We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Transcranial Electrical Stimulation for mTBI (TES for mTBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03244475
Recruitment Status : Not yet recruiting
First Posted : August 9, 2017
Last Update Posted : August 9, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Mild traumatic brain injury (mTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral deficits in OEF/OIF/OND Veterans and the general public. However, the underlying pathophysiology is not completely understood, and there are few effective treatments for post-concussive symptoms (PCS). In addition, there are substantial overlaps between PCS and post-traumatic stress disorder (PTSD) symptoms in mTBI. IASIS is among a class of passive neurofeedback treatments that combine low-intensity pulses for transcranial electrical stimulation (LIP-tES) with electroencephalography (EEG) monitoring. LIP-tES techniques have shown promising results in alleviating PCS individuals with TBI. However, the neural mechanisms underlying the effects of LIP-tES treatment in TBI are unknown, owing to the dearth of neuroimaging investigations of this therapeutic intervention. Conventional neuroimaging techniques such as MRI and CT have limited sensitivity in detecting physiological abnormalities caused by mTBI, or in assessing the efficacy of mTBI treatments. In acute and chronic phases, CT and MRI are typically negative even in mTBI patients with persistent PCS. In contrast, evidence is mounting in support of resting-state magnetoencephalography (rs-MEG) slow-wave source imaging (delta-band, 1-4 Hz) as a marker for neuronal abnormalities in mTBI. The primary goal of the present application is to use rs-MEG to identify the neural underpinnings of behavioral changes associated with IASIS treatment in Veterans with mTBI. Using a double-blind placebo controlled design, the investigators will study changes in abnormal MEG slow-waves before and after IASIS treatment (relative to a 'sham' treatment group) in Veterans with mTBI. In addition, the investigators will examine treatment-related changes in PCS, PTSD symptoms, neuropsychological test performances, and their association with changes in MEG slow-waves. The investigators for the first time will address a fundamental question about the mechanism of slow-waves in brain injury, namely whether slow-wave generation in wakefulness is merely a negative consequence of neuronal injury or if it is a signature of ongoing neuronal rearrangement and healing that occurs at the site of the injury. Specific Aim 1 will detect the loci of injury in Veterans with mTBI and assess the mechanisms underlying functional neuroimaging changes related to IASIS treatment using rs-MEG slow-wave source imaging. The investigators hypothesize that MEG slow-wave source imaging will show significantly higher sensitivity than conventional MRI in identifying the loci of injury on a single-subject basis. The investigators also hypothesize that in wakefulness, slow-wave generation is a signature of ongoing neural rearrangement / healing, rather than a negative consequence of neuronal injury. Furthermore, the investigators hypothesize IASIS will ultimately reduce abnormal MEG slow-wave generation in mTBI by the end of the treatment course, owing to the accomplishment of neural rearrangement / healing. Specific Aim 2 will examine treatment-related changes in PCS and PTSD symptoms in Veterans with mTBI. The investigators hypothesize that compared with the sham group, mTBI Veterans in the IASIS treatment group will show significantly greater decreases in PCS and PTSD symptoms between baseline and post-treatment assessments. Specific Aim 3 will study the relationship among IASIS treatment-related changes in rs-MEG slow-wave imaging, PCS, and neuropsychological measures in Veterans with mTBI. The investigators hypothesize that Reduced MEG slow-wave generation will correlate with reduced total PCS score, individual PCS scores (e.g., sleep disturbance, post-traumatic headache, photophobia, and memory problem symptoms), and improved neuropsychological exam scores between post-IASIS and baseline exams. The success of the proposed research will for the first time confirm that facilitation of slow-wave generation in wakefulness leads to significant therapeutic benefits in mTBI, including an ultimate reduction of abnormal slow-waves accompanied by an improvement in PCS and cognitive functioning.

Condition or disease Intervention/treatment
Mild Traumatic Brain Injury (mTBI) Post-traumatic Stress Disorder Device: IASIS Micro Current Neurofeedback

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 175 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: After consent, Visit 1 (V1) for all three groups will include baseline NP and MHA. Then, baseline rs- MEG and MRI will be performed in V2 for all groups. At V3 the mTBI Veterans in IASIS and sham groups will undergo a pre-session MEG, the first IASIS/Sham treatment Session (S1), and a post-session MEG. Next, the mTBI Veterans continue their IASIS/Sham treatments S2-6 in V4-8. During the mid-treatment V9, another pair of pre- and post-MEG exams and NP will be performed. The mTBI Veterans will continue treatments S8-11 in V10-13. During the final treatment V14, the third pair of pre- and post-MEG exams will be performed. One week after the Veterans finish their final IASIS/Sham treatment S12, a one-week follow-up MEG and NP will be conducted during V15. A subset of IASIS group will be tested one month after the final treatment for a follow-up MEG V16. Veterans initially in the mTBI-sham group will also be offered the real IASIS treatment, but no MEG or behavioral data will be collected.
Masking: Double (Participant, Care Provider)
Masking Description:
Sham treatment, double-blind design: During the sham treatment, we will prep and preplace the electrodes for common reference, A-, B-, plus the set of electrodes on the scalp of the participant following the 10-20 EEG configuration for A+ and A-, just like the procedure for real IASIS treatment. However, no LIP-tES pulses will be sent from the system during sham treatment, based a code entered to the system. A staff member (SRA #1) will assign a mTBI Veteran to either the mTBI-IASIS or the mTBSham group, with an attached code from an existing code bank. Then, the IASIS treatment operator (SRA #2) who is blind to the group assignment will enter the code to the IASIS system during treatments. Based on the code, the system automatically loads the protocol for either IASIS or Sham treatment. Only at the end of the study (after V16), the group assignment is revealed. Therefore, both the participant and IASIS treatment operator (SRA #2) are blind to the group assignment during the study.
Primary Purpose: Treatment
Official Title: Passive Electrical Neurofeedback Treatment of mTBI: MEG and Behavioral Outcomes
Anticipated Study Start Date : October 1, 2017
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2021
Arms and Interventions

Arm Intervention/treatment
Experimental: Neurofeedback
mTBI Veterans blindly assigned to a 6 week IASIS neurofeedback treatment with two sessions per week.
Device: IASIS Micro Current Neurofeedback
The EEG interface device is the J&J Engineering I-330 C2, provided specifically for IASIS. The EEG sampling frequency is 256 Hz on each of 2 EEG acquisition channels. The feedback LIP-tES is delivered via the 4 EEG leads (A+, A-, B+, B-), with respect to the Common Neck Reference (isolated). During each session, 2 electrodes (A- and B-) are attached to the participant's left and right mastoids, while the remaining two electrodes (A+ and B+) are moved to various locations on the scalp to record EEG signals. All four (A+, A-, B+, B-) electrodes are involved in applying weak electric current pulses back to the brain (the feedback process). The feedback signal consists two types of narrow pulse trains, both with 150 mV in amplitude: A Type 1 pulse is 25 ms in duration and contains carrier waves at ~50 KHz. The repetition rate of Type 1 pulse train is fixed at 3.6 Hz; A Type 2 pulse is 120 ns in duration and contains carrier waves at ~100 MHz.
Other Name: LIP-tES intervention
Placebo Comparator: Sham Treatment
mTBI Veterans blindly assigned to a sham treatment for 6 weeks with two sessions per week.
Device: IASIS Micro Current Neurofeedback
The EEG interface device is the J&J Engineering I-330 C2, provided specifically for IASIS. The EEG sampling frequency is 256 Hz on each of 2 EEG acquisition channels. The feedback LIP-tES is delivered via the 4 EEG leads (A+, A-, B+, B-), with respect to the Common Neck Reference (isolated). During each session, 2 electrodes (A- and B-) are attached to the participant's left and right mastoids, while the remaining two electrodes (A+ and B+) are moved to various locations on the scalp to record EEG signals. All four (A+, A-, B+, B-) electrodes are involved in applying weak electric current pulses back to the brain (the feedback process). The feedback signal consists two types of narrow pulse trains, both with 150 mV in amplitude: A Type 1 pulse is 25 ms in duration and contains carrier waves at ~50 KHz. The repetition rate of Type 1 pulse train is fixed at 3.6 Hz; A Type 2 pulse is 120 ns in duration and contains carrier waves at ~100 MHz.
Other Name: LIP-tES intervention
No Intervention: Control
Veterans who are age-, gender-, education-, combat exposure-, and socioeconomically-matched. They will not undergo a treatment.


Outcome Measures

Primary Outcome Measures :
  1. Change in Number of Abnormal MEG Slow-Waves [ Time Frame: Baseline through end of treatment, an average of 6 weeks ]
    We will develop a voxel-wise whole brain MEG source imaging approach for detecting abnormal MEG slow-waves in mTBI Veterans. MEG slow-wave source imaging will be used as an effective clinical tool for assisting in mTBI diagnosis.


Secondary Outcome Measures :
  1. Combat and Post-battle Experiences Scales of the Deployed Risk and Resilience Inventory 2 [ Time Frame: Baseline ]
    At baseline, we will assess combat exposure using the Combat and Post-battle Experiences Scales of the Deployed Risk and Resilience Inventory 2 (DRRI-2), which takes into account the amount level of combat and post-battle exposures, and this coupled with a clinical interview that will detail the amount of times each participant has been exposed to a possible subconcussive blast. In patients with multiple mTBIs, a history of the most recent and all prior mTBIs (life-long) will also be documented for analyzing the effects of repetitive mTBI on MEG slow-wave source imaging. In patients with multiple TBIs, both old and new injuries may contribute to the generation of abnormal MEG slow-waves.

  2. Ohio State University Traumatic Brain injury Identification method (OSU TBI-ID) [ Time Frame: Baseline ]
    Lifetime history of TBI will be assessed using the Ohio State University Traumatic Brain injury Identification method (OSU TBI-ID).

  3. Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Up to 6 weeks ]
    Since sleep is often disrupted in mTBI, the Pittsburgh Sleep Quality Index (PSQI) will be given to assess for 7 different components of sleep: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medications and daytime dysfunction over the last month.

  4. The McGill Pain Questionnaire (MGPQ) [ Time Frame: Up to 6 weeks ]
    The McGill Pain Questionnaire (MGPQ) will evaluate the level of current pain, pain changes over time, and strength of pain, since pain is frequently co-morbid with mTBI.

  5. Mini- International Neuropsychiatric Interview (MINI-7) [ Time Frame: Baseline ]
    At baseline, Veterans in all three groups will be evaluated by a psychologist under the supervision of Co-I, Dr. Baker, using a structured clinical interview, the Mini- International Neuropsychiatric Interview (MINI-7) to rule in/out mental health disorders.

  6. Clinician-Administered PTSD Scale (CAPS-5) [ Time Frame: Up to 6 weeks ]
    The Clinician- Administered PTSD Scale (CAPS-5) for DSM-5. The CAPS-5 is a standard semi-structured interview used to assess PTSD diagnosis and severity. As part of as a structured interview, the primary traumatic event is elicited and will be used as the basis of assessing PTSD symptoms. The CAPS-5 total symptom severity score is calculated by summing severity scores for the DSM-5 PTSD symptoms that are assessed with this 30 item questionnaire. PTSD diagnostic status will be assessed using the past month version of the CAPS-5. The CAPS-5 has the advantages of categorical (diagnostic) or dimensional scoring of PTSD plus items for assessing social and occupational functioning, dissociation, and the validity of the items. A total severity score of 33 or higher indicates full threshold PTSD. The CAPS-5 past week version quantitative data will be given prior to treatment and at follow-up (Visit 15) and used for evaluation of treatment (IASIS or sham) and for correlation with MEG data.

  7. Post-Concussion Check List (PCL-5) [ Time Frame: Up to 6 weeks ]
    PCL-5 will also be given to track changes in PTSD symptoms.

  8. Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) [ Time Frame: Baseline ]
    We will utilize Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to assess alcohol and substance use over the lifetime and frequency of past 3 months.

  9. Alcohol Use Disorders Identification Test (AUDIT) [ Time Frame: Baseline ]
    Alcohol Use Disorders Identification Test (AUDIT) will assess alcohol abuse problems.

  10. California Verbal Learning Test-2nd Edition [ Time Frame: Up to 6 weeks ]
    We will use scaled scores from verbal learning and retrospective memory (California Verbal Learning Test-2nd Edition).

  11. Wechsler Adult Intelligence Scale-4th Edition (WAIS-IV) [ Time Frame: Up to 6 weeks ]
    We will use scaled scores from the WAIS-IV Symbol Search and Coding subtests to compare processing speed. The Digit Span subtest will assess attention and working memory.

  12. Delis-Kaplan Executive Function System (DKEFS) [ Time Frame: Up to 6 weeks ]
    We will use scaled scores from the DKEFS Verbal Fluency, Trail-Making, and Color-Word Interference subtests to assess executive functioning.

  13. Connors Continuous Performance Task II (CPT-II) [ Time Frame: Up to 6 weeks ]
    The Connors Continuous Performance Task II (CPT-II) will be included as a measure of attention and impulsivity.

  14. Barratt Impulsivity Scale [ Time Frame: Up to 6 weeks ]
    Impulsivity will also be measured by Barratt Impulsivity Scale a self-report questionnaire.

  15. Frontal Systems Behavior Scale [ Time Frame: Baseline ]
    Since frontal lobe areas are more prone to damage, the Frontal Systems Behavior Scale will measure behavioral dysfunction associated with frontal subcortical impairment.

  16. Wechsler Test of Adult Reading [ Time Frame: Baseline ]
    The Wechsler Test of Adult Reading will provide an estimate of premorbid ability.

  17. Test of Memory Malingering (TOMM) [ Time Frame: Baseline ]
    Effort will be assessed using the Test of Memory Malingering (TOMM).

  18. CogState Ltd [ Time Frame: Up to 6 weeks ]
    In order to measure change at multiple time points, we will administer the Detection, Identification, and Two-back tests from CogState Ltd, a tablet-administered battery optimized with multiple versions for use in clinical trials.

  19. Conventional MRI T1-weighted 3D-IRSPGR pulse sequence [ Time Frame: Baseline ]
    Conventional MRI T1-weighted images will be used to construct a source grid for Fast VESTAL and a boundary element method (BEM) model for MEG forward calculation.

  20. Susceptibility-weighted MRI [ Time Frame: Baseline ]
    Susceptibility-weighted imaging will also be performed to detect subtle blood products.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion of Veterans for the mTBI groups:

  • All symptomatic mTBI patients will be evaluated in a clinical interview to document the nature of the injuries and ongoing PCS.
  • The diagnosis of mTBI patients is based on standard VA/DOD diagnostic criteria.
  • Inclusion in the mTBI patient group requires a TBI that meets the following criteria:

    • a loss of consciousness (LOC) < 30 minutes or transient confusion, disorientation, or impaired consciousness immediately after the trauma
    • post-traumatic amnesia (PTA) < 24 hours
    • an initial Glasgow Coma Scale (GCS) [90] between 13-15 (if available)
  • Since the GCS assessment is often not available in theater, Veterans with missing GCS, but who meet other inclusion criteria will also be recruited.
  • Each patient must have at least 3 items of persistent PCS at the beginning of the study.

Inclusion of Healthy Control (HC) group:

  • Veterans that qualify as HCs will be age, education, combat exposure, and socioeconomically matched to the mTBI groups.
  • In addition to exclusion criteria listed above, HC subjects must not have been diagnosed with head injury, affective disorder, or PTSD (CAPS-5 < 8) throughout life.

Exclusion Criteria:

  • Exclusion criteria for study participations include:
  • history of other neurological, developmental, or psychiatric disorders (based on the DSM-5 (MINI-7) [86] structured interview), e.g.,:

    • brain tumor
    • stroke
    • epilepsy
    • Alzheimer's disease
    • schizophrenia
    • bipolar disorder
    • ADHD
    • or other chronic neurovascular diseases such as hypertension and diabetes
  • substance or alcohol use disorders according to DSM-5 [87] criteria within the six months prior to the study
  • history of metabolic or other diseases known to affect the central nervous system (see [88] for similar criteria)
  • Metal objects (e.g., shrapnel or metal fragments) that fail MRI screening, or extensive metal dental hardware, e.g.,:

    • braces and large metal dentures

      • fillings are acceptable
    • other metal objects in the head
    • neck, or face areas that cause non-removable artifacts in the MEG data
  • Potential subjects will be administered the Beck Depression Inventory (BDI-II) to evaluate level of depressive symptoms, and suicidal ideation

    • any participant who reports a "2" or "3" on the BDI-II: item 9 (suicidal thoughts or wishes) will also be excluded.
    • However, depression following mTBI or traumatic event of PTSD is common [89]: therefore, in two mTBI groups, the investigators will include and match patients with depression symptoms reported after their injury/event, and will co-vary BDI-II score in data analyses.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03244475


Contacts
Contact: Annemarie A Quinto, BA (858) 822-2352 adangeles@ucsd.edu
Contact: Ashley R Swan, BA (858) 822-6874 arobb@ucsd.edu

Locations
United States, California
VA San Diego Healthcare System, San Diego, CA Recruiting
San Diego, California, United States, 92161
Contact: Annemarie A Quinto, BA    858-822-2352    adangeles@ucsd.edu   
Contact: Ashley R Swan, BA    (858) 822-6874    arobb@ucsd.edu   
Principal Investigator: Mingxiong Huang, PhD         
Sponsors and Collaborators
VA Office of Research and Development
San Diego Veterans Healthcare System
Investigators
Principal Investigator: Mingxiong Huang, PhD VA San Diego Healthcare System, San Diego, CA
More Information

Publications:

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03244475     History of Changes
Other Study ID Numbers: B1988-I
RX001988-01A1 ( Other Grant/Funding Number: Office of Research and Development )
First Posted: August 9, 2017    Key Record Dates
Last Update Posted: August 9, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

One or more data sets without personal identifiers will be generated during the data analysis phase of this study. Publications from this research will be made available to the public through the National Library of Medicine PubMed Central website within one year after the date of publication. The data sets will include all data underlying any publications generated by this study and therefore, these will be sufficient to reproduce or verify any published findings.

Requests for access to final data sets must be made in writing signed by a requestor from the United States and include an email address for delivery and an assurance that the recipient will not attempt to identify or re-identify any individual. The request should reference the publication underlying the request. Requests may be made to the PI/lead point-of-contact for the publication. If the investigator leaves the VASDHS the requests may be sent to the Associate Chief of Staff for Research.

URL: http://

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
mild Traumatic Brain Injury
transcranial electrical stimulation
neurofeedback
magnetoencephalography
post-traumatic stress disorder

Additional relevant MeSH terms:
Brain Injuries
Stress Disorders, Traumatic
Brain Injuries, Traumatic
Stress Disorders, Post-Traumatic
Brain Concussion
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Trauma and Stressor Related Disorders
Mental Disorders
Head Injuries, Closed
Wounds, Nonpenetrating