Mild Traumatic Brain Injury (mTBI)TESmTBINCT03244475
Transcranial Electrical Stimulation for mTBI
A study testing TES in people with Mild Traumatic Brain Injury (mTBI) and Post-traumatic Stress Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Traumatic Brain Injury (mTBI), Post-traumatic Stress Disorder
- What is being tested?
- TES
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2017to 30 Sep 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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.
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161
About this study
Official title: Passive Electrical Neurofeedback Treatment of mTBI: MEG and Behavioral Outcomes
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 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 EEG monitoring. Nexalin is another tES technique , with FDA approvals for treating insomnia, depression, and anxiety. 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. For a subset of participants who may have remaining TBI symptoms at the end of all IASIS treatment sessions, MEG slow-wave changes will be recorded before and after additional Nexalin treatment. 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.
Read the detailed description
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. Furthermore, a substantial number of studies have shown higher (nearly double) rates of comorbid PTSD in individuals with mTBI, observed in military and civilian settings. IASIS is among a class of passive neurofeedback treatments that combine low-intensity pulses for transcranial electrical stimulation (LIP-tES) with electroencephalography (EEG) monitoring. Nexalin is another tES technique , with FDA approvals for treating insomnia, depression, and anxiety. LIP-tES techniques have shown promising results in alleviating PCS in 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 as a non-invasive imaging marker for neuronal abnormalities in mTBI. Using region of interest (ROI) and voxel-wise approaches, the investigators demonstrated that MEG slowwave source imaging detects abnormal slow-waves (delta-band, 1-4 Hz) with ~85% sensitivity in chronic and sub-acute mTBI patients with persistent PCS. 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 slowwaves before and after IASIS treatment (relative to a 'sham' treatment group), and for a subset, before and after additional Nexalin treatment, 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. Pre-treatment baseline and posttreatment rs-MEG exams, symptoms assessments, and neuropsychological tests will be performed. 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: To detect the loci of injury in Veterans with mTBI and assess the mechanisms underlying functional neuroimaging changes related to IASIS treatment, and for a subset of Veterans with remaining symptoms, additional Nexalin treatment, using rs-MEG slow-wave source imaging. The investigators' voxel-wise rs-MEG source-imaging technique will be used to identify abnormal slow-wave generation (delta band) in the baseline and post-treatment MEG exams to assess treatment-related changes on a single-subject basis. Healthy control (HC) Veterans, matched for combat exposure, will be used to establish an MEG normative database. Test-retest reliability of MEG slow-wave source imaging for mTBI will also be examined.
Hypothesis 1: Veterans with mTBI will generate abnormal MEG slow-waves during the baseline MEG exam. Voxel-wise 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 test-retest reliability of MEG slow-wave source imaging is expected to be high, with intra-class correlation coefficient (ICC) 0.75 between two sequential MEG exams.
Hypothesis 2: In wakefulness, slow-wave generation is a signature of ongoing neural rearrangement/ healing, rather than a negative consequence of neuronal injury. IASIS treatment will enhance neural rearrangement/healing by initially potentiating slow-wave generation immediately after each treatment session.
Hypothesis 3: 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. In Veterans with mTBI who finish IASIS treatment, but not in the sham group, MEG source imaging will show a significant decrease in abnormal slow-waves at post-treatment exam. Such significant decreases will also be evident in both the voxel-wise and overall abnormal MEG slow-wave measures.
Specific Aim 2: To examine treatment-related changes in PCS and PTSD symptoms in Veterans with mTBI. PCS and PTSD symptoms will be assessed at the baseline and post-treatment follow-up visits.
Hypothesis 4: Compared with the sham group, mTBI Veterans in the IASIS treatment group will show significantly greater decreases in PCS symptoms between baseline and post-treatment assessments.
Hypothesis 5: Compared with the sham group, mTBI Veterans in the IASIS treatment group will also show significantly greater decreases in PTSD symptoms between baseline and post-treatment assessments.
Specific Aim 3: To study the relationship among IASIS treatment-related changes in rs-MEG slow-wave imaging, PCS, and neuropsychological measures in Veterans with mTBI. The investigators will correlate changes between baseline and post-IASIS abnormal rs-MEG slow-wave generation (i.e., total abnormal rs-MEG slow-wave and voxel-wise source imaging measures) with changes in PCS and neuropsychological tests performance.
Hypothesis 6: 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.
- Being tested
- TES
- Keywords
- mild Traumatic Brain Injury, transcranial electrical stimulation, neurofeedback, magnetoencephalography, post-traumatic stress disorder
- Medical subject headings
- Brain Concussion, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TESDevice
Also called LIP-tES intervention
The EEG interface device is the J\&J Engineering I-330 C2. IASIS is delivered via the 4 EEG leads with respect to the Common Neck Reference. During each session, 2 electrodes are attached to the participant's left and right mastoids, while the remaining 2 electrodes are moved to various locations on the scalp to record EEG signals. All 4 electrodes are involved in applying weak electric current pulses back to the brain. The feedback signal consists 2 types of narrow pulse trains, both with 150mV in amplitude.
The Nexalin device, FDA clearance (501K=K024377, Classification: Stimulator, Cranial Electrotherapy: CFR 882. 5800: U.S. Patent #6904322B2), produces a waveform that provides tES to the brain delivered at a frequency of 4Hz, 40Hz, and 77.5Hz at 0 to 15mA peak current. Evidence shows this waveform, at these frequencies, results in improved clinical outcomes for anxiety and pain. We hypothesize that repeated TES treatments serve to stimulate long-term neurochemical changes.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Electrical Stimulation (TES) | Experimental | mTBI Veterans blindly assigned to a 6 week of TES, either IASIS neurofeedback treatment or Nexalin, with 2-3 sessions per week. Receives: Device: TES |
| Sham Treatment | Placebo comparator | mTBI Veterans blindly assigned to a sham treatment for 6 weeks with 2-3 sessions per week. Receives: Device: TES |
| Control | No intervention | Veterans who are age-, gender-, education-, combat exposure-, and socioeconomically-matched. They will not undergo a treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Abnormal Magnetoencephalography (MEG) Slow-Waves (1-4 Hz) Activity
We will develop a voxel-wise whole brain MEG source imaging approach for detecting abnormal Magnetoencephalography (MEG) slow-waves (1-4 Hz) in mTBI Veterans. The unit of the abnormal MEG source activity was measured in pico Ampere-meter (or pA-m which is 10^(-12) A-m). Natural logarithm transformation (i.e., e-based) was used. So, the unit of the MEG source imaging was log(pA-m). The range of the voxel-wise MEG source activity scale is 0-10. High amplitude of the MEG source activity suggests more serious injury. In the present study, we measured the Difference score in MEG exam pre- vs post the transcranial electrical stimulation (TES) treatment. Our primary measure is the reduction of the abnormal MEG source activity for slow waves (1-4 Hz), defined as the MEG activity at the pre-TES exam minus that at the post-TES exam. So, the higher this difference score is, the better outcomes due to the TES treatment in reducing the abnormal MEG signal.
Measured: Baseline through end of treatment, an average of 6 weeks
Rivermead Post Concussion Symptom Questionnaire
The Rivermead Post Concussion Symptom Questionnaire (RPQ) total score was used to assess change in post-concussion symptoms due to TES. Our focus in this analysis was the difference score in RPQ total score pre- vs post-treatment measures.
The questionnaire has 16 items and uses scale of 0 - 4, with 0 as "not experienced at all" and 4 as "a severe problem." Value range: 0 - 64, where the higher scores mean a worse outcome.
For this measure, we focused on the difference score: total score from prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
Measured: Baseline through end of treatment, an average of 6 weeks
Neurobehavioral Symptoms Inventory
The Neurobehavioral Symptoms Inventory (NSI) total score was used to assess the changes of post-concussion symptoms due to TES. Our focus in this analysis was the difference score in NSI total score pre- vs post-treatment measures.
The NSI has 22 items and uses a response scale of 0 - 4, with 0 as "none" and 4 as "very severe." Value range: 0 - 88, where the higher scores mean a worse outcome/more severe post-concussive symptoms.
For this measure, we focused on the difference score: total score from prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
Measured: Baseline through end of treatment, an average of 6 weeks
Secondary outcomes (9)
The McGill Pain Questionnaire (MGPQ)
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.
Category scores range from 1-2 through 1-6. Minimum score = 0. Maximum score = 78. The higher the pain score, the greater the pain.
For this measure, we focused on the difference score: total score from prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
Measured: Baseline through end of treatment, an average of 6 weeks
Clinician-Administered PTSD Scale (CAPS-5)
The CAPS-5 is a standard semi-structured interview used to assess PTSD diagnosis and severity. The primary traumatic event is elicited and will be used as the basis of assessing PTSD symptoms. The total symptom severity score is calculated by summing severity scores assessed in this 30-item questionnaire. PTSD diagnostic status will be assessed using the past month version of the CAPS-5A, in which total severity score of 33 or higher indicates full threshold PTSD. The past week version of the CAPS-5 will be given prior to treatment and at follow-up.
Severity scores range on a response scale of 0-5, 0=absent, 5=extreme/incapacitating. CAPS-55 summary scores range from 0 to 80, with the higher scores indicating greater severity of PTSD symptoms.
For this measure, we focused on the difference score: total score from prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
Measured: Up to 6 weeks
Post-Concussion Check List (PCL-5)
PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The PCL-5 uses a response scale of 0 - 4. 0 = "Not at all" to 4 = "Extremely." The total score can range from 0 - 80, with the higher the score corresponding to a higher level of distress to the very stressful experience. The difference between scores post-treatment and pre-treatment will analyzed in addition to the CAPS-5 (1 week version) outcomes. DSM-5 symptom cluster severity scores can be obtained by summing the scores for the items within a given cluster, i.e., cluster B (items 1-5), cluster C (items 6-7), cluster D (items 8-14), and cluster E (items 15-20); these subscale scores may be used in secondary analysis.
Measured: Up to 6 weeks
California Verbal Learning Test-2nd Edition - Free Recall Total Correct T-score
We will use T-scores from verbal learning and retrospective memory (California Verbal Learning Test-2nd Edition). Alternate CVLT forms were used during the post-treatment session.
T-score ranges from 5 to 95, where the higher the T-score, the better the outcome. The T-score indicates the number of standard deviations away from the mean, where 50 is the mean with a standard deviation of 10, and is age- and gender-corrected.
Analysis was based on the difference score between pre-treatment and post-treatment Free Recall Total Correct T-score. The lower the difference score, the more positive change was observed.
Measured: Up to 6 weeks
Wechsler Adult Intelligence Scale-4th Edition (WAIS-IV) Processing Speed Index
We will use the sum of scaled scores from the WAIS-IV Symbol Search and Coding subtests to attain the Processing Speed Index.
PSI ranged from 50 - 150, where the higher the score, the better the outcome. Analysis was based on the difference score between pre-treatment Processing Speed Index and post-treatment Processing Speed Index. The lower the difference score, the more positive change was observed.
Measured: Up to 6 weeks
Delis-Kaplan Executive Function System (DKEFS) - Trail Number/Letter Switching Scaled
Throughout the study, we used DKEFS Verbal Fluency, Trail-Making, and Color-Word Interference subtests to assess executive functioning.
Analysis was based on the DKEFS Trailmaking Number/Letter Switching scaled score. Scaled scores range from 1-19, where the higher the scaled score, the better the outcome.
Analysis was based on the difference score between pre-treatment scaled score and the post-treatment scaled score. The lower the difference score, the more positive change was observed.
Measured: Up to 6 weeks
Connors Continuous Performance Task II (CPT-II) - Inattention Omissions T-Score
The Connors Continuous Performance Task II (CPT-II) was included as a measure of attention and impulsivity.
In this measure, converted T-scores represent the score of the individual relative to the population, who are of the same gender and same age group. A T-score of 50 represents the average for the comparison group. T-score ranges from under 40 (very good performance) to 65+ (markedly atypical). The higher the scores, the worse the performance.
This analysis focused on the difference score between the Inattention Omissions T-score pre- and post-treatment. The higher the difference score, the more positive change was observed.
Measured: Up to 6 weeks
Barratt Impulsivity Scale
Impulsivity was also measured by Barratt Impulsivity Scale, a self-report questionnaire.
This scale contains 30 items, with total scores that range from 30 - 120. The higher the score, the worse the outcome.
Analysis was based on the difference score between pre- and post-treatment. The higher the difference score, the more positive change was observed.
Measured: Up to 6 weeks
Frontal Systems Behavior Scale
Since frontal lobe areas are more prone to damage, the Frontal Systems Behavior Scale (FrSBe) will measure behavioral dysfunction associated with frontal subcortical impairment.
FrSBe is a 46-item rating scale with three subscales: Apathy (14 items), Disinhibition (15 items), and Executive Function (17 items). Items are rated in a 5-point scale, where higher scores mean a worse outcome. The raw scores of these subscales were converted to T-scores, with range of 9 - >/= 140, where T-scores greater than 65 are considered clinically significant.
For this measure, we focused on the difference score of the total T-score prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
Measured: Baseline through end of treatment, an average of 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2017
- Study start1 Feb 2017
- Primary completion30 Sep 2022
- Study completion30 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Mild Traumatic Brain Injury (mTBI)Studies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After consent, Visit 1 (V1) for all 3 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 TES and sham groups will undergo a pre-session MEG, the first TES/Sham treatment Session (S1), and a post-session MEG. Next, the mTBI Veterans continue their TES/Sham treatments S2-6 in V4-8. During V9, a pair of pre- and post-MEG exams and NP will be performed. The mTBI Veterans will continue treatments S8-11 in V10-13. During V14, a pair of pre- and post-MEG exams will be performed. 1 week after the Veterans finish their final TES/Sham treatment S12, a 1-week follow-up MEG and NP will be conducted during V15. A subset of TES group will be tested 1 month after the final treatment for a follow-up MEG V16. Veterans in the mTBI-sham group will be offered the real TES treatment.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- San Diego Veterans Healthcare System
- Responsible party
- Sponsor
- Investigators
- Mingxiong Huang, PhD, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03244475
- Sponsor's protocol ID
- B1988-I
- Other IDs
- RX001988-01A1
- Acronym
- TESmTBI
- Status last verified
- Dec 2023
- First submitted
- 24 Jul 2017
- Last updated
- 18 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: 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.
Publications
Huang MX, Nichols S, Baker DG, Robb A, Angeles A, Yurgil KA, Drake A, Levy M, Song T, McLay R, Theilmann RJ, Diwakar M, Risbrough VB, Ji Z, Huang CW, Chang DG, Harrington DL, Muzzatti L, Canive JM, Christopher Edgar J, Chen YH, Lee RR. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury. Neuroimage Clin. 2014 Jun 16;5:109-19. doi: 10.1016/j.nicl.2014.06.004. eCollection 2014.
PubMed 25009772Huang M, Risling M, Baker DG. The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury. Psychoneuroendocrinology. 2016 Jan;63:398-409. doi: 10.1016/j.psyneuen.2015.02.008. Epub 2015 Feb 23.
PubMed 25769625Robb Swan A, Nichols S, Drake A, Angeles A, Diwakar M, Song T, Lee RR, Huang MX. Magnetoencephalography Slow-Wave Detection in Patients with Mild Traumatic Brain Injury and Ongoing Symptoms Correlated with Long-Term Neuropsychological Outcome. J Neurotrauma. 2015 Oct 1;32(19):1510-21. doi: 10.1089/neu.2014.3654. Epub 2015 Jun 18.
PubMed 25808909MacGregor AJ, Dougherty AL, Galarneau MR. Injury-specific correlates of combat-related traumatic brain injury in Operation Iraqi Freedom. J Head Trauma Rehabil. 2011 Jul-Aug;26(4):312-8. doi: 10.1097/HTR.0b013e3181e94404.
PubMed 20808241MacDonald CL, Johnson AM, Nelson EC, Werner NJ, Fang R, Flaherty SF, Brody DL. Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel. J Neurotrauma. 2014 May 15;31(10):889-98. doi: 10.1089/neu.2013.3173. Epub 2014 Feb 10.
PubMed 24367929Hoffman SW, Harrison C. The interaction between psychological health and traumatic brain injury: a neuroscience perspective. Clin Neuropsychol. 2009 Nov;23(8):1400-15. doi: 10.1080/13854040903369433.
PubMed 19882478Vasterling JJ, Brailey K, Proctor SP, Kane R, Heeren T, Franz M. Neuropsychological outcomes of mild traumatic brain injury, post-traumatic stress disorder and depression in Iraq-deployed US Army soldiers. Br J Psychiatry. 2012 Sep;201(3):186-92. doi: 10.1192/bjp.bp.111.096461. Epub 2012 Jun 28.
PubMed 22743844Nelson DV, Esty ML. Neurotherapy of Traumatic Brain Injury/Post-Traumatic Stress Symptoms in Vietnam Veterans. Mil Med. 2015 Oct;180(10):e1111-4. doi: 10.7205/MILMED-D-14-00696.
PubMed 26444476Schoenberger NE, Shif SC, Esty ML, Ochs L, Matheis RJ. Flexyx Neurotherapy System in the treatment of traumatic brain injury: an initial evaluation. J Head Trauma Rehabil. 2001 Jun;16(3):260-74. doi: 10.1097/00001199-200106000-00005.
PubMed 11346448Huang MX, Nichols S, Robb A, Angeles A, Drake A, Holland M, Asmussen S, D'Andrea J, Chun W, Levy M, Cui L, Song T, Baker DG, Hammer P, McLay R, Theilmann RJ, Coimbra R, Diwakar M, Boyd C, Neff J, Liu TT, Webb-Murphy J, Farinpour R, Cheung C, Harrington DL, Heister D, Lee RR. An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes. Neuroimage. 2012 Jul 16;61(4):1067-82. doi: 10.1016/j.neuroimage.2012.04.029. Epub 2012 Apr 20.
PubMed 22542638Huang MX, Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J, Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D, Coimbra R, Lee RR. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.
PubMed 19385722Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S, Orrison WW. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55. doi: 10.1097/01.HTR.0000271115.29954.27.
PubMed 17510590Lewine JD, Davis JT, Sloan JH, Kodituwakku PW, Orrison WW Jr. Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. AJNR Am J Neuroradiol. 1999 May;20(5):857-66.
PubMed 10369357
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Passive Electrical Neurofeedback Treatment of mTBI: MEG and Behavioral Outcomes
- ClinicalTrials.gov ID
- NCT03244475
- Acronym / sponsor ID
- TESmTBI / B1988-I
- Keywords
- mild Traumatic Brain Injury, transcranial electrical stimulation, neurofeedback, magnetoencephalography, post-traumatic stress disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- San Diego Veterans Healthcare System
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 9 Aug 2017 (actual)
- Results
- Posted 18 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 EEG monitoring. Nexalin is another tES technique , with FDA approvals for treating insomnia, depression, and anxiety. 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. For a subset of participants who may have remaining TBI symptoms at the end of all IASIS treatment sessions, MEG slow-wave changes will be recorded before and after additional Nexalin treatment. 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.
Detailed description
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. Furthermore, a substantial number of studies have shown higher (nearly double) rates of comorbid PTSD in individuals with mTBI, observed in military and civilian settings. IASIS is among a class of passive neurofeedback treatments that combine low-intensity pulses for transcranial electrical stimulation (LIP-tES) with electroencephalography (EEG) monitoring. Nexalin is another tES technique , with FDA approvals for treating insomnia, depression, and anxiety. LIP-tES techniques have shown promising results in alleviating PCS in 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 as a non-invasive imaging marker for neuronal abnormalities in mTBI. Using region of interest (ROI) and voxel-wise approaches, the investigators demonstrated that MEG slowwave source imaging detects abnormal slow-waves (delta-band, 1-4 Hz) with ~85% sensitivity in chronic and sub-acute mTBI patients with persistent PCS. 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 slowwaves before and after IASIS treatment (relative to a 'sham' treatment group), and for a subset, before and after additional Nexalin treatment, 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. Pre-treatment baseline and posttreatment rs-MEG exams, symptoms assessments, and neuropsychological tests will be performed. 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: To detect the loci of injury in Veterans with mTBI and assess the mechanisms underlying functional neuroimaging changes related to IASIS treatment, and for a subset of Veterans with remaining symptoms, additional Nexalin treatment, using rs-MEG slow-wave source imaging. The investigators' voxel-wise rs-MEG source-imaging technique will be used to identify abnormal slow-wave generation (delta band) in the baseline and post-treatment MEG exams to assess treatment-related changes on a single-subject basis. Healthy control (HC) Veterans, matched for combat exposure, will be used to establish an MEG normative database. Test-retest reliability of MEG slow-wave source imaging for mTBI will also be examined.
Hypothesis 1: Veterans with mTBI will generate abnormal MEG slow-waves during the baseline MEG exam. Voxel-wise 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 test-retest reliability of MEG slow-wave source imaging is expected to be high, with intra-class correlation coefficient (ICC) 0.75 between two sequential MEG exams.
Hypothesis 2: In wakefulness, slow-wave generation is a signature of ongoing neural rearrangement/ healing, rather than a negative consequence of neuronal injury. IASIS treatment will enhance neural rearrangement/healing by initially potentiating slow-wave generation immediately after each treatment session.
Hypothesis 3: 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. In Veterans with mTBI who finish IASIS treatment, but not in the sham group, MEG source imaging will show a significant decrease in abnormal slow-waves at post-treatment exam. Such significant decreases will also be evident in both the voxel-wise and overall abnormal MEG slow-wave measures.
Specific Aim 2: To examine treatment-related changes in PCS and PTSD symptoms in Veterans with mTBI. PCS and PTSD symptoms will be assessed at the baseline and post-treatment follow-up visits.
Hypothesis 4: Compared with the sham group, mTBI Veterans in the IASIS treatment group will show significantly greater decreases in PCS symptoms between baseline and post-treatment assessments.
Hypothesis 5: Compared with the sham group, mTBI Veterans in the IASIS treatment group will also show significantly greater decreases in PTSD symptoms between baseline and post-treatment assessments.
Specific Aim 3: To study the relationship among IASIS treatment-related changes in rs-MEG slow-wave imaging, PCS, and neuropsychological measures in Veterans with mTBI. The investigators will correlate changes between baseline and post-IASIS abnormal rs-MEG slow-wave generation (i.e., total abnormal rs-MEG slow-wave and voxel-wise source imaging measures) with changes in PCS and neuropsychological tests performance.
Hypothesis 6: 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
- Model description
- After consent, Visit 1 (V1) for all 3 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 TES and sham groups will undergo a pre-session MEG, the first TES/Sham treatment Session (S1), and a post-session MEG. Next, the mTBI Veterans continue their TES/Sham treatments S2-6 in V4-8. During V9, a pair of pre- and post-MEG exams and NP will be performed. The mTBI Veterans will continue treatments S8-11 in V10-13. During V14, a pair of pre- and post-MEG exams will be performed. 1 week after the Veterans finish their final TES/Sham treatment S12, a 1-week follow-up MEG and NP will be conducted during V15. A subset of TES group will be tested 1 month after the final treatment for a follow-up MEG V16. Veterans in the mTBI-sham group will be offered the real TES treatment.
| Arm | Type | Receives |
|---|---|---|
| Transcranial Electrical Stimulation (TES) | Experimental | Device: TESmTBI Veterans blindly assigned to a 6 week of TES, either IASIS neurofeedback treatment or Nexalin, with 2-3 sessions per week. |
| Sham Treatment | Placebo comparator | Device: TESmTBI Veterans blindly assigned to a sham treatment for 6 weeks with 2-3 sessions per week. |
| Control | No intervention | –Veterans who are age-, gender-, education-, combat exposure-, and socioeconomically-matched. They will not undergo a treatment. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (19 listed)
- history of other neurological, developmental, or psychiatric disorders (based on the DSM-5 (MINI-7) [86] structured interview), e.g.,:
- 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.,:
- Potential subjects will be administered the Beck Depression Inventory (BDI-II) to evaluate level of depressive symptoms, and suicidal ideation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TESAlso: LIP-tES interventionThe EEG interface device is the J\&J Engineering I-330 C2. IASIS is delivered via the 4 EEG leads with respect to the Common Neck Reference. During each session, 2 electrodes are attached to the participant's left and right mastoids, while the remaining 2 electrodes are moved to various locations on the scalp to record EEG signals. All 4 electrodes are involved in applying weak electric current pulses back to the brain. The feedback signal consists 2 types of narrow pulse trains, both with 150mV in amplitude. The Nexalin device, FDA clearance (501K=K024377, Classification: Stimulator, Cranial Electrotherapy: CFR 882. 5800: U.S. Patent #6904322B2), produces a waveform that provides tES to the brain delivered at a frequency of 4Hz, 40Hz, and 77.5Hz at 0 to 15mA peak current. Evidence shows this waveform, at these frequencies, results in improved clinical outcomes for anxiety and pain. We hypothesize that repeated TES treatments serve to stimulate long-term neurochemical changes. | Device | Sham Treatment, Transcranial Electrical Stimulation (TES) |
Primary outcome
Change in Abnormal Magnetoencephalography (MEG) Slow-Waves (1-4 Hz) Activity
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 Magnetoencephalography (MEG) slow-waves (1-4 Hz) in mTBI Veterans. The unit of the abnormal MEG source activity was measured in pico Ampere-meter (or pA-m which is 10^(-12) A-m). Natural logarithm transformation (i.e., e-based) was used. So, the unit of the MEG source imaging was log(pA-m). The range of the voxel-wise MEG source activity scale is 0-10. High amplitude of the MEG source activity suggests more serious injury. In the present study, we measured the Difference score in MEG exam pre- vs post the transcranial electrical stimulation (TES) treatment. Our primary measure is the reduction of the abnormal MEG source activity for slow waves (1-4 Hz), defined as the MEG activity at the pre-TES exam minus that at the post-TES exam. So, the higher this difference score is, the better outcomes due to the TES treatment in reducing the abnormal MEG signal.
Rivermead Post Concussion Symptom Questionnaire
Time frame: Baseline through end of treatment, an average of 6 weeks
The Rivermead Post Concussion Symptom Questionnaire (RPQ) total score was used to assess change in post-concussion symptoms due to TES. Our focus in this analysis was the difference score in RPQ total score pre- vs post-treatment measures. The questionnaire has 16 items and uses scale of 0 - 4, with 0 as "not experienced at all" and 4 as "a severe problem." Value range: 0 - 64, where the higher scores mean a worse outcome. For this measure, we focused on the difference score: total score from prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
Neurobehavioral Symptoms Inventory
Time frame: Baseline through end of treatment, an average of 6 weeks
The Neurobehavioral Symptoms Inventory (NSI) total score was used to assess the changes of post-concussion symptoms due to TES. Our focus in this analysis was the difference score in NSI total score pre- vs post-treatment measures. The NSI has 22 items and uses a response scale of 0 - 4, with 0 as "none" and 4 as "very severe." Value range: 0 - 88, where the higher scores mean a worse outcome/more severe post-concussive symptoms. For this measure, we focused on the difference score: total score from prior to treatment minus total score from end of treatment. Therefore, the higher the difference score, the more positive change was observed.
9 secondary outcomes
The McGill Pain Questionnaire (MGPQ)
Time frame: Baseline through end of treatment, an average of 6 weeks
Clinician-Administered PTSD Scale (CAPS-5)
Time frame: Up to 6 weeks
Post-Concussion Check List (PCL-5)
Time frame: Up to 6 weeks
California Verbal Learning Test-2nd Edition - Free Recall Total Correct T-score
Time frame: Up to 6 weeks
Wechsler Adult Intelligence Scale-4th Edition (WAIS-IV) Processing Speed Index
Time frame: Up to 6 weeks
Delis-Kaplan Executive Function System (DKEFS) - Trail Number/Letter Switching Scaled
Time frame: Up to 6 weeks
Connors Continuous Performance Task II (CPT-II) - Inattention Omissions T-Score
Time frame: Up to 6 weeks
Barratt Impulsivity Scale
Time frame: Up to 6 weeks
Frontal Systems Behavior Scale
Time frame: Baseline through end of treatment, an average of 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25009772Huang MX, Nichols S, Baker DG, Robb A, Angeles A, Yurgil KA, Drake A, Levy M, Song T, McLay R, Theilmann RJ, Diwakar M, Risbrough VB, Ji Z, Huang CW, Chang DG, Harrington DL, Muzzatti L, Canive JM, Christopher Edgar J, Chen YH, Lee RR. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury. Neuroimage Clin. 2014 Jun 16;5:109-19. doi: 10.1016/j.nicl.2014.06.004. eCollection 2014.
- Background: PubMed 25769625Huang M, Risling M, Baker DG. The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury. Psychoneuroendocrinology. 2016 Jan;63:398-409. doi: 10.1016/j.psyneuen.2015.02.008. Epub 2015 Feb 23.
- Background: PubMed 25808909Robb Swan A, Nichols S, Drake A, Angeles A, Diwakar M, Song T, Lee RR, Huang MX. Magnetoencephalography Slow-Wave Detection in Patients with Mild Traumatic Brain Injury and Ongoing Symptoms Correlated with Long-Term Neuropsychological Outcome. J Neurotrauma. 2015 Oct 1;32(19):1510-21. doi: 10.1089/neu.2014.3654. Epub 2015 Jun 18.
- Background: PubMed 20808241MacGregor AJ, Dougherty AL, Galarneau MR. Injury-specific correlates of combat-related traumatic brain injury in Operation Iraqi Freedom. J Head Trauma Rehabil. 2011 Jul-Aug;26(4):312-8. doi: 10.1097/HTR.0b013e3181e94404.
- Background: PubMed 24367929MacDonald CL, Johnson AM, Nelson EC, Werner NJ, Fang R, Flaherty SF, Brody DL. Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel. J Neurotrauma. 2014 May 15;31(10):889-98. doi: 10.1089/neu.2013.3173. Epub 2014 Feb 10.
- Background: PubMed 19882478Hoffman SW, Harrison C. The interaction between psychological health and traumatic brain injury: a neuroscience perspective. Clin Neuropsychol. 2009 Nov;23(8):1400-15. doi: 10.1080/13854040903369433.
- Background: PubMed 22743844Vasterling JJ, Brailey K, Proctor SP, Kane R, Heeren T, Franz M. Neuropsychological outcomes of mild traumatic brain injury, post-traumatic stress disorder and depression in Iraq-deployed US Army soldiers. Br J Psychiatry. 2012 Sep;201(3):186-92. doi: 10.1192/bjp.bp.111.096461. Epub 2012 Jun 28.
- Background: PubMed 26444476Nelson DV, Esty ML. Neurotherapy of Traumatic Brain Injury/Post-Traumatic Stress Symptoms in Vietnam Veterans. Mil Med. 2015 Oct;180(10):e1111-4. doi: 10.7205/MILMED-D-14-00696.
- Background: PubMed 11346448Schoenberger NE, Shif SC, Esty ML, Ochs L, Matheis RJ. Flexyx Neurotherapy System in the treatment of traumatic brain injury: an initial evaluation. J Head Trauma Rehabil. 2001 Jun;16(3):260-74. doi: 10.1097/00001199-200106000-00005.
- Background: PubMed 22542638Huang MX, Nichols S, Robb A, Angeles A, Drake A, Holland M, Asmussen S, D'Andrea J, Chun W, Levy M, Cui L, Song T, Baker DG, Hammer P, McLay R, Theilmann RJ, Coimbra R, Diwakar M, Boyd C, Neff J, Liu TT, Webb-Murphy J, Farinpour R, Cheung C, Harrington DL, Heister D, Lee RR. An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes. Neuroimage. 2012 Jul 16;61(4):1067-82. doi: 10.1016/j.neuroimage.2012.04.029. Epub 2012 Apr 20.
- Background: PubMed 19385722Huang MX, Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J, Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D, Coimbra R, Lee RR. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.
- Background: PubMed 17510590Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S, Orrison WW. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55. doi: 10.1097/01.HTR.0000271115.29954.27.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mingxiong Huang, PhD principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TES in people with Mild Traumatic Brain Injury (mTBI) and Post-traumatic Stress Disorder, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Abnormal Magnetoencephalography (MEG) Slow-Waves (1-4 Hz) Activity (time frame: Baseline through end of treatment, an average of 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03244475, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2024.