Ignite Creation Date:
2024-05-06 @ 10:33 AM
Last Modification Date:
2024-10-26 @ 12:32 PM
Study NCT ID:
NCT03289923
Status:
RECRUITING
Last Update Posted:
2024-02-29
First Post:
2017-09-20
Brief Title:
Concurrent fMRI-guided rTMS and Cognitive Therapy for the Treatment of Major Depressive Episodes
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Concurrent fMRI-guided rTMS and Cognitive Therapy for the Treatment of Major Depressive Episodes
Status:
RECRUITING
Status Verified Date:
2024-09-11
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:
Background
Repetitive transcranial magnetic stimulation rTMS is a treatment for depression It stimulates the brain Researchers want to see if using magnetic resonance imaging MRI scans helps locate the best area for rTMS in each person They also want to find other ways to make it more effective
Objective
To study the effects of combining MRI- guided transcranial magnetic stimulation TMS and talk therapy on the brain in people with depression
Eligibility
Adults ages 18-75 with a major depressive disorder and current depression If taking an antidepressant should have been doing so for at least 4 weeks
Design
Participants will be screened with medical and psychiatric history psychiatric evaluation physical exam and blood and urine tests
Phase 1 is 1-4 visits in 1 week Participants will have
Brain MRI Participants will lie on a table in a scanner
Questions about their medical history and psychology symptoms
Tests of mood and thinking
Tests of brain activity Participants may do tasks during these tests
A cone with magnetic detectors is put on the head
A cap with electrodes is put on the scalp
TMS A brief electrical current passes through a wire coil on the scalp
A metal disk will be placed on the arm A nerve will be stimulated with a small electrical shock
Phase 2 is about 6 to 7 weeks
There will be 30 daily sessions of combined therapy and repetitive TMS rTMS for 6 weeks
Participants will receive rTMS and another therapy by computer
For rTMS repeated pulses will pass through the coil
This is followed by up to 3 additional visits when
Participants will repeat Phase 1 tests
Participants will rate their depression symptoms
Phase 3 is 3 visits over 3 months Participants will rate their depression symptoms and repeat some of the previous questionnaires and tests of mood and thinking
Repetitive transcranial magnetic stimulation rTMS is a treatment for depression It stimulates the brain Researchers want to see if using magnetic resonance imaging MRI scans helps locate the best area for rTMS in each person They also want to find other ways to make it more effective
Objective
To study the effects of combining MRI- guided transcranial magnetic stimulation TMS and talk therapy on the brain in people with depression
Eligibility
Adults ages 18-75 with a major depressive disorder and current depression If taking an antidepressant should have been doing so for at least 4 weeks
Design
Participants will be screened with medical and psychiatric history psychiatric evaluation physical exam and blood and urine tests
Phase 1 is 1-4 visits in 1 week Participants will have
Brain MRI Participants will lie on a table in a scanner
Questions about their medical history and psychology symptoms
Tests of mood and thinking
Tests of brain activity Participants may do tasks during these tests
A cone with magnetic detectors is put on the head
A cap with electrodes is put on the scalp
TMS A brief electrical current passes through a wire coil on the scalp
A metal disk will be placed on the arm A nerve will be stimulated with a small electrical shock
Phase 2 is about 6 to 7 weeks
There will be 30 daily sessions of combined therapy and repetitive TMS rTMS for 6 weeks
Participants will receive rTMS and another therapy by computer
For rTMS repeated pulses will pass through the coil
This is followed by up to 3 additional visits when
Participants will repeat Phase 1 tests
Participants will rate their depression symptoms
Phase 3 is 3 visits over 3 months Participants will rate their depression symptoms and repeat some of the previous questionnaires and tests of mood and thinking
Detailed Description:
Objective
Despite the growing use of repetitive transcranial magnetic stimulation rTMS as a treatment for unipolar major depression its typical effect sizes have been modest and both methodological and conceptual challenges remain regarding how to optimize its efficacy Two key elements have been missing from current work first to take an RDoC approach and link the treatment to a comprehensive model of the neurocircuitry underlying depression where applying such a model to personalize the site of stimulation is likely to significantly improve the efficacy of rTMS and second to maximize neural changes to the engaged depression network by utilizing cognitive paired associate stimulation C-PAS a technique we have developed over the last decade in which noninvasive stimulation is applied to the targeted region while the circuit is engaged in processing related to desired behavior here through the simultaneous use of cognitive behavioral therapy The concurrent firing in the emotional regulation circuit caused by TMS pulses and by the CBT will lead to neural plasticity according to the Hebbian conception of fire together wire together while repeated stimulation over the course of multiple TMS sessions will induce neuroplasticity to accelerate and strengthen those changes which are expected to be therapeutic We thus intend to test a novel integrative multimodal treatment for MDD consisting of a theory-based protocol for individualized optimization of rTMS site of stimulation plus concurrent behavioral interventions targeting the same dysfunctional neural circuitry Our targeting procedure is based on recent developments in the psychology and neurobiology of self-regulation which offer a promising conceptual framework for identifying neural network mechanisms of action in rTMS for depression as well as for developing guidelines for individualized rTMS treatment As preliminary data we report initial feasibility data from a clinical paradigm in which five adults with major depressionreceived TMS to the left middle frontal gyrus targeted on an individual basis using fMRI while simultaneously receiving a previously validated self-regulation-based psychotherapy Here we will test this individualized method in a larger randomized trial
Study Population
The study population will consist of 50 individuals between the 18 and 65 years of age with a diagnosis of treatment-resistant Major Depressive Disorder MDD
Study Design
This single site study is a proof-of-concept clinical trial to test both functional states associated with an antidepressant response to a six week course of C-PAS using concomitant SST and 10 Hz rTMS neuronavigated to left DLPFC as well as the feasibility and safety of such a course for long-term improvement in depressive symptoms The proposed study will be conducted over 3 phases Phase I will consist of screening consent and baseline measures Screening will occur under the ETPB screening protocol 01-M-0254 Phase II will consist of a 6-week double-blind sham controlled trial of neuronavigated TMS cognitive therapy Participants will be randomized to two groups receiving either Active or Sham fMRI-guided-TMS while involved in a cognitive therapy session Subjects will participate in 30 daily sessions over 6 weeks with MRI sessions both prior to and immediately after the course of TMS Additionally MEG may optionally be performed at baseline immediately after the first TMSSST session and immediately after the entire course of TMS and an optional battery of TMSEEG excitability and plasticity measures may be performed pre- and post-TMSSST course In Phase III the study team will provide standard of care for depression for up to three months and will prescribe a relapse prevention strategy in consultation with the referring physician including TMS which is consistent with standard of care
Outcome Measures
Primary outcome measures are change in magnitude of BOLD signal recorded in pre- and post-TMS course MRI sessions in the DLPFC region targeted with TMS based on individual activations in that region found at baseline using the priming task and pre- and post-TMS course connectivity changes between DLPFC measured with DTI and resting state functional connectivity and other regions associated with the emotional regulation network specifically OFC medial PFC precuneus and ACC Pre and post TMS course change in depression severity scores HDRS MADRS will also be found in order to look for correlations with these MRI measures Secondary outcome measures will be ratings from the BSL C-SSRS CTQ HAM-A NIH-BFI PANAS RBANS RRS SHAPS and TLEQ as well as electrophysiological changes using MEG and EEG measures
Despite the growing use of repetitive transcranial magnetic stimulation rTMS as a treatment for unipolar major depression its typical effect sizes have been modest and both methodological and conceptual challenges remain regarding how to optimize its efficacy Two key elements have been missing from current work first to take an RDoC approach and link the treatment to a comprehensive model of the neurocircuitry underlying depression where applying such a model to personalize the site of stimulation is likely to significantly improve the efficacy of rTMS and second to maximize neural changes to the engaged depression network by utilizing cognitive paired associate stimulation C-PAS a technique we have developed over the last decade in which noninvasive stimulation is applied to the targeted region while the circuit is engaged in processing related to desired behavior here through the simultaneous use of cognitive behavioral therapy The concurrent firing in the emotional regulation circuit caused by TMS pulses and by the CBT will lead to neural plasticity according to the Hebbian conception of fire together wire together while repeated stimulation over the course of multiple TMS sessions will induce neuroplasticity to accelerate and strengthen those changes which are expected to be therapeutic We thus intend to test a novel integrative multimodal treatment for MDD consisting of a theory-based protocol for individualized optimization of rTMS site of stimulation plus concurrent behavioral interventions targeting the same dysfunctional neural circuitry Our targeting procedure is based on recent developments in the psychology and neurobiology of self-regulation which offer a promising conceptual framework for identifying neural network mechanisms of action in rTMS for depression as well as for developing guidelines for individualized rTMS treatment As preliminary data we report initial feasibility data from a clinical paradigm in which five adults with major depressionreceived TMS to the left middle frontal gyrus targeted on an individual basis using fMRI while simultaneously receiving a previously validated self-regulation-based psychotherapy Here we will test this individualized method in a larger randomized trial
Study Population
The study population will consist of 50 individuals between the 18 and 65 years of age with a diagnosis of treatment-resistant Major Depressive Disorder MDD
Study Design
This single site study is a proof-of-concept clinical trial to test both functional states associated with an antidepressant response to a six week course of C-PAS using concomitant SST and 10 Hz rTMS neuronavigated to left DLPFC as well as the feasibility and safety of such a course for long-term improvement in depressive symptoms The proposed study will be conducted over 3 phases Phase I will consist of screening consent and baseline measures Screening will occur under the ETPB screening protocol 01-M-0254 Phase II will consist of a 6-week double-blind sham controlled trial of neuronavigated TMS cognitive therapy Participants will be randomized to two groups receiving either Active or Sham fMRI-guided-TMS while involved in a cognitive therapy session Subjects will participate in 30 daily sessions over 6 weeks with MRI sessions both prior to and immediately after the course of TMS Additionally MEG may optionally be performed at baseline immediately after the first TMSSST session and immediately after the entire course of TMS and an optional battery of TMSEEG excitability and plasticity measures may be performed pre- and post-TMSSST course In Phase III the study team will provide standard of care for depression for up to three months and will prescribe a relapse prevention strategy in consultation with the referring physician including TMS which is consistent with standard of care
Outcome Measures
Primary outcome measures are change in magnitude of BOLD signal recorded in pre- and post-TMS course MRI sessions in the DLPFC region targeted with TMS based on individual activations in that region found at baseline using the priming task and pre- and post-TMS course connectivity changes between DLPFC measured with DTI and resting state functional connectivity and other regions associated with the emotional regulation network specifically OFC medial PFC precuneus and ACC Pre and post TMS course change in depression severity scores HDRS MADRS will also be found in order to look for correlations with these MRI measures Secondary outcome measures will be ratings from the BSL C-SSRS CTQ HAM-A NIH-BFI PANAS RBANS RRS SHAPS and TLEQ as well as electrophysiological changes using MEG and EEG measures
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 17-M-0147 | None | None | None |