Ignite Creation Date:
2024-05-06 @ 8:28 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06392867
Status:
RECRUITING
Last Update Posted:
2024-05-01
First Post:
2024-04-23
Brief Title:
Intermittent Theta-burst Stimulation for Major Depression an Intensity-response Study
Sponsor:
The Hong Kong Polytechnic University
Organization:
The Hong Kong Polytechnic University
Study Overview
Official Title:
Intermittent Theta-burst Stimulation for Major Depression an Intensity-response Study
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The United States Food and Drug Administration FDA approved intermittent theta-burst stimulation iTBS in 2018 as a form of repetitive transcranial magnetic stimulation rTMS Hospitals worldwide use it to treat major depressive disorder MDD It is safe effective even for depressed patients unable to respond to standard pharmacological treatment and is more efficient than standard rTMS In accordance with the approved treatment protocol patients experience considerable sensory discomfort at a stimulation intensity of 120 of their resting motor threshold rMT Antidepressant effects of iTBS are believed to be mediated by modulating prefrontal excitability There is still a lack of evidence to support the choice of 120 rMT as the optimal stimulation intensity and the presumed superiority of higher stimulation intensities over lower intensities has yet to be proven This knowledge gap has clinical implications since more tolerated treatments may lead to greater adherence resulting in improved outcomes
The current study proposes a randomized triple-arm controlled trial to compare the efficacy of iTBS at 75 iTBS75 and 120 iTBS120 rMT with sham iTBS SiTBS Based on the following considerations SiTBS was selected to be compared with iTBS75 and iTBS120 SiTBS will reveal placebo antidepressant effects and serve as a control iTBS75 is selected because iTBS at 80 aMT exhibits significant excitatory effects on the motor cortex and corresponds to approximately 70 rMT There is however a distance of about 127mm between the coil and the motor cortex whereas 144mm separates the coil from the dorsolateral prefrontal cortex DLPFC Accordingly a resting motor threshold of 70 at the motor cortex corresponds to a distance-adjusted rMT of 75 at the DLPFC Lastly iTBS120 is chosen as the standard stimulation intensity in current iTBS depression trials
It is our intention to investigate the potential antidepressant effects of iTBS treatment at a much lower stimulation intensity than the one currently employed by most centers in the United States and approved in these centers Thus our study can contribute to establishing a treatment regimen with increased adherence and lower withdrawal rates
The current study proposes a randomized triple-arm controlled trial to compare the efficacy of iTBS at 75 iTBS75 and 120 iTBS120 rMT with sham iTBS SiTBS Based on the following considerations SiTBS was selected to be compared with iTBS75 and iTBS120 SiTBS will reveal placebo antidepressant effects and serve as a control iTBS75 is selected because iTBS at 80 aMT exhibits significant excitatory effects on the motor cortex and corresponds to approximately 70 rMT There is however a distance of about 127mm between the coil and the motor cortex whereas 144mm separates the coil from the dorsolateral prefrontal cortex DLPFC Accordingly a resting motor threshold of 70 at the motor cortex corresponds to a distance-adjusted rMT of 75 at the DLPFC Lastly iTBS120 is chosen as the standard stimulation intensity in current iTBS depression trials
It is our intention to investigate the potential antidepressant effects of iTBS treatment at a much lower stimulation intensity than the one currently employed by most centers in the United States and approved in these centers Thus our study can contribute to establishing a treatment regimen with increased adherence and lower withdrawal rates
Detailed Description:
Introduction
Key issues and knowledge gaps Intermittent theta-burst stimulation iTBS a special form of patterned repetitive transcranial magnetic stimulation rTMS approved by the US Food and Drug Administration in 2018 is frequently used in many hospitals worldwide for the treatment of major depressive disorder MDD For example at the Department of Psychiatry and Psychotherapy Medical University of Vienna we perform about four iTBS treatments daily amounting to about 1000 treatments a year iTBS is safe effective even in depressed patients that are refractory to standard pharmacological treatments and has the advantage of increased efficiency over standard rTMS The approved treatment protocol involves a stimulation intensity of 120 of the individuals resting motor threshold rMT an intensity associated with considerable sensory discomfort for patients
The application of a stimulation intensity of 120 rMT is common practice in many psychiatric TMS clinics and is based on research with conventional rTMS indicating higher clinical efficacy with higher stimulation intensity However neuroplastic effects of iTBS of the motor cortex are generally observed at much lower intensities Researchers have observed significant excitatory effects of iTBS when the intensity is 80 of active motor threshold aMT which is approximately 70 of reactive motor threshold rMT Moreover the assumption that the neuromodulatory effects are greater with increasing stimulation intensity is highly debated and recent research indicates that a linear dose-response relationship for prefrontal iTBS is unfounded Yet modulation of prefrontal excitability is thought to underlie the antidepressant effect of iTBS We still lack evidence for the choice of 120 rMT as the optimal intensity and the presumed superiority of higher stimulation strengths over lower intensities is yet to be investigated This is a knowledge gap that has important clinical implications because more tolerable treatments could result in greater adherence and therefore ultimately better outcomes
Here we propose a randomized multicentre triple-arm controlled clinical trial to compare the efficacy of a 4-week treatment of daily iTBS at 75 iTBS75 and 120 iTBS120 rMT compared to sham iTBS SiTBS The choice to compare SiTBS with iTBS75 and iTBS120 is based on the following considerations SiTBS will reveal placebo antidepressant effects and serves as a control condition iTBS75 is chosen because iTBS at 80 aMT shows significant excitatory effects of the motor cortex and equals approximately 70 rMT However the distance from the coil to the motor cortex is on average 127mm whereas the distance to the dorsolateral prefrontal cortex DLPFC is about 144 mm Hence a resting motor threshold of 70 at the motor cortex corresponds to a distance-adjusted rMT of approximately 75 at the DLPFC Finally iTBS120 is chosen as it is the standard stimulation intensity in current iTBS trials for depression
Our proposed study will elucidate the potential antidepressant effect of iTBS treatment at a much lower stimulation intensity than that currently employed by most centres and approved in the US Hence our study has a high potential to pave the way towards establishing a treatment regimen with increased adherence and lower rates of withdrawal
Aims and Hypotheses to be tested
This randomized multicentre triple-arm controlled clinical trial aims to compare the efficacy of SiTBS with iTBS75 and iTBS120 after four weeks of daily treatments in patients with MDD We hypothesize that iTBS75 will be more effective in reducing depressive symptoms compared with SiTBS and iTBS120 More specifically 1 we hypothesize that the rate of response defined as a reduction of Montgomery-Asberg Depression Rating Scale MADRS score to 50 of baseline values after treatment is significantly higher for iTBS75 compared to sham stimulation and iTBS120 primary hypothesis In a secondary analysis we will test the hypothesis that 2 the rate of remission defined as a final MADRS score of 8 over the course of four weeks of treatment is significantly higher for iTBS75 compared to the other two arms Similarly we hypothesise that the increase of 3 subjective mood and 4 happiness assessed using PHQ-9 and SHS respectively is significantly higher for iTBS75 compared to the other two arms Finally we hypothesize that 5 iTBS75 is more tolerable than iTBS120 as indicated by a lower reported pain sensation during iTBS75 compared to iTBS120
Key issues and knowledge gaps Intermittent theta-burst stimulation iTBS a special form of patterned repetitive transcranial magnetic stimulation rTMS approved by the US Food and Drug Administration in 2018 is frequently used in many hospitals worldwide for the treatment of major depressive disorder MDD For example at the Department of Psychiatry and Psychotherapy Medical University of Vienna we perform about four iTBS treatments daily amounting to about 1000 treatments a year iTBS is safe effective even in depressed patients that are refractory to standard pharmacological treatments and has the advantage of increased efficiency over standard rTMS The approved treatment protocol involves a stimulation intensity of 120 of the individuals resting motor threshold rMT an intensity associated with considerable sensory discomfort for patients
The application of a stimulation intensity of 120 rMT is common practice in many psychiatric TMS clinics and is based on research with conventional rTMS indicating higher clinical efficacy with higher stimulation intensity However neuroplastic effects of iTBS of the motor cortex are generally observed at much lower intensities Researchers have observed significant excitatory effects of iTBS when the intensity is 80 of active motor threshold aMT which is approximately 70 of reactive motor threshold rMT Moreover the assumption that the neuromodulatory effects are greater with increasing stimulation intensity is highly debated and recent research indicates that a linear dose-response relationship for prefrontal iTBS is unfounded Yet modulation of prefrontal excitability is thought to underlie the antidepressant effect of iTBS We still lack evidence for the choice of 120 rMT as the optimal intensity and the presumed superiority of higher stimulation strengths over lower intensities is yet to be investigated This is a knowledge gap that has important clinical implications because more tolerable treatments could result in greater adherence and therefore ultimately better outcomes
Here we propose a randomized multicentre triple-arm controlled clinical trial to compare the efficacy of a 4-week treatment of daily iTBS at 75 iTBS75 and 120 iTBS120 rMT compared to sham iTBS SiTBS The choice to compare SiTBS with iTBS75 and iTBS120 is based on the following considerations SiTBS will reveal placebo antidepressant effects and serves as a control condition iTBS75 is chosen because iTBS at 80 aMT shows significant excitatory effects of the motor cortex and equals approximately 70 rMT However the distance from the coil to the motor cortex is on average 127mm whereas the distance to the dorsolateral prefrontal cortex DLPFC is about 144 mm Hence a resting motor threshold of 70 at the motor cortex corresponds to a distance-adjusted rMT of approximately 75 at the DLPFC Finally iTBS120 is chosen as it is the standard stimulation intensity in current iTBS trials for depression
Our proposed study will elucidate the potential antidepressant effect of iTBS treatment at a much lower stimulation intensity than that currently employed by most centres and approved in the US Hence our study has a high potential to pave the way towards establishing a treatment regimen with increased adherence and lower rates of withdrawal
Aims and Hypotheses to be tested
This randomized multicentre triple-arm controlled clinical trial aims to compare the efficacy of SiTBS with iTBS75 and iTBS120 after four weeks of daily treatments in patients with MDD We hypothesize that iTBS75 will be more effective in reducing depressive symptoms compared with SiTBS and iTBS120 More specifically 1 we hypothesize that the rate of response defined as a reduction of Montgomery-Asberg Depression Rating Scale MADRS score to 50 of baseline values after treatment is significantly higher for iTBS75 compared to sham stimulation and iTBS120 primary hypothesis In a secondary analysis we will test the hypothesis that 2 the rate of remission defined as a final MADRS score of 8 over the course of four weeks of treatment is significantly higher for iTBS75 compared to the other two arms Similarly we hypothesise that the increase of 3 subjective mood and 4 happiness assessed using PHQ-9 and SHS respectively is significantly higher for iTBS75 compared to the other two arms Finally we hypothesize that 5 iTBS75 is more tolerable than iTBS120 as indicated by a lower reported pain sensation during iTBS75 compared to iTBS120
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None