N/A N=66 Randomized Double-blind Treatment

Transcranial Electrical Stimulation for mTBI

Mild Traumatic Brain Injury (mTBI) · Post-traumatic Stress Disorder

Bottom Line

View on ClinicalTrials.gov: NCT03244475 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jan 2024

Primary outcome: Primary: Change in Abnormal Magnetoencephalography (MEG) Slow-Waves (1-4 Hz) Activity — 1.8; 0.2; 0 units on a scale — p=0.01

Study Design & Population

Study type: Interventional
Phase: N/A
Interventions: TES (Device)
Age: Adult · 18+ yrs
Sex: All
Sponsor: VA Office of Research and Development
Primary completion: Sep 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Abnormal Magnetoencephalography (MEG) Slow-Waves (1-4 Hz) Activity	1.8; 0.2; 0	0.01 sig
PRIMARY Rivermead Post Concussion Symptom Questionnaire	11.1; 10.9; 0	0.05
PRIMARY Neurobehavioral Symptoms Inventory	12.3; 12.7; 0	0.05
SECONDARY The McGill Pain Questionnaire (MGPQ)	14.8; -5.1; 0	0.05
SECONDARY Clinician-Administered PTSD Scale (CAPS-5)	6.5; 4.2; 0	0.05
SECONDARY Post-Concussion Check List (PCL-5)	14.9; 12.1; 0	0.05
SECONDARY California Verbal Learning Test-2nd Edition - Free Recall Total Correct T-score	-6.7; -2.8; 0	0.05
SECONDARY Wechsler Adult Intelligence Scale-4th Edition (WAIS-IV) Processing Speed Index	-5.06; -11.48; 0	0.05
SECONDARY Delis-Kaplan Executive Function System (DKEFS) - Trail Number/Letter Switching Scaled	-0.77; -2.08; 0	0.05
SECONDARY Connors Continuous Performance Task II (CPT-II) - Inattention Omissions T-Score	5.71; -0.89; 0	0.05
SECONDARY Barratt Impulsivity Scale	7.6; 2.4; 0	0.05
SECONDARY Frontal Systems Behavior Scale	9.1; 3.2; 0	0.05

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). 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.

Eligibility 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03244475). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.