Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial

BackgroundSuicide remains a leading cause of death among veterans in the United States, and mild traumatic brain injury (mTBI) increases the risk of suicidal ideation (SI) and suicide attempts (SAs). mTBI worsens impulsivity and contributes to poor social and occupational fun...

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Main Authors: Alyssa Bernanke, Rebecca Hasley, Niki Sabetfakhri, Harriet de Wit, Bridget M Smith, Lei Wang, Lisa A Brenner, Colleen Hanlon, Noah S Philip, Olusola Ajilore, Amy Herrold, Alexandra Aaronson
Format: Article
Language:English
Published: JMIR Publications 2024-12-01
Series:JMIR Research Protocols
Online Access:https://www.researchprotocols.org/2024/1/e58206
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author Alyssa Bernanke
Rebecca Hasley
Niki Sabetfakhri
Harriet de Wit
Bridget M Smith
Lei Wang
Lisa A Brenner
Colleen Hanlon
Noah S Philip
Olusola Ajilore
Amy Herrold
Alexandra Aaronson
author_facet Alyssa Bernanke
Rebecca Hasley
Niki Sabetfakhri
Harriet de Wit
Bridget M Smith
Lei Wang
Lisa A Brenner
Colleen Hanlon
Noah S Philip
Olusola Ajilore
Amy Herrold
Alexandra Aaronson
author_sort Alyssa Bernanke
collection DOAJ
description BackgroundSuicide remains a leading cause of death among veterans in the United States, and mild traumatic brain injury (mTBI) increases the risk of suicidal ideation (SI) and suicide attempts (SAs). mTBI worsens impulsivity and contributes to poor social and occupational functioning, which further increases the risk of SI and SAs. Repetitive transcranial magnetic stimulation is a neuromodulatory treatment approach that induces neuroplasticity, potentially repairing neurodamage. Intermittent theta burst stimulation (iTBS) is a second-generation form of transcranial magnetic stimulation that is safe, shorter in duration, displays a minimal side effect profile and is a promising treatment approach for impulsivity in mTBI. Our novel proposed treatment protocol uses frontal pole iTBS to target the ventromedial prefrontal cortex, which may reduce impulsivity by strengthening functional connectivity between the limbic system and frontal cortex, allowing for improved top-down control of impulsive reactions, including SI and SAs. ObjectiveThe objectives of this study are to (1) develop an iTBS intervention for veterans with mTBI, impulsivity, and SI; (2) assess the feasibility and tolerability of the intervention; and (3) gather preliminary clinical outcome data on SI, impulsivity, and functions that will guide future studies. MethodsThis is a pilot, double-blinded, randomized controlled trial. In developing this protocol, we referenced the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. We will enroll 56 participants (28 active iTBS and 28 sham iTBS). The iTBS intervention will be performed daily, 5 days a week, for 2 weeks. We will collect 10 validated, psychometric, quantitative outcome measures before, during, and after the intervention. Measures included will assess functioning, impulsivity, suicidality, posttraumatic stress disorder, and depressive symptoms. We will collect qualitative data through semistructured interviews to elicit feedback on the participants’ experiences and symptoms. We will perform quantitative and qualitative analyses to (1) assess the feasibility, tolerability, and acceptability of the treatment; (2) gather advanced neuroimaging data to assess neural changes elicited by treatment; and (3) assess improvements in outcome measures of impulsivity and suicidality in veterans with mTBI. ResultsThis study protocol was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board (Hines IRB number 14-003). This novel treatment is a 5-year research project (April 1, 2023, to March 31, 2028) funded by the Veterans Administration Rehabilitation Research and Development service (CDA2 award IK2 RX002938). Study results will be disseminated at or before the project’s end date in March 2028. ConclusionsWe will provide preliminary evidence of the safety, feasibility, and acceptability of a novel frontal pole iTBS treatment for mTBI, impulsivity, SI and SAs, and functional deficits. Trial RegistrationClinicalTrials.gov NCT05647044; https://clinicaltrials.gov/study/NCT05647044 International Registered Report Identifier (IRRID)PRR1-10.2196/58206
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spelling doaj-art-872486583e42425282d6437489c71f332025-08-20T02:50:37ZengJMIR PublicationsJMIR Research Protocols1929-07482024-12-0113e5820610.2196/58206Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled TrialAlyssa Bernankehttps://orcid.org/0009-0000-9036-717XRebecca Hasleyhttps://orcid.org/0009-0000-4373-4221Niki Sabetfakhrihttps://orcid.org/0000-0002-5062-5661Harriet de Withttps://orcid.org/0000-0002-7211-8994Bridget M Smithhttps://orcid.org/0000-0002-3301-8843Lei Wanghttps://orcid.org/0000-0003-3870-3388Lisa A Brennerhttps://orcid.org/0000-0002-2629-214XColleen Hanlonhttps://orcid.org/0000-0002-3151-0279Noah S Philiphttps://orcid.org/0000-0002-4889-8775Olusola Ajilorehttps://orcid.org/0000-0003-0737-0437Amy Herroldhttps://orcid.org/0000-0001-5675-4053Alexandra Aaronsonhttps://orcid.org/0000-0001-9015-2240 BackgroundSuicide remains a leading cause of death among veterans in the United States, and mild traumatic brain injury (mTBI) increases the risk of suicidal ideation (SI) and suicide attempts (SAs). mTBI worsens impulsivity and contributes to poor social and occupational functioning, which further increases the risk of SI and SAs. Repetitive transcranial magnetic stimulation is a neuromodulatory treatment approach that induces neuroplasticity, potentially repairing neurodamage. Intermittent theta burst stimulation (iTBS) is a second-generation form of transcranial magnetic stimulation that is safe, shorter in duration, displays a minimal side effect profile and is a promising treatment approach for impulsivity in mTBI. Our novel proposed treatment protocol uses frontal pole iTBS to target the ventromedial prefrontal cortex, which may reduce impulsivity by strengthening functional connectivity between the limbic system and frontal cortex, allowing for improved top-down control of impulsive reactions, including SI and SAs. ObjectiveThe objectives of this study are to (1) develop an iTBS intervention for veterans with mTBI, impulsivity, and SI; (2) assess the feasibility and tolerability of the intervention; and (3) gather preliminary clinical outcome data on SI, impulsivity, and functions that will guide future studies. MethodsThis is a pilot, double-blinded, randomized controlled trial. In developing this protocol, we referenced the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. We will enroll 56 participants (28 active iTBS and 28 sham iTBS). The iTBS intervention will be performed daily, 5 days a week, for 2 weeks. We will collect 10 validated, psychometric, quantitative outcome measures before, during, and after the intervention. Measures included will assess functioning, impulsivity, suicidality, posttraumatic stress disorder, and depressive symptoms. We will collect qualitative data through semistructured interviews to elicit feedback on the participants’ experiences and symptoms. We will perform quantitative and qualitative analyses to (1) assess the feasibility, tolerability, and acceptability of the treatment; (2) gather advanced neuroimaging data to assess neural changes elicited by treatment; and (3) assess improvements in outcome measures of impulsivity and suicidality in veterans with mTBI. ResultsThis study protocol was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board (Hines IRB number 14-003). This novel treatment is a 5-year research project (April 1, 2023, to March 31, 2028) funded by the Veterans Administration Rehabilitation Research and Development service (CDA2 award IK2 RX002938). Study results will be disseminated at or before the project’s end date in March 2028. ConclusionsWe will provide preliminary evidence of the safety, feasibility, and acceptability of a novel frontal pole iTBS treatment for mTBI, impulsivity, SI and SAs, and functional deficits. Trial RegistrationClinicalTrials.gov NCT05647044; https://clinicaltrials.gov/study/NCT05647044 International Registered Report Identifier (IRRID)PRR1-10.2196/58206https://www.researchprotocols.org/2024/1/e58206
spellingShingle Alyssa Bernanke
Rebecca Hasley
Niki Sabetfakhri
Harriet de Wit
Bridget M Smith
Lei Wang
Lisa A Brenner
Colleen Hanlon
Noah S Philip
Olusola Ajilore
Amy Herrold
Alexandra Aaronson
Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial
JMIR Research Protocols
title Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial
title_full Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial
title_fullStr Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial
title_full_unstemmed Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial
title_short Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial
title_sort frontal pole neuromodulation for impulsivity and suicidality in veterans with mild traumatic brain injury and common co occurring mental health conditions protocol for a pilot randomized controlled trial
url https://www.researchprotocols.org/2024/1/e58206
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