Clinical Research Directory

Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)

The purpose of this study is to determine whether growth hormone replacement therapy (GHRT) is effective versus placebo in the improvement of Quality of Life in patients with adult growth hormone deficiency (AGHD) and mild traumatic brain injury (mTBI).

rTMS Target Identification for Functional Disability in AUD+mTBI

The objectives of this VA Merit application are to identify a neural target unique to Veterans with co-occurring alcohol use disorder and mild traumatic brain injury (AUD+mTBI) and to test the efficacy of this target as a stimulation site for repetitive transcranial magnetic stimulation (rTMS) treatment to maximize functional recovery. rTMS will soon be a treatment option at 30 VAs nationwide and preliminary studies show promise for AUD and mTBI treatment. A better understanding of how AUD+mTBI impacts the brain needs to occur in order to advance rTMS to optimize function. This research is aligned with the VA RR\&D's mission to generate knowledge and innovations to advance the rehabilitative health and care of Veterans, to effectively integrate clinical and applied rehabilitation research, and translate research results into practice. This research is also aligned with the goal of the Psychological Health \& Social Reintegration portfolio to develop interventions improving psychological health status of Veterans enabling them to function more fully in society.

Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion

Concussions are very common. Although many people recover well from concussion, some will have persistent symptoms and difficulties with daily activities. How people cope with their symptoms following concussion powerfully influences their recovery. Fear avoidance behaviour is a particularly unhelpful approach to coping, in which people perceive their pre-injury activities as unnecessarily dangerous and take great care to avoid overexertion and overstimulation. The investigators developed and pilot tested a behavioural therapy, called graded exposure therapy, to reduce fear avoidance behaviour. Our preliminary work suggested that graded exposure therapy was acceptable to patients with concussion and possibly beneficial for their recovery. The GET FAB after concussion study will assess the effectiveness of graded exposure therapy.

TES HT100 Clinical Validation for Brain Injury Screening in Patients With Mild Head Trauma or Neurological Symptoms

The goal of this clinical study is to evaluate how accurately and safely the TES HT100 device can identify intracranial abnormalities in adult emergency department patients with mild head trauma or neurological symptoms that are not related to trauma and are not immediately life-threatening. The main questions it aims to answer are: * How well does TES HT100 identify patients with intracranial abnormalities compared with head CT, the reference standard? * Is TES HT100 safe to use in this patient population? * Could TES HT100 help improve patient triage and use of hospital resources in the emergency setting? Researchers will compare the result of TES HT100 with the head CT report. Participants will: * Be enrolled if they are adults presenting to the emergency department with mild head trauma or selected neurological symptoms * Undergo standard clinical assessment and head CT according to usual care * Have an additional TES HT100 examination lasting about 5 minutes, performed by trained personnel * Be assessed for device performance and any adverse events related to use of the device

Evaluating Huddles as a Novel Approach to Improving Concussion Safety

Investigators will conduct a randomized controlled trial assessing the effectiveness and implementations of Pre-Game Safety Huddles (Huddles) in youth soccer.

Targeting Neuroplasticity for Persistent Post-Concussive Cognitive Symptoms

This project investigates an innovative combination of non-invasive neuromodulation (transcranial direct current stimulation - tDCS) and cognitive training as a novel treatment approach aimed at improving function in individuals suffering from persistent post-concussive syndrome (PPCS) following mild traumatic brain injury (mTBI).

Transcranial Ultrasonography for the Management of Patients With Mild TBI

The investigators hypothesize that patients with mild TBI and normal TCD can be safely discharged home immediately after the ED. The targeted population is the category of patients eligible for early discharge: 1) patients with mild lesions on the initial CT scan and a GCS 15 after CT scan completion and, 2) patients with no lesion on the initial cerebral CT scan with at least one of the following risk factors: GCS 14 after CT scan completion, persisting post-traumatic nausea/vomiting/headaches, concomitant alcoholic intoxication or patients treated with aspirin. The study will not include mild TBI patients who are not eligible for early discharge: patients with no possibility of home supervision, those with a GCS lower than 14 after the CT scan or those treated with anticoagulant/antiplatelet drugs other than aspirin. The investigators expect the TCD-based strategy to be non-inferior compared to the standard strategy according to French recommendations in terms of the 3-months neurological outcome. From a public health standpoint, the use of TCD as a triage tool may change current guidelines regarding mild TBI management.

Clinical Trial Comparing the Efficacy of Two Teletherapy Programs at Improving Psychological Health in People With Brain Injury

The purpose of the study is to test two different training programs to find out which is better at helping people with a concussion or mild TBI (mTBI) improve their emotional health and well-being. Study participation is completely remote and will last approximately 8 months total, involving 4 assessment visits and 8 sessions of brain training via a secure video-conferencing platform. The 4 assessment visits (about 30-90 minutes each) include surveys and questionnaires about participant's emotional health. These assessment visits will take place before the training, immediately after the training, 3 months after training and 6 months after training. The 8 sessions of 1-on-1 training (about 60-90 minutes each) will be completed over the course of approximately 1 month.

Personalized Brain Stimulation to Treat Chronic Concussive Symptoms

The goal of this study is to investigate a new treatment for chronic symptoms after concussion or mild traumatic brain injury in people aged 18-65 years old. Chronic symptoms could include dizziness, headache, fatigue, brain fog, memory difficulty, sleep disruption, irritability, or anxiety that occurred or worsened after the injury. These symptoms can interfere with daily functioning, causing difficulty returning to physical activity, work, or school. Previous concussion therapies have not been personalized nor involved direct treatments to the brain itself. The treatment being tested in the present study is a noninvasive, personalized form of brain stimulation, called transcranial magnetic stimulation (TMS). The investigators intend to answer the questions: 1. Does personalized TMS improve brain connectivity after concussion? 2. Does personalized TMS improve avoidance behaviors and chronic concussive symptoms? 3. Do the improvements last up to 2 months post-treatment? 4. Are there predictors of treatment response, or who might respond the best? Participants will undergo 14 total visits to University of California Los Angeles (UCLA): 1. One for the baseline symptom assessments and magnetic resonance imaging (MRI) 2. Ten for TMS administration 3. Three for post-treatment symptom assessments and MRIs Participants will have a 66% chance of being assigned to an active TMS group and 33% chance of being assigned to a sham, or inactive, TMS group. The difference is that the active TMS is more likely to cause functional changes in the brain than the inactive TMS.

Evaluation of Cognitive Behavioral Therapy for Insomnia (CBT-I) in Individuals With Mild Traumatic Brain Injury (mTBI)

This study will employ cognitive behavioral therapy for insomnia (CBT-I) among individuals with mild traumatic brain injury (mTBI) who experience sleep disturbances. The research aims to evaluate the effects of CBT-I on sleep, mTBI symptoms, and, in particular, the ability of individuals with mTBI to engage in their desired daily life activities. The main questions this study aims to answer are: 1. Does CBT-I positively impact symptoms of mTBI? 2. Does CBT-I improve functional performance in individuals with mTBI?

Non-invasive Stimulation of the Glymphatic System for Slowing Cognitive Decline

The purpose of this research is to demonstrate that mild stimulation of a nerve (trigeminal nerve) in the head can modulate blood flow in the brain. The modulated blood flow will restore the flow of cerebrospinal fluid (CSF) and this in turn can help improve waste clearance in the brain and prevent build up that may lead to disease.

Post-Concussion Differences Between Buffalo Concussion Treadmill Test (BCTT) and Modified Dynamic Exertion (mEXiT) Test

This study aims to compare symptom provocation, physiologic response, and rate of perceived (RPE) between the Buffalo Concussion Treadmill Test (BCTT) and a Modified Dynamic Exertion (mEXiT) test after sport related concussion in adolescents aged 14-17. Participants will be enrolled at their initial concussion clinical visit within 14 days of their injury, and randomly assigned to either the BCTT or mEXiT group. Participants will complete a single visit.

Neuromodulation and Neuroimaging in Older Children With Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) often causes persistent motor and cognitive deficits in children resulting in functional limitations. We are testing a brain stimulation method along with evaluating objective tools to help record and restore communication among affected brain areas, which will facilitate recovery in youth after mTBI.

Passive Neurosensory Reintegration Training as a Tool to Augment Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) poses a substantial clinical and public health burden, often leading to persistent neurosensory and cognitive symptoms for which diagnostic and therapeutic solutions remain limited. This study proposes a multimodal diagnostic framework that integrates established mTBI screening tools and clinical neuro-optometric assessments with high-resolution oculomotor, vestibular, and reaction time (OVRT) testing to enhance diagnostic precision and identify prognostic markers of recovery. Normative data will be established in healthy controls to inform objective thresholds and support clinical implementation. Concurrently, we will evaluate the safety, tolerability, and preliminary efficacy of a novel, minimal-risk multisensory therapeutic intervention (i.e., passive neurosensory reintegration training, or PNRT) for individuals with sub-acute or chronic mTBI. By addressing critical gaps in both diagnosis and treatment, this project will improve mTBI recovery outcomes, inform future clinical trials, and advance evidence-based mTBI care guidelines.

Multicenter Early Intervention Study in Adults With Complaints After Mild Traumatic Brain Injury

Rationale: In the Netherlands, traumatic brain injury (TBI) is one of the most frequent neurological diseases and one of the leading causes of disability. Presumably, about half of the total Dutch population will get a TBI during their lifetime. The majority, about 85%, of patients suffers from a mild TBI (mTBI). The incidence of mTBI is estimated at 68,000 patients each year, but this is an underestimation as patients seen at the general practitioner's offices are not taken into account. In general, the prognosis of mTBI is relatively good, however more than 70% of patient still have one or more post-traumatic complaints at six months post-injury influencing resumption of daily (social) activities and return to work/study. Considering the high annual incidence of mTBI the number of patients with incomplete recovery has high social impact accompanied with excessive health care related costs. Post-traumatic complaints in the chronic phase postinjury are considered therapy resistant and so far no evidence based treatment is available. Hence, the most appropriate strategy is to prevent complaints present in the (sub)acute phase after injury to become persistent to improve functional outcome and quality of life. Objective: The main aim of this study is to improve early care for patients suffering from post-traumatic complaints after mTBI through the development of effective symptom-guided tailored interventions. Nowadays, no effective therapy is available and care-as-usual consists of a wait-and-see policy. Early therapy will reduce posttraumatic complaints and facilitate earlier return to daily activities and work or study, consequently quality of life will be improved as well. This in turn will result in less healthcare consumption and lower societal costs. Study design: The investigators propose a prospective three-arm multicenter open randomized controlled trial (RCT), randomizing participants between two interventions and care as usual. The end-point assessment is blinded. Study population: Adults, aged 18-70 years, diagnosed with a mTBI at the Emergency Department (ED) of the participating hospitals within 24 hours after injury are eligible for inclusion. Intervention: At two weeks post-injury the presence, severity, and type of post-traumatic complaints are assessed using the Rivermead Postconcussive complaints Questionnaire (RPQ). If a predefined minimum of complaints is present, a participant is randomised for one of the two interventions or the control group. The first intervention arm consists of symptom-targeted treatment with assignment to physical and/or occupational therapy. The second intervention arm involves psychoeducation about the complaints through telephonic counselling. The interventions are offered during three weeks from week 3-6 week post-injury. Main study parameters/endpoints: The primary outcome measure is the total RPQ sum score at three months postinjury. The secondary outcome measures are functional outcome and quality of life. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants included in treatment arm 1 will undergo three to six therapy sessions with a physiotherapist and/or occupational therapist over a period of three weeks. This regimen may be potentially burdensome by its frequency but the risks associated with these treatments are low. Participants randomised to treatment arm 2 will receive three telephone calls over the course of three weeks, during which psychoeducation will be provided. This intervention is minimally burdensome and risk-free. All participants included in the interventional part of the study will complete questionnaires at three time points after injury and will receive two follow-up telephone calls three and six months post-injury for outcome assessment. This process is minimally burdensome and poses no risk. Finally, participants included in the registry will complete a limited set of questionnaires at three time points, which is also minimally burdensome and riskfree.

Crisis Response Planning in Military Personnel With Mild Traumatic Brain Injury

The study purpose is to test the effect of Crisis Response Planning (CRP) when used as the second method of suicide prevention in military service members who are at risk for suicide due to mild traumatic brain injury (mTBI). CRP will be compared to usual treatment. The treatment will be a 30 to 60 minute session to one person at a time either in-person or using telehealth.

Behavioral Insomnia Treatment in Mild Traumatic Brain Injury

This is a single site, two-armed random controlled trials (RCT) comparing six sessions of Cognitive Behavioral Therapy for Insomnia (CBT-I) with four sessions of Brief Behavioral Therapy for Insomnia (BBT-I) in service members with comorbid insomnia and prolonged postconcussive symptoms present for at least 3 months after Mild Traumatic Brain Injury (mTBI).

Pilot rTMS for AUD+mTBI

This is a pilot randomized controlled trial (RCT) for Veteran participants with alcohol use disorder co-occurring with mild traumatic brain injury and/or post-traumatic stress disorder. The treatment intervention is repetitive Transcranial Magnetic Stimulation (rTMS) and the goal is to reduce alcohol craving with this treatment. The study will enroll 20 Veteran participants. Half of these participants will receive real rTMS and half of the participants will receive placebo rTMS. rTMS treatment will be provided over 10 sessions that will occur once every weekday for 2 weeks. Veteran participants will then complete follow-up phone calls to further evaluate alcohol craving and other symptoms.

Vestibular Rehabilitation App for Adults With Dizziness Related to mTBI

The goal of this clinical trial is to compare outcomes for standard vestibular rehabilitation home program to a digital vestibular rehabilitation home program in adults with dizziness related to mild traumatic brain injury (mTBI). The main question is whether participants who use the digital format of vestibular rehabilitation improve to a greater extent at discharge than those who use the standard format. Participants will undergo a customized vestibular rehabilitation home exercise program per standard of care, consisting of gaze stabilization, habituation, balance and gait exercises, and endurance training under the supervision of a physical therapist. Participants will complete the gaze stabilization and habituation exercises 2-3 times per day and the balance and gait exercises 1 time per day for 4 weeks. Participants will be tested before and after the 4-week intervention. At the initial session, the researcher will perform standard clinical tests of the inner ear balance system. Also at the initial session, the researcher will perform standard clinical tests of balance and walking and questionnaires about the impact of dizziness on daily activities. At the final session, the researcher will repeat the tests of balance and walking and questionnaires. Three months after completing the intervention participants will complete an online questionnaire about the impact of dizziness on daily activities.

Pilot Study of Neurofeedback for Photosensitivity in Mild Traumatic Brain Injury

The goal of this study is to complete a pilot study testing the feasibility and acceptability of low-intensity pulse-based transcranial stimulation (LIP-tES) neurofeedback intervention for reducing photosensitivity symptoms in Veterans with a history of mild traumatic brain injury (mTBI). The study will also complete resting-state MRI scans to assess neurophysiological markers of photosensitivity and changes associated with LIP-tES intervention.

Auditory Plasticity Training

The investigators are working on a project to help people who have had mild brain injuries hear better. Sometimes, these injuries can make it hard for people to hear clearly, especially in noisy places or when trying to tell where sounds are coming from. The project is testing special training exercises that have helped healthy people improve their hearing in these situations. The goal is to see if these exercises can also help people with mild traumatic brain injuries (mTBI). If these exercises work, they could help doctors give better treatment to people with hearing problems after a brain injury. This would be especially helpful for soldiers who need to stay ready for duty. It could also make life better for veterans who struggle with hearing issues and help lower the cost of healthcare.

Concussion Recovery and Support Program

Pilot randomized controlled trial (RCT) comparing a novel intervention Concussion Recovery and Support Program (CRISP) for adolescents and young adults (AYA) 18-29 yo with concussion/ mild TBI.

Remotely Supervised tDCS+ for Complex Attention in mTBI (Cognetric)

The proposed study will evaluate a new approach to cognitive rehabilitation of mTBI using a brain stimulation technique called "Remotely Supervised Transcranial Direct Current Stimulation combined with Cognitive Training" (RS-tDCS+) which has shown promise for improving complex attention in both healthy and clinical populations. RS-tDCS+ is a home-based, low-risk, non-invasive technique that is designed to boost cognitive training by enhancing learning and the brain's ability to reorganize connections. This study will evaluate RS-tDCS+ for improving complex attention in Active Duty Service Members (ADSM) and Veterans with a history of mTBI. Different tests of complex attention and symptom questionnaires will be used to determine the effects of real versus sham (placebo) RS-tDCS+. Second, the investigators will investigate electrical and connectivity changes in the brain associated with RS-tDCS+ using electroencephalogram (EEG) and magnetic resonance imaging (MRI). Third, the investigators will investigate the lasting effects of any observed changes by evaluating participants at 1 and 6 weeks post-treatment. Lastly, the investigators will explore the impact of individual differences (e.g., PTSD, depression, sleep quality, time since injury, baseline impairment, age, sex, ADSM versus Veteran) on treatment outcome.

Utilizing Electronic Clinical Decision Support to Enhance mTBI Care at the Primary Care Point of Entry

Six primary care practices within a large Philadelphia pediatric care network will use an electronic Clinical Decision Support (eCDS) tool as standard care for concussion evaluation. The eCDS tool will include a prediction rule for children aged 5-18 assessed for mild traumatic brain injury (mTBI). The eCDS tool predicts risk for persistent symptoms and prompts referral to specialty care for those deemed high risk. This research proposes to analyze the clinical and process outcomes in these six practices relative to the rest of the care network, specifically, whether the eCDS tool reduces time to symptom resolution.