inhibitory function, such as GABAa-receptor-related and GABAb-receptor-related inhibitory function in the DLPFC, is key to treatment responses in MDD. Prolonged intermittent theta-burst stimulation(piTBS) could be effective through the modulation of prefrontal excitatory and inhibitory function. In addition, previous literature provided the evidence that 2-weeks left-sided DLPFC-piTBS had similar antidepressant efficacy with the 4-6weeks standard left-sided DLPFC-10HzrTMS. However, the following questions remain to be answered: (1)4-weeks left-sided DLPFC-piTBS could provide better antidepressant efficacy than 4-weeks left-sided DLPFC-10HzrTMS; (2)the potentially different effects of 4-weeks piTBS and rTMS on PFC inhibitory functions, and (3) the identification of reliable biomarkers, including EEG signals, that could reliably predict the antidepressant effects of 4-weeks rTMS/piTBS intervention.
• Date of first enrollment: 2024/10/28
• Target sample size: 60
• Countries of recruitment: Asia(except Japan)
• Study type: Interventional

Intervention(s)

Group A (piTBS group): A three-pulse 50Hz wave delivered every 200ms at 80% active motor threshold, with stimulation for 2 seconds followed by an 8-second rest, for 60 cycles, totaling 1800 pulses/session, for a total of 20 sessions(4 weeks)
Group B (10Hz rTMS group): 10Hz at 120% resting motor threshold, with stimulation for 4 seconds followed by a 16-second rest, for 75 cycles, totaling 3000 pulses/session, for a total of 20 sessions(4 weeks)
Sham group: half of the patients following the parameters of Group A and the other half following the parameters of Group B, but stimulated by standard sham coil (Magstim(R)), for a total of 20 sessions(4 weeks)

Outcome(s)

• Primary Outcome: Improvement in depression severity, measured by a percentage change in 17-items Hamilton Depression Rating Scale(HDRS-17) score (% HDRS-17) before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham).
• Secondary Outcome: 1. The response rate (defined as a >= 50% reduction compared with the baseline HDRS-17 score) and the remission rate (defined as an HDRS-17 score <= 7). 2. Safety 3. the changes of TMS-EEG parameters before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham) 4. the changes of regional brain glucose metabolism before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham) 5. the changes of prefrontal EEG before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham) 6. the changes of cognitive function, measured by Test of Attentional Performance and Go-Nogo test, before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham) 7. the changes of functional connectivities before and after 4 weeks of brain stimulation treatment between the three groups (piTBS,10HzrTMS and sham) 8. the correlation between antidepressant efficacy and baseline prefrontal function, measured by EEG, TMS-EEG indices and glucose metabolism and functional connectivities and EEG. 9. the correlation between antidepressant efficacy and baseline mood-related brain area, measured by glucose metabolism and functional connectivities. 10. the correlation between antidepressant efficacy and the changes of glucose metabolism and functional connectivities on the mood-related brain area. 11. the correlation between antidepressant efficacy and the changes of TMS-EEG and EEG indices on prefrontal cortex. 12. the correlation between antidepressant efficacy and patients' characteristic (e.g., treatment refractoriness)

Key inclusion & exclusion criteria

• Age minimum: 21years-old
• Age maximum: 70years-old
• Gender: Male and Female
• Exclude criteria: (1)A lifetime psychiatric diagnosis of psychotic disorder, bipolar disorder, organic mental disorder, substance use disorder (based on DSM-IV criteria), and a lifetime medical history of major systemic illness and neurological disorder records(e.g., seizure, cerebrovascular disease, stroke, meningitis and traumatic brain injury) (2)A history of brain surgery, brain implants (e.g., neurostimulators, clip), and cardiac pacemakers and any mental device or implant in the body (e.g. neurostimulators, electrodes, cochlear implant) (3)Any major brain organic insults (e.g., brain arteriovenous malformation, cerebral aneurysm, primary or secondary tumors in central nervous system) (4)Having active suicidal intent, or high suicidality if score of the third item of HDRS-17 is 4 in recent one week. (5)Women in pregnancy. (6)Claustrophobia: people cannot stay in a closed environment (e.g., MRI scan) (7)Presence of any other condition that has the potential to prevent study completion or may confound the outcome assessments (e.g. refusal to sign the informed consent, no meet the inclusion criteria after recruitment)

Related Information

• Primary Sponsor: Taipei Veterans General Hospital, Taipei, Taiwan
• Source(s) of Monetary Support: Taipei Veterans General Hospital, Taipei, Taiwan