Traumatic Brain Injury

The study is intended to cover two purposes: first, to develop a blood-based biomarker test for aiding the diagnosis of traumatic brain injury (TBI) in adult participants and for prognosis of outcome of TBI (CLIN12.1); and second, for monitoring the development of secondary events in adult participants diagnosed with TBI (CLIN12.2).

The CONNECT-TBI Trial aims to develop safe, effective treatments for complex mTBI that improve cognitive functioning. Based on the compelling preliminary data generated by our study team, the objective of this study is to conduct a randomized, double-blinded, sham-controlled Phase II clinical trial of APT-3 combined with rTMS, HD-tDCS, or sham to treat cognitive control deficits in Veterans with complex mTBI and PPCS. At the Baseline Visit, participants will undergo demographic, neuropsychological, behavioral, and quality of life testing. They will also undergo structural MRI to permit modeling of their brain, resting/task-related fMRI to identify the CCN, and pseudocontinuous arterial spin labeling (pCASL) and diffusion tensor imaging (DTI) to assess for other pathologies. They will then be randomized to 16 sessions of APT-3 with concurrent rTMS, HD-tDCS, or sham stimulation delivered to the unique functional left dorsolateral prefrontal cortex (DLPFC), a primary node of the CCN. Lastly, they will repeat all baseline tests, and report on 3- and 6-month recovery levels to establish longevity and stability of subjective benefit. Given that this individualization protocol has never been attempted for cognitive rehabilitation in military mTBI, we expect this trial will generate useful effect sizes for HD-tDCS and rTMS to be used for powering the next step, a Phase III multi-center trial.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality among children globally, with an estimated incidence ranging from 47 to 280 cases per 100,000 children (1). The burden of pediatric traumatic brain injury (pTBI) in low- and middle-income countries (LMICs) is characterized, because most pTBI occurs in LMICs (2). TBIs can have both short- and long-term effects including impairment of physical, cognitive, or emotional functions (3). Advances in acute trauma care have decreased mortality rates (4). Elevated intracranial pressure (ICP) following TBI or stroke has been recognized as an important second insult that is strongly correlated with increased mortality. Therefore, an increase in ICP can cause a decrease in brain perfusion and may result in brain ischemia (5). Early detection of raised intracranial pressure (RICP) is considered a better strategy to prevent secondary brain insult (6). The gold standard for ICP measurement is invasive techniques (i.e., ventriculostomy and intraparenchymal microtransducers), associated with risks, such as infection and haemorrhage (7). Several methods for noninvasive measuring of elevated ICP have been proposed: radiologic methods including computed tomography and ophthalmological techniques (8). Some brain computed tomography (CT) findings, such as brain parenchymal swelling, midline shifting, and compressed basal cisterns, are traditionally used for the indirect measurement of raised ICP (9). Among non-invasive methods, the measurement of optic nerve sheath diameter (ONSD) has gained particular interest (7). The optic nerve sheath is continuous with the meninges of the central nervous system and is encased with the subarachnoid membrane. Cerebrospinal fluid (CSF), located in the subarachnoid space, accumulates in the optic nerve sheath, thereby widening its diameter in the setting of increased ICP and limited intracranial compliance (10). Ultrasound assessments of ONSD could be a better option because of the low cost and rapid bedside operation without the need for radiation exposure, especially for cases that are unstable and require real-time monitoring of ICP in an intensive care unit (11). Despite existing research, there remains a gap in evaluating the diagnostic accuracy of the ONSD measured via ultrasound for the prediction of increased ICP in pediatric patients (12). This study aims to assess the diagnostic accuracy of bedside optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure in pediatric traumatic brain injury using brain CT findings as the reference standard.

The purpose of this research study is to evaluate the effectiveness of an exercise training intervention (24-36 sessions) to improve muscle strength and endurance in the lower limbs of individuals with paralysis. Specifically, surface electrical stimulation or previously implanted stimulator will be used to stimulate the muscles during various forms of exercise training with the primary focus on improving overall endurance and maximal power output. For this study, peripheral stimulating electrodes will send electrical signals to the muscles enabling the production of coordinated movements for exercise such as cycling or rowing.

Acute brain injury (ABI) is a leading cause of death and long-term disability in children. Diagnosis depends on fast neuroimaging, and head computed tomography (CT) is the bedside reference standard despite exposing the developing brain to ionizing radiation. A safe, portable, radiation-free bedside tool is needed to help decide which children need a head CT, to speed CT when injury is present, and to safely monitor injured children between scans. This study evaluates B-mode cranial point-of-care ultrasound (cPOCUS) performed through the temporal (and frontal) bone windows in children undergoing a clinically indicated head CT in the pediatric emergency department (ED) and pediatric intensive care unit (PICU). Children's thin skulls provide adequate acoustic windows in more than 95% of cases. cPOCUS is acquired by trained research scanners within 6 hours of head CT and interpreted offline by two blinded expert readers; the radiology CT report is the diagnostic gold standard. This is a prospective observational study; cPOCUS results are not returned to the clinical team in real time and do not change clinical care.

The purpose of this study is to evaluate a new virtual reality (VR)-based rehabilitation program designed to help individuals with traumatic brain injury (TBI) improve their walking abilities in real-world settings. By comparing immersive VR-assisted overground gait therapy to contemporary non-immersive, treadmill-based VR therapy (i.e., C-Mill), the investigators aim to determine its effectiveness in enhancing mobility and quality of life for TBI patients.

This study aims to develop and evaluate an AI-driven Personalized Exercise Feedback Program (AI-PEF) to enhance exercise adherence and health outcomes in mTBI patients. Methods: AI-PEF integrates the transtheoretical model and self-determination theory with machine learning algorithms to provide real-time, personalized feedback. A phased randomized controlled trial will be conducted: Phase I evaluates feasibility and acceptability through Delphi methods with expert consensus and patient feedback; Phase II validates preliminary outcomes with 30 participants in a 2-arm randomized trial; and Phase III assesses the program's impact on exercise adherence, exercise motivation, mHealth app usability, functional capacity, sleep quality, depressive symptoms, concussion symptoms, and quality of life with 90 participants in a 3-arm randomized trial. In Phase III, quantitative and qualitative data will be collected in parallel, with qualitative data collected through semi-structured interviews to explore participants' experiences and perceptions of the intervention.

This feasibility study investigates the potential of hypnosis as a complementary therapy for improving attentional deficits and reducing fatigue in patients with neurological conditions such as stroke, traumatic brain injury (TBI), and multiple sclerosis (MS). These patients often experience reduced spontaneous visual exploration and impaired functional independence despite current rehabilitation approaches. By integrating hypnosis with standard care and using EEG to monitor brain activity during hypnosis and sham-hypnosis sessions, this trial aims to evaluate the feasibility, acceptability, and preliminary efficacy of hypnosis in enhancing attention and reducing fatigue.

The purpose of this research is to understand and treat Traumatic Brain Injury (TBI) associated photophobia (light sensitivity) and its impact on visual function.

This study is evaluating whether pairing vagus nerve stimulation (VNS) with structured upper limb rehabilitation therapy can improve arm and hand function in individuals with chronic moderate to severe traumatic brain injury (TBI) and subsequent motor deficits. Many people who survive a TBI experience long-term weakness, poor coordination, and difficulty using one arm or hand. These motor impairments can significantly affect independence and quality of life. Traditional rehabilitation can help, but recovery is often incomplete. Vagus nerve stimulation (VNS) is an FDA-approved therapy for certain neurological conditions and involves a small device implanted under the skin in the chest with a lead connected to the vagus nerve in the neck. The device delivers mild electrical pulses to the nerve. In this study, VNS will be paired with goal-directed upper limb rehabilitation exercises. The stimulation is delivered during specific movements in therapy sessions. This "paired stimulation" approach is designed to enhance neuroplasticity - the brain's ability to reorganize and form new connections - which may improve motor recovery. The VNS device used in this study is FDA-approved for other conditions. However, its use paired with rehabilitation for upper limb recovery after traumatic brain injury is investigational. Participants in this study will: Undergo surgical implantation of the VNS device. Participate in structured upper limb rehabilitation therapy sessions where stimulation is paired with specific movements. Complete follow-up visits and assessments to measure changes in arm and hand function, strength, dexterity, and overall recovery. The main goal of the study is to determine whether paired VNS and rehabilitation improves upper limb motor function compared to rehabilitation alone. Safety will also be closely monitored, including surgical outcomes and any device-related effects. This study may help determine whether VNS paired with rehabilitation is a safe and effective way to enhance motor recovery after traumatic brain injury. Findings from this research could contribute to improved treatment strategies for individuals living with long-term motor impairments following TBI. If the results are promising, future studies plan to also include patients with acute TBI. Participation is voluntary. All participants will be carefully evaluated to determine eligibility, and informed consent will be obtained before enrollment.

This project will adapt a currently deployed Clinical Decision Support (CDS) system to deliver a VTE prevention guideline for adult patients with traumatic brain injury (TBI). We believe this is an ideal PCOR use case given PCORI's continued effort to combat VTE in trauma and our experience previously implementing this guideline. The Our overall goal is to successfully scale, evaluate, and maintain an interoperable TBI CDS across 7 total institutions.

The goal of this clinical trial is to evaluate the effectiveness of a home-based cognitive-motor telerehabilitation program in individuals with traumatic brain injury (TBI) following discharge from intensive inpatient neurorehabilitation. The main questions it aims to answer are: * Does home-based cognitive-motor telerehabilitation improve functional independence, cognitive performance, mobility, and quality of life in individuals with TBI? * Are the effects of home-based cognitive-motor telerehabilitation superior to those achieved with standard outpatient rehabilitation? The study will compare a home-based cognitive-motor telerehabilitation program with standard outpatient rehabilitation to determine their relative effects on functional recovery. Participants will: * Receive either home-based cognitive-motor telerehabilitation or standard outpatient rehabilitation, according to the assigned treatment pathway. Both rehabilitation programs consist of 20 sessions lasting 45 minutes each, three times per week. * Undergo clinical, cognitive, and motor assessments at predefined study time points: T0 (hospital discharge, pre-intervention), T1 (post-intervention, 7 weeks after T0), and T2 (follow-up, 6 months after T0). * Be evaluated for changes in functional independence, cognitive functioning, mobility, quality of life, and caregiver burden.

The goal of this clinical trial is to test the safety of the drug Angiotensin (1-7) and learn whether it works well as a treatment in people who have suffered a moderate to severe traumatic brain injury (TBI). The main questions this trial aims to answer are: * Is Angiotensin (1-7) safe? * Does Angiotensin (1-7) improve mental functioning and reduce physical signs of brain damage in people who have suffered a moderate to severe TBI? Participants will: * Complete 21 days of study treatment consisting of a once-daily injection. * Provide blood samples. * Undergo two magnetic resonance imaging (MRI) scans of the brain. * Complete specific tasks and questionnaires that allow researchers to evaluate the participant's brain and psychological functioning. Researchers will compare three groups: two groups that receive different doses of Angiotensin (1-7) and one group that receives a look-alike treatment with no active drug. This will allow researchers to see if the drug has any negative effects and whether it improves mental functioning and physical signs of brain damage after a TBI.

A study examining the effects of creatine supplementation to improve recovery after brain injury in children and teenagers.

The goal of this clinical trial is to learn whether the ZEPU-2000A, ZEPU-2000D and ZEPU-2000E robotic rehabilitation trainers help people with weakness or movement problems in their arms and legs. These devices are used to guide repeated arm and leg movements as part of rehabilitation therapy. The study will also look at whether the devices are safe to use. The main questions it aims to answer are: Is training with the ZEPU-2000 devices safe, and how well do patients tolerate and stick with the training sessions? Does adding robotic training to usual rehabilitation improve muscle strength, joint movement, balance, walking, and daily function more than usual rehabilitation alone? Researchers will compare a group receiving robotic-assisted rehabilitation plus usual care to a group receiving usual rehabilitation care alone, to see whether the robotic devices provide added benefit. Participants will: Be adults aged 18-60 with arm and/or leg movement problems caused by stroke, incomplete spinal cord injury, traumatic brain injury, or an orthopedic condition Attend training sessions 3 times a week for 12 weeks (about 36 sessions total), each lasting approximately 45 minutes Undergo assessments of strength, movement, balance, and daily function at the start of the study and every 2 weeks throughout the 12-week period Be monitored for any side effects or safety concerns, such as skin irritation, falls, or discomfort, at every session

Traumatic Brain Injury (TBI) often results in a wide array of cognitive impairments, which can significantly diminish quality of life for affected individuals. While traditional rehabilitation methods typically adopt a standardized approach, it's crucial to acknowledge the significant heterogeneity within the TBI patient population. Neglecting these variations reduces the likelihood of otherwise effective treatments being considered for widespread adoption. Emerging evidence highlights the potential of transcranial direct current stimulation (tDCS) as a promising adjunctive therapy. tDCS, a noninvasive and safe neuro-rehabilitative procedure, has shown efficacy when integrated with cognitive training across various neurological disorders, such as depression, post-stroke aphasia, and neurodegenerative conditions. This study aims to investigate the effectiveness of tDCS paired with behavioral therapy, particularly cognitive training, in improving cognition and executive function in chronic TBI patients. Additionally, tDCs targets in the current study will be tailored to each individual patient, recognizing the patient's unique needs and circumstances

This study tests whether two non-invasive tools can help paramedics detect dangerously high pressure inside the skull in patients with a sudden brain injury, such as stroke or head trauma, before they reach the hospital. The tools are a wearable sensor called Brain4care, placed on the head, and an ultrasound measurement of the eye's optic nerve. Neither tool requires needles, incisions, or any invasive procedure. The study has two parts. In the first part, researchers will use both tools on patients treated by the Mobile Emergency Care Service (SAMU) in Salvador, Brazil, to check how accurately the tools can detect high pressure inside the skull. The results from these tools will not be used to guide the patient's care during this part of the study. In the second part, some patients will be assessed using these tools as part of their emergency care, while other patients will receive standard emergency care. Researchers will compare how often each group of patients is correctly sent to a hospital with the specialized brain surgery services they may need. The goal of this research is to help emergency teams identify patients with dangerous brain pressure earlier and get them to the right hospital faster, which may improve their chances of recovery.

The goal of this pilot randomized controlled trial is to learn whether the ZEPU-SG1PLUS Hand Functional Comprehensive Training System - a robotic device used alongside standard rehabilitation - is safe, feasible, and helpful for people with upper limb (arm/hand) motor problems caused by stroke, incomplete spinal cord injury, traumatic brain injury, or orthopedic conditions. The main questions it aims to answer are: Is robotic-assisted hand training well tolerated by patients, and can it be safely added to standard rehabilitation, with acceptable rates of device-related side effects? Does adding robotic hand training to standard rehabilitation improve arm and hand strength, range of motion, and functional ability compared with standard rehabilitation alone? Is it practical to fit this type of robotic training into everyday rehabilitation services at Bangladesh Medical University? Researchers will compare a robotic-augmented rehabilitation group to a standard-care (control) group to see whether adding robotic hand training works better than usual rehabilitation alone. Participants will: Be randomly assigned to one of two groups: one receiving standard rehabilitation plus robotic hand training with the ZEPU-SG1PLUS device, and one receiving standard rehabilitation alone If assigned to the robotic training group, attend three training sessions per week for 12 weeks, each lasting about 30-45 minutes, at the Robotic Rehabilitation Centre, BMU Undergo assessments at the start of the study and at two-week intervals during the 12-week program and follow-up period, including tests of muscle strength, joint movement, hand function, and daily activity ability Be monitored throughout for any side effects or safety concerns related to the training

This study uses a non-invasive (external) ultrasound test called Transcranial Doppler (TCD) to measure how blood flows through the major arteries of the brain of children receiving care in the Pediatric Intensive Care Unit (PICU). TCD is already used for clinical reasons in many children, but it is not part of routine monitoring for every critically ill child. By using TCD, the investigators hope to better understand how brain blood flow changes during illness. They will also track children's functional status from before their illness to the time of PICU discharge to explore how brain blood flow patterns relate to neurological outcomes.125 participants will be enrolled and will be on study while in the PICU, estimated to be 3-14 days.

Traumatic brain injury (TBI) can have long-term and chronic effects on an individual's physical, social, and emotional health, impacting quality of life and the ability to engage in meaningful life roles. Despite the potential for long-term effects, much of the care for individuals with TBI is front-loaded in the weeks to months post-injury. Self-management and self-management training are key components of long-term care for many chronic health conditions, but they are not standard parts of care for individuals with TBI. In this study the investigators will address two objectives: 1) identify self-management priorities from the perspectives of individuals with chronic TBI, families, and health care providers and 2) pilot test an existing virtual community-based self-management training program (the Chronic Disease Self-Management Program (CDMSP)), to a) evaluate changes in quality of life, self-management self-efficacy, and other patient-reported outcomes before and after participating in the training, and b) identify barriers and facilitators to participating in community-based self-management training.

This study is designed to better understand the long-term effects of hyperbaric oxygen therapy (HBOT). Our goal is to determine whether improvements after treatment are maintained over time and whether additional benefits appear months after treatment has ended. We will evaluate changes in cognitive function, mental health, and daily functioning to help strengthen the scientific evidence supporting the use of HBOT and guide future treatment recommendations.

The goal of this prospective observational study is to determine whether the trajectory of optic nerve sheath diameter (ONSD) after osmotherapy weaning can predict rebound intracranial hypertension in adult patients with traumatic brain injury requiring osmotherapy for elevated intracranial pressure. The main questions it aims to answer are: Does the trajectory of ONSD during osmotherapy weaning predict the development of rebound intracranial hypertension? What is the diagnostic accuracy of serial ONSD measurements for the early detection of rebound intracranial hypertension? Researchers will compare patients who develop rebound intracranial hypertension with those who do not to determine whether changes in ONSD trajectory differ significantly between the two groups. Participants will: Undergo serial bedside ocular ultrasound examinations for ONSD measurement at predefined time points after osmotherapy weaning. Receive standard clinical management for traumatic brain injury according to institutional protocols; no additional therapeutic intervention will be administered. Undergo routine neurological assessments, laboratory investigations, and neuroimaging as clinically indicated. Be followed for the occurrence of rebound intracranial hypertension and relevant clinical outcomes during their ICU stay

Some patients with severe traumatic brain injury cannot respond at the bedside, yet about 1 in 4 may be aware but unable to show it - a hidden state called cognitive motor dissociation. This study tests a gentle, non-invasive treatment delivered through clips on the left ear that stimulates two nerves at once: the vagus nerve at the inner ear (taVNS) and the trigeminal nerve at the outer ear (taTNS). Each nerve has separately been shown to help people with disorders of consciousness recover, but they have not been combined before. All enrolled patients receive the stimulation for one hour a day, with continuous heart and oxygen monitoring and a pain-protection check used to keep the dose safe. The study measures recovery two ways: the Coma Recovery Scale-Revised (CRS-R), scored by clinicians, and SeeMe, an automated camera system that detects tiny command-driven movements the eye cannot see.

MINT is a single-site, prospective, randomized, double-blind, sham-controlled pilot trial evaluating the safety and feasibility of transcutaneous auricular vagus nerve stimulation (taVNS) in patients with moderate to severe traumatic brain injury (GCS 3-12). Participants will be randomized to receive either active taVNS or sham stimulation using the same device. The primary objective is to assess the safety and feasibility of taVNS implementation in the acute TBI setting. Secondary objectives include exploratory measurement of serum inflammatory and neuronal injury biomarkers and assessment of functional outcome using the Extended Glasgow Outcome Scale at hospital discharge.

This project will develop a wearable rehabilitation robot suitable for in-bed acute stage rehabilitation. It involves robot-guided motor relearning, passive and active motor-sensory rehabilitation early in the acute stage post-TBI including patients who are paralyzed with no motor output. The early acute TBI rehabilitation device will be evaluated in this clinical trial.