Ignite Creation Date:
2024-05-06 @ 8:27 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06389266
Status:
RECRUITING
Last Update Posted:
2024-04-29
First Post:
2024-04-24
Brief Title:
Network-Targeted Neuromodulation for Nicotine Dependence in Schizophrenia
Sponsor:
Vanderbilt University Medical Center
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
Network-Targeted Neuromodulation for Nicotine Dependence in Schizophrenia
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 goal of this clinical trial is to compare two active types of transcranial magnetic stimulation in two nicotine-using populations nicotine-using people with psychosis and nicotine-using people without a diagnosis of a psychotic disorder The main questions it aims to answer are
1 Can rTMS change functional connectivity in brain circuits associated with nicotine use
2 Are those rTMS-induced changes in functional connectivity related to craving
Participants will complete tasks assessing their cognitive performance and craving before and after each week of TMS Researchers will compare the effect of each TMS intervention on participants with and without psychosis to see if one type of TMS has an effect on nicotine craving
1 Can rTMS change functional connectivity in brain circuits associated with nicotine use
2 Are those rTMS-induced changes in functional connectivity related to craving
Participants will complete tasks assessing their cognitive performance and craving before and after each week of TMS Researchers will compare the effect of each TMS intervention on participants with and without psychosis to see if one type of TMS has an effect on nicotine craving
Detailed Description:
This study proposes to test the hypothesis that the brain circuits most relevant to nicotine use in schizophrenia are distinct from pathways identified in nicotine-using people without psychosis This study seeks to provide evidence that targeted stimulation of the Default Mode Network DMN leads to both altered network activity and a concomitant behavioral change in cue-induced craving and cognitive performance in individuals with schizophrenia and schizoaffective disorder while targeted stimulation of the left dorsolateral prefrontal cortex L DLPFC leads to these changes in nicotine-using people without psychosis
We will test this hypothesis in a crossover design comparing 1 DMN-targeted continuous theta burst stimulation cTBS and 2 L DLPFC-targeted intermittent theta burst stimulation iTBS cTBS and iTBS are types of rTMS cTBS has inhibitory effects and reduces functional connectivity while iTBS is excitatory and increases connectivity Huang et al 2005 By applying cTBS to the DMN a target that modulates craving in schizophrenia we expect DMN connectivity to decrease thereby decreasing craving Excitatory stimulation eg iTBS to the L DLPFC reduces craving in smokers without psychosis Tseng et al 2022
This study will test a model that integrates brain network pathophysiology and cognition to 1 explain the prevalence of nicotine use in schizophrenia and 2 identify a target for engagement in schizophrenia This study seeks to establish a neuroscientific framework to guide future treatment-oriented studies aimed at reducing craving and improving cognitive performance in individuals with schizophrenia and schizoaffective disorder
Aim 1 Target Engagement Determine if rTMS manipulates functional connectivity of each target DMN L DLPFC n60 Hypothesis 1A Functional connectivity of the entire DMN will decrease after 5 days of DMN-targeted cTBS Hypothesis 1B Functional connectivity of the L DLPFC to the left insula will increase after 5 days of L DLPFC-targeted iTBS As an exploratory hypothesis we will test if there is an effect of diagnosis on connectivity change
Aim 2 Clinical Efficacy Determine if rTMS affects cue-induced craving and if craving change correlates with change in functional connectivity n60 Hypothesis 2A Both DMN-targeted and L DLPFC-targeted rTMS will significantly reduce craving Hypothesis 2B Craving change will be correlated with functional connectivity change As an exploratory hypothesis in individuals with schizophrenia DMN-targeted cTBS will be more efficacious than L DLPFC-targeted iTBS
Aim 3 Determine if individual differences in rTMS-induced network connectivity change are explained by individual differences in network controllability n60 There is significant heterogeneity in individual response to rTMS even with network-targeted approaches This may be related to network controllability a metric of the average input energy required to change brain state Bassett and Sporns 2017 It is critical to understand predictors of network change for optimal rTMS target selection in clinical trials Hypothesis 3 Individual differences in rTMS-induced change in DMN connectivity will be associated with average controllability of the DMN rTMS stimulation site
We will test this hypothesis in a crossover design comparing 1 DMN-targeted continuous theta burst stimulation cTBS and 2 L DLPFC-targeted intermittent theta burst stimulation iTBS cTBS and iTBS are types of rTMS cTBS has inhibitory effects and reduces functional connectivity while iTBS is excitatory and increases connectivity Huang et al 2005 By applying cTBS to the DMN a target that modulates craving in schizophrenia we expect DMN connectivity to decrease thereby decreasing craving Excitatory stimulation eg iTBS to the L DLPFC reduces craving in smokers without psychosis Tseng et al 2022
This study will test a model that integrates brain network pathophysiology and cognition to 1 explain the prevalence of nicotine use in schizophrenia and 2 identify a target for engagement in schizophrenia This study seeks to establish a neuroscientific framework to guide future treatment-oriented studies aimed at reducing craving and improving cognitive performance in individuals with schizophrenia and schizoaffective disorder
Aim 1 Target Engagement Determine if rTMS manipulates functional connectivity of each target DMN L DLPFC n60 Hypothesis 1A Functional connectivity of the entire DMN will decrease after 5 days of DMN-targeted cTBS Hypothesis 1B Functional connectivity of the L DLPFC to the left insula will increase after 5 days of L DLPFC-targeted iTBS As an exploratory hypothesis we will test if there is an effect of diagnosis on connectivity change
Aim 2 Clinical Efficacy Determine if rTMS affects cue-induced craving and if craving change correlates with change in functional connectivity n60 Hypothesis 2A Both DMN-targeted and L DLPFC-targeted rTMS will significantly reduce craving Hypothesis 2B Craving change will be correlated with functional connectivity change As an exploratory hypothesis in individuals with schizophrenia DMN-targeted cTBS will be more efficacious than L DLPFC-targeted iTBS
Aim 3 Determine if individual differences in rTMS-induced network connectivity change are explained by individual differences in network controllability n60 There is significant heterogeneity in individual response to rTMS even with network-targeted approaches This may be related to network controllability a metric of the average input energy required to change brain state Bassett and Sporns 2017 It is critical to understand predictors of network change for optimal rTMS target selection in clinical trials Hypothesis 3 Individual differences in rTMS-induced change in DMN connectivity will be associated with average controllability of the DMN rTMS stimulation site
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None