Mild TBI Assessment & Rehabilitation (MTAR)

Multi-Level Assessment and Rehabilitation of Combat Mild TBI

One of the most pressing concerns within the VA currently is the provision of interventions that address the cognitive as well as emotional problems faced by Veterans with mild TBI and comorbid conditions. When completed, these studies will inform us whether training core attentional self-regulatory control functions via personally-relevant activities will be effective in improving daily life for Veterans with mild TBI and comorbid conditions. The study design will provide a test not only of potential benefits for real life functioning, but also determine to what extent these benefits are related to actual changes in cognitive/behavioral performance and brain networks corresponding to these functions. This project will provide a foundation for future studies to investigate the neural mechanisms that support improvements of cognition and behavior in mTBI.

Study Overview

• Status: Recruiting
• Conditions: Brain Injuries, Traumatic
• Intervention / Treatment: Behavioral: Goal-Oriented Attentional Self-Regulation (GOALS); Device: fMRI; Other: Brain Health Education (BHE)

Detailed Description

Combat-related mild traumatic brain injury (mTBI) and co-morbid conditions are prevalent in returning Veterans with the reported rates ranging from 14- 22%. Chronic sequela of mTBI can be highly debilitating due to deficits in the cognitive control processes, including attention, executive functions, and memory. In prior studies, individuals with chronic acquired brain injury who participated in a cognitive training program, Goal-Oriented Attentional Self-Regulation (GOALS), which targets executive control functions of applied mindfulness-based attention regulation and goal management, improved cognitive performance in areas of: complex attention/executive function and memory, complex functional task performance, and daily functioning. Furthermore, functional MRI (fMRI) results after training indicated significantly enhanced modulation of neural processing. Preliminary data from recently completed randomized-control GOALS study in 32 Veterans with chronic TBI also show both short and longer term (up to 2 years) improvements in attention and executive function, complex real-life tasks, and emotional regulation.

The primary objectives of this study are to investigate the potential short and longer term effects of GOALS cognitive training program, and to use advanced MRI to investigate changes in brain structure and function in the circuits that regulate attention, memory, executive function and emotion in Veterans with chronic mTBI.

The investigators postulate that 1) GOALS training will improve neurocognitive function in attention and executive function domains, complex functional task performance, and emotional regulation in Veterans with chronic mTBI; 2) improved neurocognitive function will be correlated with macrostructural, microstructural and functional changes in the corresponding brain networks on high field (3T) and ultra-high field (7T) structural MR imaging, diffusion tensor imaging (DTI) and resting state fMRI performed pre- and post-training; 3) Changes in both behavioral function and imaging measures will be maintained at 6 months post-training and be associated with improvements in activities and participation.

AIM 1: To determine the short and long term effects of GOALS training on neuro-cognitive performance and neural plasticity of attention and executive control networks in mTBI.

AIM 2: To determine the short and long term effects of GOALS training on complex functional task performance and daily functioning, and on plasticity in pathways related to memory function, in mTBI.

AIM 3: To determine the short and long term effects of GOALS training on measures of emotional regulation, and on plasticity of frontolimbic networks related to emotion processing, in mTBI In a randomized, controlled interventional study design, 36 Veterans with a history of chronic (> 6 month) mTBI and residual cognitive difficulties will be randomized to participate in 5 weeks of cognitive training (GOALS) or a treatment as usual (TAU) comparison. At baseline, week 5 (post GOALS), and at 6 months, participants will undergo a multi-level assessment battery consisting of: 1) neuroimaging with high field (3T) and ultra-high field (7T) structural MR imaging, diffusion tensor imaging (DTI) and resting state fMRI; 2) neuropsychological assessment focusing on complex attention and executive function; 3) complex 'real life' functional task performance; and 4) self-report measures of daily functioning and emotional regulation/health.

Additionally, the investigators will be recruiting a separate cohort of 15 equally matched healthy veteran volunteers who have no TBI history, for normative comparisons. TBI-negative participants, who will not be participating in training sessions, will have neuroimaging with ultra-high field (7T) structural MR imaging and neuropsychological assessments at baseline and week 5.

When completed, this project will determine whether training core attentional self-regulatory control functions via personally-relevant activities will be effective in improving quality of life and daily functioning for Veterans with mTBI. The study design will provide a test of potential benefits on real-life functioning, and also determine to what extent these benefits are related to actual changes in hypothetically targeted cognitive/behavioral functions and brain networks corresponding to these functions.

Overall recruitment status was changed due to a new study site being added at UCSF. This was made possible by funding recently received from private donation through UCSF's Weill Institute for Neuroscience to study a cohort recruited via physician referral at UCSF.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pratik Mukherjee, MD PhD; Phone Number: (415) 353-9364; Email: pratik.mukherjee@ucsf.edu
• Study Contact Backup: Name: Tatjana Novakovic-Agopian, PhD; Phone Number: (415) 753-3888; Email: tatjana.novakovic-agopian@va.gov

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California, San Francisco
      • Contact: Pratik Mukherjee, MD; Phone Number: 23852 415-353-8972; Email: pratik.mukherjee@ucsf.edu
      • Contact: Tatjana Novakovic-Agopian; Phone Number: 4157533888; Email: Tatjana.Novakovic-agopian@ucsf.edu
    • San Francisco, California, United States, 94121-1563
      • Completed
      • San Francisco VA Medical Center, San Francisco, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For TBI-positive veteran participants, to be randomized to either GOALS or TAU:

• Ages 18+
• A history of mild TBI (as defined by DOD / VA; confirmed by medical records and in person Ohio State University TBI Instrument)
• Chronic, stable phase of recovery (>6 months from last post-concussive event)
• Report of residual cognitive difficulties (1 moderate or severe cognitive symptom(s) on the Neurobehavioral Symptom Inventory (NSI)) that interfere(s) with daily function
• Able and willing to commit to participate in training and assessments
• If on psychoactive medications, must be stable on medications (> 30 days)

For the TBI-negative healthy veteran control group:

• Ages 18+
• No history of any (mild to severe) TBI (as defined by DOD / VA; confirmed by medical records and in person Ohio State University TBI Instrument)
• Able and willing to commit to participate in assessments
• If on psychoactive medications, must be stable on medications (> 30 days)

Exclusion Criteria:

For the TBI-positive veteran participants, to be randomized to either GOALS or TAU:

• A history of moderate or severe TBI
• Unstable medical, neurologic, or psychiatric condition, including severe cognitive dysfunction, or other reasons for being unable or unwilling to participate in study procedures (e.g., contraindications to MRI)
• Ongoing illicit drug or alcohol abuse (AUDIT>8)
• Psychosis
• Severe depression, anxiety or PTSD that precludes participation in research activities
• Poor English comprehension
• Eligible participants may have other co-morbid stable neuropsychiatric disorders, including depression and PTSD
• There will be no restriction in regard to gender, race and socioeconomic status

For the TBI-negative healthy veteran control group:

• A history of any mild, moderate, or severe TBI
• Unstable medical, neurologic, or psychiatric condition, including severe cognitive dysfunction, or other reasons for being unable or unwilling to participate in study procedures (e.g. contraindications to MRI)
• Ongoing illicit drug or alcohol abuse (AUDIT>8)
• Psychosis
• Severe depression, anxiety or PTSD that precludes participation in research activities
• Poor English comprehension
• Eligible participants may have other co-morbid stable neuropscyhiatric disorders, including depression and PTSD.
• There will be no restriction in regard to gender, race and socioeconomic status

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Veteran Mild TBI Group - GOALS Intervention; Veterans ages 18+ with chronic mild TBI, to undergo GOALS cognitive training as an intervention.	Behavioral: Goal-Oriented Attentional Self-Regulation (GOALS); GOALS is a manualized, therapist-administered cognitive training program that targets executive control functions of applied mindfulness-based attention regulation and goal management strategies and links them to participant-defined real-life goals. In contrast to training via practice on isolated tasks, this training protocol involves application of attention regulation skills and strategies to participant-defined goals in real life, ecologically valid settings. One of the main training aims is to improve self-regulatory control mechanisms as they contribute to goal attainment.; Device: fMRI; Functional Magnetic Resonance Imaging of the Brain
Active Comparator: Veteran Mild TBI - Treatment as Usual; Veterans ages 18+ with chronic mild TBI, matched by demographic and clinical criteria to the GOALS group, to receive the standard clinical care.	Device: fMRI; Functional Magnetic Resonance Imaging of the Brain; Other: Brain Health Education (BHE); BHE group is a formal in-person, active, psycho-educational, control intervention closely matched to GOALS for length, intensity, and contact with a therapist/facilitator. Topics include brain structure, function, sleep, stress, emotion and the brain.; Other Names: Treatment As Usual (TAU)
No Intervention: Veteran Non TBI - No Treatment; Veterans ages 18+ with no history of TBI, to undergo Neuropsychologic evaluation and MR Imaging with no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delis-Kaplan Executive Function System (D-KEFS) Stroop Inhibition-Switching Task	Single Test for Attention, Executive Function and Mental Flexibility	6 months after enrollment

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Pratik Mukherjee, MD PhD, San Francisco VA Medical Center, San Francisco, CA

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2017
• Primary Completion (Estimated): June 12, 2024
• Study Completion (Estimated): December 13, 2024

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: September 28, 2016
• First Posted (Estimated): September 30, 2016

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Rehabilitation; Functional Magnetic Resonance Imaging
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: N2300-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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