Frontal iTBS for Impulsivity and Suicidal Ideation in Veterans With Mild Traumatic Brain Injury

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VA Office of Research and Development

Status and phase

Not yet enrolling
Phase 1

Conditions

Suicidal Ideation
Mild Traumatic Brain Injury
Impulsivity

Treatments

Device: placebo intermittent theta burst stimulation
Device: intermittent theta burst stimulation

Study type

Interventional

Funder types

Other U.S. Federal agency

Identifiers

NCT05647044
D4298-W

Details and patient eligibility

About

The investigators hope to develop a treatment for suicidal ideation (SI), impulsivity and functional impairments (such as difficulties in social and work settings) that occur after a mild traumatic brain injury (mTBI). These conditions have been shown to be linked. The investigators are using a high-powered magnetic pulse, called intermittent theta burst stimulation (iTBS) applied to the head to see if it can improve these symptoms. The high-powered magnetic pulse causes certain cells in the brain to activate, which seems to strengthen connections between parts of the brain. The purpose of this research is to gather early information on the safety and effectiveness of iTBS provided to the front of the head for impulsivity, SI and functional deficits after mTBI. The investigators plan to use the data collected in this study to develop larger studies in the future. iTBS is FDA approved, but not for these specific symptoms, or in the specific location the investigators are placing it. The investigators are testing to see if its effective for the above conditions when applied to the front of the head.

Full description

Individuals with mild traumatic brain injury (mTBI) are at increased risk of dying by suicide compared to those without - both among Veteran and civilian populations. 22% of Veterans with mTBI report struggling with suicidal ideation (SI). Despite this, there are no effective evidence-based treatments for co-occurring mTBI and SI. Deficits in social and occupational functioning, which often follow mTBI, are strongly related to suicidal ideation (SI) and improvements in these areas are known to lessen SI. Thus, improving function for those with mTBI and SI is of great potential significance. The impulsivity that Veterans with mTBI exhibit is referred to as "negative urgency impulsivity". It often involves aggressive and self-harming behaviors, which impede societal re-integration and rehabilitation. Prior studies indicate negative urgency impulsivity is: (1) a common TBI sequela and (2) a risk factor for SI. Previous studies have also indicated individuals with TBI, SI and negative urgency impulsivity had reduced right-sided ventromedial prefrontal cortex (VMPFC) volume compared to Veterans without these conditions. The VMPFC plays a key role in controlling impulsive limbic responses. These findings are consistent with published reports suggesting individuals with reduced VMPFC volume are more likely to (a) have SI and (b) behave impulsively. Transcranial magnetic stimulation (TMS) holds significant therapeutic promise for post-mTBI SI, impulsivity and functional deficits. TMS induces neuroplasticity, leading to changes that have the potential to improve neurorehabilitation outcomes. TMS is effective for treating post-TBI depression when administered to the dorsolateral prefrontal cortex. Intermittent theta burst stimulation (iTBS) is a "second generation" form of TMS that is delivered more rapidly. It has been proposed that frontal pole TMS could directly strengthen connections throughout the prefrontal cortex, including the VMPFC, thereby dampening limbic system activity. Such a TMS treatment strategy could be used to treat post-mTBI impulsivity and SI, ultimately allowing Veterans to regain functioning. It is not know which Veterans would benefit most from this treatment; examining neural connectivity changes before and after iTBS could determine who would respond to frontal pole iTBS and why. The investigators will conduct a randomized, double-blinded frontal iTBS pilot clinical trial for Veterans with mTBI, impulsivity and SI. As this is a novel treatment approach for this population, this project will focus on testing the safety, feasibility and tolerability of frontal pole iTBS. To inform future research, this project will determine the preliminary effects of iTBS on functioning, negative urgency impulsivity and SI among the pilot sample. This project will also inform future research by examining the relationships between the functional neural connectivity of the VMPFC to the limbic system and how this is affected by iTBS using resting state functional connectivity (rsFC) neuroimaging data, pre- and post-iTBS.

Enrollment

55 estimated patients

Sex

All

Ages

22 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • 22-65 years of age
  • can read and speak English
  • meets criteria for mTBI according to the symptom attribution and classification (SACA) scale
  • Has a C-SSRS (suicidal ideation rating) of >1 within the past month
  • Has a history of impulsivity documented in the medical chart and/or a score of >20 on the UPPS-P negative urgency impulsivity subscale

Exclusion criteria

  • Has contraindications to iTBS (i.e., epilepsy)
  • Has contraindications to MRI (i.e., claustrophobia, ferromagnetic metal implants)
  • Has an active substance use disorder per the DSM-V criteria
  • Has a history of moderate to severe TBI
  • Has a history of non-traumatic neuroinjury (i.e., stroke, neurosurgery, hemorrhage)
  • Has a history of, or current psychosis not due to an external cause
  • Is pregnant
  • Has an active, unstable medical condition
  • Is within 12 weeks of a major surgery or operation
  • Is within 1 year of TBI

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

55 participants in 2 patient groups, including a placebo group

active iTBS
Active Comparator group
Description:
Subjects receiving active iTBS treatment
Treatment:
Device: intermittent theta burst stimulation
placebo iTBS
Placebo Comparator group
Description:
Subjects receiving placebo (sham) iTBS treatment
Treatment:
Device: placebo intermittent theta burst stimulation

Trial contacts and locations

1

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Central trial contact

Alexandra L Aaronson, MD; Ibuola Kale

Data sourced from clinicaltrials.gov

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