Clinical Research Directory

Improving In-hospital and Post-discharge Patient Education for Mild Traumatic Brain Injury

The purpose of this study is to develop and validate ways to provide better patient education and clinical management for individuals who go to the emergency department (ED) with concussion or mild traumatic brain injury (mTBI).

CoMind Early Feasibility Study

The purpose of this research, which has been determined as non-significant risk by the central IRB overseeing the study, is to obtain information to help further develop a machine (a medical device) to measure the pressure around the brain from the outside (this pressure is called intracranial pressure or ICP). Monitoring and managing ICP is an important part of care for patients with conditions such as Traumatic Brain Injury (TBI). However, the current way of measuring ICP requires surgery to drill a hole into the skull, and therefore can introduce additional risks such as infections and pain. Recent research has shown it may be possible to measure ICP without needing surgery. This technology is in development, but large amounts of data is required to build these new devices. Through collecting a large database of information from patients who have both the routine surgical device and the research device applied to their head, the research team will work to develop and test an effective and potentially safer way of monitoring patient ICP.

Assessment of Traumatic Brain Injury Using Transcranial Magnetic Stimulated Evoked Potentials

Patients evaluated at Penn Presbyterian Medical Center for traumatic brain injury (TBI), who sign the informed consent, will undergo assessment of electrophysiologic potentials evoked by transcranial magnetic stimulation (TMS), using the Delphi-MD device (QuantalX Neuroscience Ltd., Saba Israel).

Evaluation and Diagnosis of Potential Research Subjects With Traumatic Brain Injury

Background: \- The Center for Neuroscience and Regenerative Medicine is working to improve physicians' understanding of brain injury. More information is needed on traumatic brain injury (TBI), especially how well a person recovers from TBI and how the brain changes over time in people with TBI. To conduct this research, the center is sponsoring a number of research studies on TBI and is interested in evaluating individuals with TBI or post-concussive syndrome to determine if they might be eligible for future studies. Objectives: \- To develop a pool of individuals with traumatic brain injury and post-concussive syndrome for future research studies. Eligibility: \- Individuals at least 18 years of age who have symptoms of or have been diagnosed with traumatic brain injury or post-concussive syndrome and are willing to participate in future studies. Design: * Participants will be screened with an initial telephone interview, and will be asked to come to the National Institutes of Health for an in-person screening visit. * At the screening visit, participants will provide a medical history, have a physical examination and complete a study questionnaire on their TBI and its symptoms, including how the injury occurred, when it occurred, and any previous brain-related injuries. * Subjects may also return for a second visit at the NIH CC if eligible. * Each visit may involve blood samples, an MRI scan, and a series of tests to evaluate brain function. * Participants will also provide contact information to enable researchers to contact them for future studies.

Predict Severe Traumatic Brain Injury

Severe traumatic brain injury (TBI) is associated with a 20-30% mortality rate and significant disability among most survivors. The Centers for Disease Control and Prevention (CDC) estimate that 2% of the U.S. population lives with disabilities directly attributable to TBI, with annual costs exceeding $76.5 billion. Current treatments are largely ineffective because they are instituted after irreversible damage has already occurred. By the time intracranial pressure (ICP) increases or brain tissue oxygen tension (PbtO2) decreases to harmful levels, it is often too late to reverse or repair the damage. A computerized method has been developed that can predict these injurious events ahead of time, allowing clinicians to intervene before further damage occurs. The goal of this proposal is to test these predictions in real time. The first phase of the project (Year 1) involves setting up the informatics infrastructure, with no patient interaction. In the second phase (Year 2), subjects, through surrogate decision-makers, will be enrolled in an observational study where data on intracranial pressure and brain tissue oxygen tension will be collected, and the prediction algorithm will be tested for accuracy. Clinical management will follow standard care protocols, and no additional interventions will be performed. Approximately 120 individuals will participate in this study at the University of Chicago and Ben Taub General Hospital in Houston. Data collected will include both the electronic medical record and data from bedside intensive care unit monitors. The electronic medical record includes demographic information, injury characteristics, laboratory values, and imaging data, while the intensive care unit monitor provides real-time vital signs such as intracranial pressure, brain tissue oxygen tension, and mean arterial pressure. These data will be securely stored in a research computer database. Efforts will be made to contact subjects or their caretakers at 6 months to follow up on recovery. This research aims to improve patient outcomes by providing predictions of further brain injury, with the potential for future interventions to prevent permanent brain damage.

Clinical Evaluation of the i-STAT TBI Test

The goal of this study is to evaluate the i-STAT TBI test to assist determining the need for a computed tomography (CT) scan in patients with suspected mild traumatic brain injury (TBI). Patients will be asked to provide a blood sample.

Cortical Spreading Depolarization After Severe Traumatic Brain Injury

Preliminary evaluation of electrodes placed on the brain for recording brain activity and novel algorithms to determine cortical spreading depolarization foci of origination following severe traumatic brain injury requiring neurosurgical intervention.

SmART-TBI: Supplementation With Amino Acid Rehabilitative Therapy in TBI

The most persistent and disabling postconcussive symptoms following mild traumatic brain injury (mTBI) are sleep disturbances and cognitive dysfunction, with few tractable interventions currently available. Here, a novel therapy will be tested consisting of dietary supplementation with branched chain amino acids (BCAA), based on the study team's previous preclinical work showing restoration of glutamate neurotransmitter balance in sleep and memory circuits. Supplementation with Amino acid Rehabilitative Therapy in TBI (SmART-TBI) is a randomized, placebo-controlled, double-blinded, exploratory clinical trial of BCAA intended to establish the feasibility, acceptability, and limited efficacy of long-term BCAA to improve sleep and cognition in Veterans with mTBI. These results will inform the optimal study design of a future, full-scale randomized controlled trial, including the identification of the proper dose and duration of BCAA to improve sleep and the potential subpopulations of Veterans with mTBI that may benefit the most.

Fareon Open Label Device Clinical Trial

The purpose of this study is to assess the safety and feasibility of an at-home MMT treatment in patients with cognitive dysfunction related to acquired brain injury, Long COVID, traumatic brain injury, myalgic encephalomyelitis (ME/CFS), and other neurodegenerative diagnoses including but not limited to Alzheimer's disease and to collect data on safety and efficacy to inform the design of larger clinical studies.

Blood NfL and Functional Outcomes After Moderate-to-Severe TBI

Prospective cohort study of 150 adults with moderate-to-severe TBI. Blood NfL is measured at admission, day 1, and day 3 to examine its relationship, alone and with CT imaging, to 3-month functional outcome (GOSE).

Andexanet Alfa for Reversal of Factor Xa Inhibitors in Traumatic Brain Injury: A Retrospective Single-Centre Study

Elderly patients on direct oral anticoagulants (DOACs), specifically factor Xa (FXa) inhibitors such as apixaban and rivaroxaban are at elevated risk of haematoma expansion following traumatic brain injury (TBI). Andexanet alfa is a recombinant modified factor Xa decoy protein that directly reverses the anticoagulant effect of FXa inhibitors. The pivotal ANNEXA-4 single-arm trial reported hemostatic efficacy of approximately 82% in the overall cohort and 82.9% among patients with intracranial haemorrhage (ICH). The subsequent ANNEXA-I randomised controlled trial demonstrated 67.0% hemostatic efficacy with andexanet alfa compared with 53.1% in the usual-care group (adjusted difference 13.4 percentage points; p=0.003) among patients with spontaneous ICH. However, both landmark trials were focused predominantly on spontaneous ICH, and TBI-specific real-world data on andexanet alfa remain limited. This retrospective single-centre cohort study evaluates the hemostatic efficacy and safety of andexanet alfa in adult patients with traumatic intracranial haemorrhage who were received FXa inhibitor anticoagulation. All patients had a baseline computed tomography (CT) scan and at least one follow-up CT within 24 hours of andexanet alfa administration. The primary outcome is the proportion of patients achieving excellent or good hemostatic efficacy, defined by the percentage change in haematoma volume (for intraparenchymal haemorrhage, IPH) or maximum thickness (for subdural haematoma, SDH; epidural haematoma, EDH; or subarachnoid haemorrhage, SAH) between baseline and follow-up CT: Excellent (≤20% increase), Good (21-35% increase), or Poor (\>35% increase). Key secondary outcomes include 30-day all-cause mortality, thrombotic complications (deep vein thrombosis, pulmonary embolism, ischaemic stroke, myocardial infarction), reduction in anti-factor Xa activity, neurosurgical intervention rate, and hospital and ICU length of stay.

Cognitive Effects of Hyperbaric Oxygen Therapy (HBOT) After a Traumatic Brain Injury

This is a retrospective, single-center observational study evaluating the cognitive effects of hyperbaric oxygen therapy (HBOT) in adults who sustained a traumatic brain injury (TBI). Earlier randomized controlled work at this center demonstrated cognitive improvement after HBOT in patients with chronic deficits following mild TBI. This study evaluates a large sample size and operationalizes HBOT treatment as a continuous variable in the form of a cumulative oxygen dose, something has not been done before. Using the medical records of patients treated at the Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center between 2008 and 2026, the investigators compare computerized NeuroTrax cognitive assessments obtained before and after HBOT. The investigators quantify within-patient change across the cognitive domains and the Global Cognitive Score, and test whether the magnitude of cognitive change is associated with cumulative oxygen dose, expressed as the area under the pressure-time curve (ATA-minutes). The study includes patients across all TBI severity grades and adjusts for baseline performance, age, sex, and injury severity.

TRACK-TBI Precision Medicine Part 3 - Option II

The purpose of this study is to determine if experimental drug treatment improves recovery after TBI as compared to a control (placebo) group. Changes in recovery will be measured throughout the study. The study drug listed below is approved by the U.S. Food and Drug Administration (FDA) but is being used "off-label" in this study. This means that the drug is not currently approved to treat TBI.

Targeted Noninvasive Brain Stimulation (T-NIBS) to Improve Hand Motor Functions in Acquired Brain Injury

Acquired Brain Injury (TBI) is a serious medical and health problem in the US. Individuals with an acquired brain injury due to stroke and Traumatic Brain Injury (TBI) commonly suffer from upper extremity physical impairments that persist even after years of injury; these deficits are attributed to the damage to brain structure and changes in structural and functional connectivity. Although the conventional rehabilitation approaches are helpful in assisting motor recovery often there is a complaint of fatigue due to the repetitive tasks and also, nearly half of the ABI survivors do not regain their ability to use their arms for daily activities. To address this issue, Dr. Shenoy's proposed study will investigate the combined use of individually targeted non-invasive brain stimulation and music-assisted video game-based hand exercises to achieve functional recovery. Further, the project will also investigate how the intervention modulates brain activity (recorded using EEG) in terms of brain connectivity before- and after the -intervention. In the end, this study will allow us to understand the cortical dynamics of ABI rehabilitation upon brain stimulation. Extending further, this could pave the way to advance the knowledge of behavioral and neural aspects of motor control in patients with different types of neuromuscular disorders.

High Intensity Step Training After Traumatic Brain Injury

This study will explore whether the types and intensity of the interventions being delivered will yield measurable cognitive benefits in addition to improved mobility and balance. The study evaluates three therapeutic approaches to improve mobility and balance after traumatic brain injury (TBI): Conventional Gait and Balance Training, high intensity step training, and high intensity step training with virtual reality.

Closed Versus Open Endotracheal Suctioning and Ventilator-Associated Pneumonia in Severe Traumatic Brain Injury

This randomized controlled trial will compare closed versus open endotracheal suctioning techniques for preventing ventilator-associated pneumonia (VAP) in adults with severe traumatic brain injury (TBI) who need mechanical ventilation for more than 48 hours. Patients will be randomly assigned to suctioning with a closed in-line system or with a sterile open technique that disconnects the ventilator. The main outcome is the incidence density of VAP per 1,000 ventilator-days. Other outcomes include oxygenation after suctioning, duration of mechanical ventilation, intensive care unit (ICU) length of stay, and ICU mortality.

Psychoactive Drug Use and Acute Care Use After Trauma and Out-of-Hospital Cardiac Arrest

This retrospective population-based cohort study uses linked administrative healthcare data from the Local Health Authority of Bologna (Italy) to describe the use of four classes of psychoactive drugs (opioids, antiepileptics, antipsychotics, and antidepressants) after hospital discharge in two populations, adults admitted urgently for trauma and adults surviving out-of-hospital cardiac arrest, and to evaluate whether post-discharge exposure is associated with low-acuity or incomplete emergency department visits and urgent hospital readmissions within one year. Exposure is derived from outpatient dispensing records and classified as naive (started after discharge), long-term (before and after), or interrupted, and as current or not current over follow-up. Associations are estimated with marginal count regression models adjusted for demographics, illness or injury severity, and comorbidity, separately for each cohort.

hCG Treatment for Rehabilitation From a TBI

The COGNI-REHAB Trial is a single-site, phase O/I, randomized, double-blind, placebo-controlled study of human chorionic gonadotropin (hCG; choriogonadotropin alfa, Ovidrel®) in men with post-acute, moderate to severe traumatic brain injury (msTBI). Its objective is to assess the safety and efficacy of a 24-week regimen of Ovidrel (125 micrograms twice weekly) compared to placebo on treatment-emergent adverse events (TEAEs), cognitive and functional recovery, and circulating sex hormones.

A Study to Develop a Blood-based Test for Aiding the Diagnosis/Prognosis of Traumatic Brain Injury in Adults and for Monitoring the Development of Secondary Events in Patients Diagnosed With 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).

Transcutaneous Auricular Vagus Nerve Stimulation to Improve Upper Extremity Recovery After Traumatic Brain Injury

Upper extremity weakness, impaired coordination, reduced dexterity, and limited arm and hand use may continue after TBI. Repetitive, task-specific rehabilitation may improve function, but recovery can remain incomplete. taVNS is a non-invasive form of electrical stimulation delivered to part of the outer ear. The stimulation is intended to activate nerve pathways involved in learning and brain plasticity while you practice upper extremity tasks. This pilot study will evaluate safety, tolerability, feasibility, and preliminary effects on upper extremity function and cognition. Up to 40 people will take part at Craig Hospital.

Effects of Rapid-Resisted Exercise and Bright Light Therapy on Ambulatory Adults With Traumatic Brain Injury

Background: * Traumatic brain injury may have a range of effects, from severe and permanent disability to more subtle functional and cognitive deficits that often go undetected during initial treatment. To improve treatments and therapies and to provide a uniform quality of care, more research is needed into different treatments for traumatic brain injury. * Exercise has been shown to improve movement and balance in people with strokes, cerebral palsy, and other conditions that affect the brain, and can improve symptoms of memory problems or depression. Bright light therapy has also been shown to improve mood in people with depression. Researchers are interested in studying problems with movement, balance, thinking, and mood in people with traumatic brain injury. By comparing the effects of exercise and bright light exposure on brain function, new treatments may be developed for acute traumatic brain injury. Objectives: \- To compare the effects of exercise and bright light therapy on the brain function of individuals with traumatic brain injury. Eligibility: \- Individuals between 18 and 44 years of age who either have been diagnosed with traumatic brain injury or are healthy volunteers. Design: * Individuals with traumatic brain injury will have four outpatient evaluation visits at the clinical center, a 3-month home exercise program, and a 3-month bright light exposure program at home. Healthy volunteers will have one evaluation visit at the clinical center. * At the first study visit, all participants will have a full physical examination and medical history. Individuals with traumatic brain injury will also have an eye exam to determine if it is safe for them to receive light therapy. * All participants will have the following initial tests: * Tests of walking and movement, including monitoring by a physical therapist; tests to record joint movement and evaluate muscle function; tests that combine movement, thinking, and speaking; and balance and reaction time tests. * Magnetic resonance imaging scans * Tests of thinking and mood, including questionnaires, computerized tests, and simple action tests. * Participants with traumatic brain injury will have separate 3-month sessions of exercise and bright light therapy, with additional evaluation visits between each 3-month session and at the end of the study. Between the 3-month sessions, participants will have 1 month with no intervention. * Exercise sessions will involve regular workouts on an elliptical machine for 30 minutes for 5 days a week, and bright light therapy sessions will involve sitting in front of a light box for 30 minutes for 5 days a week. Participants will keep a journal to monitor the effects of the therapy.

Group Lifestyle Balance™ for Individuals With Traumatic Brain Injury (GLB-TBI)

The purpose of this RCT is to examine the efficacy of a Group Lifestyle Balance™ (GLB) program adapted for people with traumatic brain injury (TBI) on primary (weight) and secondary outcomes at 3, 6, 12, and 18 months from enrollment into the program.

Safety of Cultured Allogeneic Adult Umbilical Cord or Placental Derived Mesenchymal Stem Cell Intravenous Infusion for TBI

This trial will study the safety and efficacy of intravenous infusion of cultured allogeneic adult umbilical cord or placental derived mesenchymal stem cells for the treatment of traumatic brain injury

The Impact of Community-based Wellness Programs on The Triple Aim

People with disabilities experience a staggering incidence of secondary conditions that can result in death or negatively impact their health, participation in the community, and quality of life. Many of these chronic secondary conditions are preventable. The Institute for Healthcare Improvement has advocated for optimizing care through programs that simultaneously improve health and the patient experience of care, while reducing cost, called the "Triple Aim." Studies have shown that the Triple Aim can be achieved through programs that facilitate community integration; however the U.S. healthcare system lacks a paradigm of care for individuals with disabilities that promotes community integration. In order to identify potential models of healthcare delivery for individuals with disabilities that are effective in achieving the Triple Aim, we will conduct a rigorous research project to evaluate the impact of two different models of care on the Triple Aim: 1) a community-based care management program delivered by a non-profit organization through waiver funds, and 2) the Program for All-inclusive Care for the Elderly (PACE) applied to younger individuals with disabilities between ages 55-64.