rTMS Target Identification for Functional Disability in AUD+mTBI (rTMS-TARGET-ID)

February 21, 2024 updated by: VA Office of Research and Development

Neural Target Identification for Functional Disability Associated With Alcohol Related Characteristics Among Veterans With Co-occurring Alcohol Use Disorder and Traumatic Brain Injury

The objectives of this VA Merit application are to identify a neural target unique to Veterans with co-occurring alcohol use disorder and mild traumatic brain injury (AUD+mTBI) and to test the efficacy of this target as a stimulation site for repetitive transcranial magnetic stimulation (rTMS) treatment to maximize functional recovery. rTMS will soon be a treatment option at 30 VAs nationwide and preliminary studies show promise for AUD and mTBI treatment. A better understanding of how AUD+mTBI impacts the brain needs to occur in order to advance rTMS to optimize function. This research is aligned with the VA RR&D's mission to generate knowledge and innovations to advance the rehabilitative health and care of Veterans, to effectively integrate clinical and applied rehabilitation research, and translate research results into practice. This research is also aligned with the goal of the Psychological Health & Social Reintegration portfolio to develop interventions improving psychological health status of Veterans enabling them to function more fully in society.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Alcohol use disorder (AUD) and mild traumatic brain injury (mTBI) impact functional abilities. AUD occurs in up to 35% of Veterans with mTBI. Evidence suggests that co-occurrence of AUD and mTBI (AUD+mTBI) leads to an exacerbation of brain dysfunction, symptom manifestation, and ultimately, functional disability. Alcohol-related characteristics are operationally defined per AUD symptoms and outcomes including, but not limited to, alcohol consumption, alcohol craving, and AUD severity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory treatment that will soon be a treatment option at 30 VAs nationwide. Preliminary rTMS efficacy is demonstrated for AUD alone and mTBI alone using a variety of neural targets. rTMS is, thus, a promising treatment for AUD+mTBI. The objectives of this study are to 1) identify neural targets (i.e. site of stimulation) associated with both alcohol-related characteristics and self-reported functional disability, and 2) assess preliminary efficacy and sustainability of a high frequency rTMS protocol applied to these customized neural targets relative to the commonly used left dorsolateral prefrontal cortex (DLPFC) site. Addressing these objectives are essential steps towards the long-term research goal [to customize and clinically implement a rTMS treatment] that can improve brain function resulting in optimal recovery for Veterans with AUD+mTBI. To address the first study objective, Veterans will be recruited and classified into one of two groups based on structured-interviews, self-report measures, and neuropsychological assessments: 1) AUD+mTBI, and 2) [Veteran controls] without a history or symptoms of mTBI or AUD. Alcohol-related characteristics will be assessed through objective measures of alcohol use, self-report measures, and structured interviews. Self-reported functional disability will be assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS). Neuroimaging metrics will be assessed through a multi-modal, functional and structural Magnetic Resonance Imaging (MRI) scan. Participants will complete a functional MRI (fMRI) protocol where brain activation will be measured in response to viewing images related to alcohol, compared to neutral images. Advanced neuroimaging procedures to determine the structural integrity of white matter fibers in the brain and spontaneous activity in brain networks, a process called resting state functional connectivity (rsFC), will also be conducted. To address the second study objective, AUD+mTBI Veterans will receive rTMS at one site randomly assigned from a set of 4 sites: 3 customized neural targets identified in this study, and the commonly used left DLPFC. AUD+mTBI Veterans will complete 10 PLACEBO, then 10 ACTIVE rTMS sessions in a within-subjects design. Follow-up WHODAS assessments will occur at 2-weeks, 1-month and 6-months post-ACTIVE rTMS. Aim 1 will identify unique neural targets for rTMS to treat AUD+mTBI by determining which multi-modal neuroimaging metrics are most strongly associated with both alcohol-related characteristics and functional disability. Aim 2 will [test preliminary efficacy of high-frequency rTMS administered over the customized neural targets] to treat functional disability among Veterans with AUD+mTBI. Aim 3 will assess sustainability of rTMS effects on functional disability for Veterans with AUD+mTBI. The investigators hypothesize that for Veterans with AUD+mTBI, there are neural substrates of AUD related to functional disability, and that neuromodulation of these substrates will be related to gains in functional disability. The investigators' innovative approach represents an advancement in the field of neurorehabilitation because a neural target will be systematically defined, using multi-modal neuroimaging, prior to preliminary rTMS efficacy and sustainability testing. These steps are necessary to customize rTMS treatment for a population of Veterans with co-occurring conditions and unique health care needs. Thus, the outcomes of this research will optimize function for Veterans with AUD+mTBI.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Hines, Illinois, United States, 60141-3030
        • Recruiting
        • Edward Hines Jr. VA Hospital, Hines, IL
        • Contact:
        • Contact:
        • Principal Investigator:
          • Amy A Herrold, PhD BA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Can read and speak English
  • Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for AUD
  • Symptom Attribution and Classification (SACA) criteria (Pape, Herrold et al 2016, JHTR) for mTBI (without requirement of clinical neuropsychological impairment)

Exclusion Criteria:

  • History of moderate to severe TBI
  • Neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis)
  • History of or current psychotic spectrum disorders (i.e., schizophrenia, schizoaffective and bipolar disorders)
  • Intellectual disability (WTAR predicted full-scale IQ score < 70)42
  • Are pregnant or nursing
  • Use of benzodiazepines, opiates, cocaine, or amphetamines in the past 30 days
  • Meet DSM-5 criteria for moderate to severe cannabis use disorder
  • Contraindications to MRI (e.g., claustrophobia, ferromagnetic metal in eyes or face, congestive heart failure, implanted cardiac pacemaker or defibrillator, cochlear implant, nerve stimulator)
  • Meet SACA criteria for 'Questionable Validity' of performance effort and symptom reporting

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active + Placebo rTMS for Custom Neural Target Group 1
Custom neural anatomical target 1 defined by neuroimaging data
Device: Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P
rTMS device
Other Names:
  • rTMS device
Active Comparator: Active + Placebo rTMS for Custom Neural Target Group 2
Custom neural anatomical target 2 defined by neuroimaging data
Device: Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P
rTMS device
Other Names:
  • rTMS device
Active Comparator: Active + Placebo rTMS for Custom Neural Target Group 3
Custom neural anatomical target 3 defined by neuroimaging data
Device: Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P
rTMS device
Other Names:
  • rTMS device
Active Comparator: Active + Placebo rTMS for Left DLPFC Neural Target
Neural anatomical target will be the Left Dorsolateral Prefrontal Cortex identified using the 5cm from the motor "hot spot" rule.
Device: Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P
rTMS device
Other Names:
  • rTMS device

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
World Health Organization Disability Assessment Schedule 2.0 (WHODAS) Change
Time Frame: baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 6 months
36-item self report measure of global functional disability. We will use the complex scoring method which creates a summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Amy A Herrold, PhD BA, Edward Hines Jr. VA Hospital, Hines, IL

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2019

Primary Completion (Estimated)

May 31, 2025

Study Completion (Estimated)

May 31, 2025

Study Registration Dates

First Submitted

July 31, 2019

First Submitted That Met QC Criteria

July 31, 2019

First Posted (Actual)

August 2, 2019

Study Record Updates

Last Update Posted (Estimated)

February 22, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D2916-R
  • I01RX002916 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

A de-identified, anonymized dataset will be created and shared. MRI images will anonymized and made available through the Northwestern University Neuroimaging Data Archive (NUNDA). Final data sets will be made available as per Hines VA Hospital local policy for long term storage and access until enterprise-level resources become available. These data will be available upon request by researchers and scientists in accordance with federal guidelines and Hines local policy.The data provided will be sufficient for anyone to perform analogous or supplemental analyses that would permit validation of the analysis and results. The sharing of data will enable others to evaluate the data and to validate and interpret the data independently. In order to insure that replication is possible and transparency, statistical code complementary to datasets will be made available through the Federal Interagency Traumatic Brain Injury Research Informatics System.

IPD Sharing Time Frame

Three years after study completion or after all primary papers have been accepted for publication.

IPD Sharing Access Criteria

Federal Interagency Traumatic Brain Injury Research Informatics System.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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