High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for Sensory Deficits in Complex Traumatic Brain Injury (NAVIGATE-TBI)

Aim 1: To use magnetoencephalography (MEG) and magnetic resonance imaging (MRI) in Veterans and civilians with mild traumatic brain injury (mTBI) and sensory postconcussive symptoms (PCS) to demonstrate the mechanism of therapeutic benefit of HD-tDCS for sensory symptoms, as shown by reliable changes in the activity of the cognitive control network (CCN) and sensory system network (SSN) following stimulation; Aim 2: this intervention will result in long-term improvements in measures of executive function, depression/anxiety, and quality of life.

Study Overview

• Status: Completed
• Conditions: Mild Traumatic Brain Injury
• Intervention / Treatment: Device: Active High-definition transcranial direct current stimulation (HD-tDCS); Device: Sham High-definition transcranial direct current stimulation (HD-tDCS)

Detailed Description

Experimental Design and Methods Participants: 120 subjects will be recruited for this study from the NM VA Health Care System and community, 40 healthy controls subjects for an imaging-only group, and 80 mTBI subjects for the stimulation arm who have suffered injury at least 3 months prior to study enrollment, but not more than 15 years prior to enrollment. All participants will be 18-59 years of age.

Recruitment: Human participants (ages 18-59) will be invited to come to the University of New Mexico (UNM) to ask questions prior to providing consent. They will be provided with consent forms that describe the study procedures and potential risks.

Once informed consent is obtained and the appropriate forms signed, the participant will be assigned a unique research subject identifier (URSI) number, and from that point forward all research data will only be labeled with the URSI number. The key linking identifiers of participants to the URSI will be maintained on a separate database that will be stored behind locked doors, in a locked filing cabinet in a secure area. All participants may then undergo demographic data collection, neuropsychological assessments sensory evaluation, at UNM. They may also undergo MEG and MRI at the Mind Research Network (MRN), located in the same building.

Demographic Data: As part of the initial assessment, basic demographic data regarding the subject may be noted down, including age, gender, socioeconomic status, educational attainment, handedness, use of common stimulants such as caffeine, and brain injury severity. They may also be asked if they are willing to allow their medical record to be accessed, for the purposes of confirming details about any traumatic brain injury (TBI) as well as obtaining results of neuroimaging studies done at the time of injury or afterward. This will include medical, surgical, neurological and psychiatric history, results of lab tests, brain scans, electroencephalography tests, medication lists, information from doctor's visits and hospital visits.

Neuropsychological testing procedures: All neuropsychological testing will be administered in the Center for Brain Recovery and Repair Core by trained study personnel under direct supervision of core directors. The following domains and tests will be administered: Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (Examiner); Digit Span; Delis-Kaplan Executive Function Systems (DKEFS) Trail-making Test Conditions 2 and 4; Hopkins Verbal Learning Test (HVLT); Frontal Systems Behavior Scale (FrSBe); Test of Memory Malingering (TOMM); Wechsler Test of Adult Reading (WTAR); Digit Symbol Coding; Handedness; Socioeconomic Status (SES); Patient's Global Impression of Change (PGIC); Glasgow Outcome Scale-Extended (GOSE).

Sensory Assessment: Hearing, balance, and vision will be assessed using Common Data Element (CDE) instruments, including the Hearing Handicap Assessment, the Test for Visual Discomfort, the modified Balance Error Scoring System. Oculomotor control will be assessed using virtual reality goggles (Oculus) with implanted eye trackers (iScan).

Magnetoencephalography: Magnetoencephalography (MEG) may be done after neuropsychological testing. The participant will sit in the MEG scanner to record brain magnetic fields. MEG setup takes between 10 and 30 minutes, and subsequent recording takes one hour. During MEG assessments participants will complete numerous tasks. Each task is designed to parse different cognitive mechanisms that contribute to sensory performance. In perceptual tasks, participants will discriminate tone pitches amongst novel distracting tones (Auditory Orienting Task; AOT). For eye movement tasks, participants are asked look either towards or away from a visual stimulus (Pro- and Anti-saccades).

Magnetic resonance imaging (MRI): MRI scan(s) will be obtained for integration with MEG, as needed for analyses. Total scan time, including participant setup and removal, is expected to take 1 hour. Participants may lie down on a table and be placed into a long donut-shaped magnet. During the scan, participants will be asked to rest quietly or to fixate on a dot on a screen in front of them, or to perform a memory task. No contrast will be used. Any female over 18 who thinks she may be pregnant will complete a urine pregnancy screen before the MRI scan.

Following initial testing, the participants in the stimulation arm of the study will receive 10 consecutive weekday sessions of high-definition transcranial direct current stimulation. 2 milliamperes active or sham anodal current will be delivered to the left dorsolateral prefrontal cortex for 30 minutes. During this time, participants will perform vision therapy tasks through a virtual reality headset, or a computer-based working memory task. Skin sensations will be assessed every 10 minutes.

Post stimulation testing: the next available weekday following completion of the study protocol, subjects will return to UNM to repeat the demographic, neuropsychological, sensory, and imaging assessments.

Long term followup: At 1 month, 3 months and 6 months after stimulation, subjects will be contacted via telephone or meet in person, and will be administered the Beck Depression Inventory (BDI-II), Posttraumatic Stress Disorder Checklist-Military (PCL-M), the Neurobehavioral Symptom Inventory (NSI), and Patient Global Impression of Change (PGIC) quality of life assessment tools utilized before and immediately after, after stimulation. Veterans will undergo these study followup visits at NMVAHCS, and civilians at UNM.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. are US Veteran or Active Duty Military personnel aged 18-59,
2. have suffered a mild TBI (alteration in neurological functioning < 24 hours, loss of consciousness (LOC) less than 30 minutes, Glasgow coma scale (GCS) score (if available) of between 13 and 15 acutely, and less than 24 hours of post-traumatic amnesia (PTA));
3. were injured between 3 months and 15 years ago;
4. have post-traumatic sensory symptoms as evidenced by endorsing at least 2 out of 12 sensory symptoms on the Neurobehavioral Symptom Inventory (NSI), a measure of post-traumatic symptoms from the NIH Common Data Elements (CDE) to a severity of "3" or higher,
5. are fluent in English,
6. have been on stable doses of any psychotropic medications for the past 2 months.
7. The imaging-only group will have the same inclusion and exclusion criteria except they will not have had a head injury.

Exclusion Criteria:

1. any history of moderate or severe TBI;
2. a prior history of other neurological disease or any history of seizures beyond immediate post-traumatic seizure, to as to reduce risk of exacerbation of epilepsy or other neurological symptoms;
3. history of psychosis, so as to reduce risk of psychiatric decompensation;
4. history of current or recent (within two years) substance/alcohol dependence, to reduce confounding effects on cognition and plasticity;
5. any discontinuity in skull electrical conductivity (i.e., unhealed burr holes in scalp) or artificially constructed (metal or plastic) craniotomy cover, to reduce risk of unimpeded electrical current;
6. presence of any implanted electrical device (e.g. pacemaker), to reduce risk of device malfunction;
7. recent medical hospitalization (within three weeks), to reduce risk of medical decompensation during the study;
8. any condition that would prevent the subject from completing the protocol; 9) appointment of a legal representative, as assessed via direct inquiry of the subject and a designated trusted other, to avoid coercion of a vulnerable population;

10) any significant blindness, to screen out peripheral sensory damage; 11) any significant deafness beyond mild hearing loss, to screen out peripheral sensory damage; 12) any ongoing litigation related to TBI, to prevent interference with legal proceedings; 13) any contraindication to MRI; 14) membership in an identified vulnerable population, including minors, pregnant women, and prisoners, so as to prevent coercion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Stimulation; Active HD-tDCS will be delivered while subjects perform sensory training tasks.	Device: Active High-definition transcranial direct current stimulation (HD-tDCS); Active HD-tDCS delivers active current through 2-10 electrodes held against the scalp with a lycra cap at specified 10-20 electroencephalography (EEG) coordinates.
Sham Comparator: Sham Stimulation; Sham HD-tDCS will be delivered while subjects perform sensory training tasks.	Device: Sham High-definition transcranial direct current stimulation (HD-tDCS); Sham HD-tDCS delivers sham current through 2-10 electrodes held against the scalp with a lycra cap at specified 10-20 electroencephalography (EEG) coordinates
No Intervention: Imaging Only; 40 subjects will undergo initial testing only as a healthy control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postconcussive sensory symptoms	Somatic sub scale score from the Neurobehavioral Symptom Inventory (NSI) (range 0-48; 0-12 mild; 13-24 moderate; 25-36 severe; 37-48 very severe)	2 week visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetoencephalography peak activation	Peak activation during the Auditory Orienting Task (AOT) performed during magnetoencephalography	2 week visit

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: University of Miami; The City College of New York; The Mind Research Network; New Jersey Institute of Technology; Biomedical Research Institute of New Mexico

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2018
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: CDMRP-PT160096

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data, including demographic, neuropsychological, and imaging data, will be uploaded to FITBIR for use by TBI researchers, as specified by the grant sponsor.
• IPD Sharing Time Frame: Data will be uploaded to the Federal Interagency Traumatic Brain Injury Registry (FITBIR) at study termination.

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