73 Clinical Trials for Various Conditions
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.
This protocol is for an open-label randomized trial evaluating the safety of using ketamine in combination with propofol for sedation versus the standard of care analgosedation in patients admitted to the intensive care unit with severe traumatic brain injury.
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.
The main goal of this clinical trial is to check if the treatment is safe and well-tolerated. Researchers will compare the MR-301 active drug group with the placebo group to evaluate the safety and tolerability of the drug. Other measurements include assessing the patient's overall outcome, neurological responses, time spent in the intensive care unit, time in the hospital, and mortality. Participants will receive either MR-301 BID IV dosing or a matching placebo for a total of 3 weeks.
Traumatic brain injury (TBI) accounts for approximately 2.5 million visits to emergency departments in the United States each year. After decades of research, management strategies for severe TBI (sTBI) patients are still evolving. Optimizing intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are paramount in the management of these patients and placement of these monitors is the current standard-of-care. However, monitoring brain oxygenation (PbtO2) with invasive intraparenchymal monitors is currently under investigation in the management of severe TBI and placement of these monitors is gaining widespread use. This has opened the door for the use of tiered therapy to optimize ICP and PbtO2 simultaneously. Current evidence indicates that correction of ICP, CPP and PbtO2 in sTBI requires optimized analgesia and sedation. Ketamine is one of the few drugs available that has both sedative and analgesic properties and does not commonly compromise respiratory drive like opioids and sedative-hypnotics. However, traditionally, ketamine has been viewed as contraindicated in the setting of TBI due to concerns for elevation in ICP. Yet, new data has cast this long-held assumption into significant doubt. Hence the present pilot study will characterize the neurophysiological response to a single dose of ketamine in critically-ill TBI patient with ICP and PbtO2 monitoring.
After injury, survivors of msTBI depend on informal family caregivers. Upwards of 77% of family caregivers experience poor outcomes, such as adverse life changes, poor health related quality of life, and increased depressive symptoms. Caregivers frequently report minimal support or training to prepare them for their new role. Periods of care transitions, such as ICU discharge, are most difficult. The majority (93%) of previously developed caregiver and caregiver/survivor dyad interventions after msTBI focus on providing information or practical skills to either survivors, or to long-term caregivers (\>6 months post injury), rather than education, support, and skill-building that the new caregiver may use proactively that will benefit the dyad acutely after injury. The Aims of this proposal are to: (1) Determine feasibility, satisfaction, and data trends of CG-Well; and (2) Understand how baseline psychosocial risk factors affect response to CG-Well compared to an Information, Support, and Referral control group. To accomplish this, I will first enroll 6-10 caregivers and tailor CG-well until each finds the intervention acceptable, appropriate, and feasible. I will then enroll 100 (50/group) dyads and determine satisfaction ratings, recruitment, retention, and treatment fidelity of CG-Well. Additionally, I will determine if caregivers report reductions in depressive symptoms and improvements in life changes as a result of improvements in task difficulty and threat appraisal in CG-Well compared to ISR at six months. Information obtained in Aims 1 and 2 will be used to plan a larger Phase III trial of CG-Well. Completing these Aims and the training plan will improve outcomes of caregivers and downstream outcomes of survivors of msTBI, and provide me with the skillset necessary to become an independent researcher who can develop and test high-impact, high-fidelity, sustainable interventions.
The purpose of this study is to evaluate the effectiveness of nebulized lidocaine before Endotracheal suctioning (ETS) compared to instilled lidocaine and the effectiveness of aerosolized lidocaine versus instilled normal saline before ETS in attenuating the increase of intracranial pressure (ICP) in severe head injured children and to evaluate the feasibility of a trial involving instilled lidocaine and aerosolized lidocaine for the management of ETS and to evaluate the safety of nebulized lidocaine in traumatic brain injury (TBI) compared to instilled lidocaine and instilled sodium chloride (NS).
This study aims is to describe the pharmacokinetic properties of levetiracetam through measurement of serum concentrations in critically ill, severe traumatic brain injury patients.
BioBOOST is a multicenter, observational study of the effect of derangements in brain physiologic parameters on brain injury biomarker levels in patients with severe traumatic brain injury.
Traumatic Brain Injury (TBI) represents a significant public health risk in the United States leaving many survivors with significant long term cognitive deficits and at risk for neurodegenerative diseases. Despite extensive research there are no pharmacological therapies which have demonstrated significant improvement in neurological or cognitive recovery. Changes in glucose metabolism are considered the hallmark metabolic response to TBI and ketosis has been proposed as a therapy to ameliorate metabolic dysfunction. This trial investigates the therapeutic potential of a ketogenic or modified Atkins diet on neurocognitive outcome following moderate-severe TBI.
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.
Cognitive behavioral therapy for major depressive disorder (MDD) was adapted for individuals with moderate to severe traumatic brain injury (TBI) (CBT-TBI). A structured, treatment manual was developed. The primary aim is to evaluate the acceptability and tolerability of, and adherence to, CBT-TBI in a randomized waitlist-controlled, 12-week pilot trial (N=40). The exploratory aim is to evaluate the potential efficacy of CBT-TBI for MDD in the randomized pilot trial (N=40) and possible moderators and mediators of outcome.
Metacognition, in-the-moment awareness of performance while engaging in cognitive tasks, is negatively affected by traumatic brain injury (TBI). Metacognitive deficits can greatly reduce quality of life for individuals with TBI as functioning in this domain has been closely linked with successful independent living and community re-integration. Problematically, there are currently no empirically validated treatment options that address metacognitive deficits after TBI. Recent research in healthy samples demonstrates that specific listening interventions may alter neural activation in brain works associated with metacognition and can improve metacognitive functioning; however, it remains unknown if these effects generalize to individuals with TBI. Thus, the objective of the proposed study is to use a double-blind, placebo controlled randomized clinical trial to determine the efficacy of applying a specific listening intervention to improve metacognition after TBI and to employ functional magnetic resonance imaging (fMRI) to document the neural mechanisms by which the intervention operates.
The investigators will conduct an observational crossover study. The investigators aim to recruit 50 participants with severe Traumatic Brain Injury (TBI) requiring intracranial pressure (ICP) monitoring during their stay at the Neuro Trauma ICU at the R Adams Cowley Shock Trauma Center. Overall, participants will be monitored, on average, for approximately 6-8 hours during the study period. The investigators do not anticipate the need for prolonged monitoring during the duration of their hospital stay or post hospital period.
Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the US. The CDC states that 1.7 million people sustain a traumatic brain injury each year, with death occurring in 52,000 of these injured patients. It is also estimated that 275,000 yearly require hospitalization. The costs of TBI can be devastating to our society, with the 2010 economic cost estimated to be approximately $76.5 billion. 90% of this cost involves fatal or hospitalized brain injured patients. Furthermore, survivors of traumatic brain injury have high rates of institutionalization, readmission, and disability. The prediction of prognosis in severe TBI is a difficult problem for physicians. Prognosis evaluation in the acute phase of care varies widely among physicians caring for these patients\[3\]. With prognosis often in doubt, physicians have difficulty leading families and patients toward the most appropriate treatment which often leads to expensive testing and patient management. The Brain Trauma Foundation has recommended several early indicators of prognosis in severe TBI, including age, hypotension, CT scan features, Glasgow Outcome Scale score, and pupillary diameter with light reflexes. Pupillary diameter and light reflexes have been extensively studied, however accurate measurements of these prognostic factors have not been performed due to a lack of standardized measuring procedure. A new device has been validated to measure both pupil size and reactivity using infrared pupillometry. This device has also been studied to create the Neurological Pupil Index (NPi) as a measure of pupillary reactivity. The NPi has been shown to correlate with intracranial pressure readings, however there are no studies correlating the pupillometer findings with outcome measures in TBI. This study will prospectively evaluate the pupillometer readings of pupillary size and reactivity (NPi) to test the hypothesis that the NPi is a realiable predictor of 30-day outcomes in patients with severe TBI.
Pediatric severe traumatic brain injury (TBI) is the leading cause of death and disability in children ages 1-14 years old. There are no effective therapies to treat secondary brain injury and the post-injury response of CNS apoptosis and neuroinflammation. This study is a follow-up trial from a previously performed Phase I trial that demonstrated the safety and potential CNS structural preservation effect of intravenous autologous bone marrow mononuclear cells (BMMNC) after severe TBI in children. (Cox, 2011) The study is designed as a prospective, randomized, placebo controlled, blinded Phase 2 safety/biological activity study. The investigators hope to determine the effect of intravenous infusion of autologous BMMNCs on brain structure and neurocognitive/functional outcomes after severe TBI in children.
The investigators hypothesize that hypothermia (body cooling) and additional magnesium sulfate will improve the outcome of severe Traumatic Brain Injury (TBI) patients. This is a study to compare the outcomes of patients with severe traumatic brain injury who have been allocated to one of the following three groups: Group 1 - Conventional therapy following traumatic brain injury Group 2 - Subjects will have their core body temperature lowered to 34C Group 3 - Subjects will have their core body temperature lowered to 34C and will receive a supplemental intravenous infusion of magnesium sulfate.
The SyNAPSe trial will study if giving intravenous (i.v.) progesterone within 8 hours of the injury for a total of 120 hours to severe traumatic brain injury patients improves their recovery.
The aim of this study is to assess the safety and feasibility of dexmedetomidine as an adjunct to conventional sedative therapy compared to conventional sedative therapy alone in patients with severe traumatic brain injury.
This is a controlled trial of amantadine to improve level of function following severe traumatic brain injury. The purpose of this study is: 1. To determine whether amantadine hydrochloride, given in a dose of 200-400 mg, improves functional recovery from the vegetative and minimally conscious states 2. To determine whether amantadine-related gains in function persist following drug discontinuation 3. To determine the safety profile of amantadine in patients with disorders of consciousness
The investigators plan to utilize conivaptan (Vaprisol) to promote isolated water loss, in combination with normal (physiologic) fluid replacement to maintain a normal blood volume status, in patients with severe TBI. The goal of this therapy is to raise blood sodium in a controlled fashion in subjects with severe TBI, and reduce the use of hypertonic saline infusion. We hypothesize that this therapy will maintain a stable state of high blood sodium, while decreasing the overall sodium load needed to achieve these goals.
The purpose of this study is to determine if hypertonic saline with and without dextran can improve neurologic outcomes in victims of severe traumatic brain injury (TBI). Injury and lost blood from trauma can cause your body to go into shock (low blood pressure related to blood loss). This decreased blood flow can lead to organ damage. In order to restore the blood pressure and blood flow, the medics give fluids into the patients' veins as soon as possible. This is called "resuscitation". The fluid most commonly used is "isotonic" or one that is the same salt concentration as the blood. The investigators are trying to determine if infusing a "hypertonic" fluid or one more concentrated than the blood can increase the blood pressure and restore blood flow more efficiently. The hypertonic fluids they are using are called hypertonic saline with dextran (HSD) and hypertonic saline (no dextran). Hypertonic saline is a salt solution that is slightly more concentrated than blood. Dextran is a sugar solution.
The goal of this phase 1 randomized controlled safety and feasibility clinical trial are to determine the safety of external lumbar drainage (ELD) in select patients with severe Traumatic Brain Injury (TBI). The main questions it aims to answer are (i) if ELD is feasible and (ii) safe to perform in severe TBI patients who have radiological evidence of patent basal cisterns and midline shift \<5mm without increasing the risk of neurological worsening or cerebral herniation. All participants will receive routine usual care. The study group will additionally have ELD for cerebrospinal fluid (CSF) drainage. A comparison will be made between the usual treatment plus ELD (interventional) groups, and the usual treatment (control) groups on incidence rate of neurological worsening or cerebral herniation events, and whether total hours with raised intracranial pressure (ICP) are different.
Narrative: Worldwide, traumatic brain injury (TBI) is a leading cause of death and disability among children and adolescents. The Investigators aim to test whether pediatric TBI treatment guided by invasive intracranial pressure monitoring produces better patient outcomes than care guided by a protocol without invasive monitoring. Study findings will inform clinical practice in treating pediatric severe TBI globally. Focused didactic and experience-based learning opportunities will increase the research capacity of pediatric intensivists in Latin America.
Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT) is an international research study designed to evaluate the impact of interventions on the outcomes of children with severe traumatic brain injury. Pediatric traumatic brain injury (TBI) is the leading killer of children, resulting in more than 7000 deaths and $2 billion in acute care costs each year. Despite this large burden of disease, advances in the field have been limited due to weak evidenced-based guidelines and the limitations of randomized, controlled trials (RCTs) to demonstrate efficacy of single treatment strategies due to wide treatment variability. ADAPT is a practical study design in a novel approach - an observational cohort study designed to evaluate the association of 6 aspects of pediatric TBI care with outcomes using statistical modeling to correct for confounding variables. Completion of this study will provide compelling evidence to change clinical practices, provide evidence for new Level II recommendations for future guidelines and lead to improved research protocols that would limit variability in TBI treatments - helping children immediately through better clinical practices and ultimately through more effective investigation.
Traumatic brain injury (TBI) is a major cause of death and disability, with an estimated cost of 45 billion dollars a year in the United States alone. Every year, approximately 1.4 million sustain a TBI, of which 50,000 people die, and another 235,000 are hospitalized and survive the injury. As a result, 80,000-90,000 people experience permanent disability associated with TBI. This project is designed to determine whether a device designed to measure brain tissue oxygenation and thus detect brain ischemia while it is still potentially treatable shows promise in reducing the duration of brain ischemia, and to obtain information required to conduct a definitive clinical trial of efficacy. A recently approved device makes it feasible to directly and continuously monitor the partial pressure of oxygen in brain tissue (pBrO2). Several observational studies indicate that episodes of low pBrO2 are common and are associated with a poor outcome, and that medical interventions are effective in improving pBrO2 in clinical practice. However, as there have been no randomized controlled trials carried out to determine whether pBrO2 monitoring results in improved outcome after severe TBI, use of this technology has not so far been widely adopted in neurosurgical intensive care units (ICUs). This study is the first randomized, controlled clinical trial of pBrO2 monitoring, and is designed to obtain data required for a definitive phase III study, such as efficacy of physiologic maneuvers aimed at treating pBrO2, and feasibility of standardizing a complex intensive care unit management protocol across multiple clinical sites. Patients with severe TBI will be monitored with Intracranial pressure monitoring (ICP) and pBrO2 monitoring, and will be randomized to therapy based on ICP along (control group) or therapy based on ICP in addition to pBrO2 values (treatment group). 182 participants will be enrolled at four clinical sites, the University of Texas Southwestern Medical Center/Parkland Memorial Hospital, the University of Washington/Harborview Medical Center, the University of Miami/Jackson Memorial Hospital, and the University of Pennsylvania/Hospital of the University of Pennsylvania. Functional outcome will be assessed at 6-months after injury.
The primary goal of this project is to demonstrate the feasibility and clinical benefits of a new rapid treatment for secondary treatment for secondary brain injury called Discrete Cerebral Hypothermia System by CoolSystems, Inc., Berkley, CA. This device induced hypothermia in the adult brain without significant whole body hypothermia. Discrete Cerebral Hypothermia System holds a great potential for protecting the brain from the devastating secondary complications of trauma without the associated deleterious system effects.
When fever is present in patients with stroke, traumatic brain injury (TBI), or brain hemorrhage, it has been associated with worse outcomes including larger areas of tissue death, increased length of stay, worse degree of coma, lower ability to function, and higher mortality. Both adult and pediatric TBI national guidelines state that maintenance of normal body temperature should be a standard of care. However, no further standards or options are presented to specifically guide practice. The current ischemic stroke guidelines state that fever should be treated with fever-reducing agents and offer "cooling devices" as an option but do not provide specifics to guide practice. Over 50% of patients in the Neurosurgical Intensive Care Unit (ICU) at Harborview Medical Center develop fever during the course of their stay. With elevated temperatures the body consumes more oxygen than if the temperature was normal, causing less oxygen to be available to the brain. This may lead to injury of the brain cells and a diminished capacity for healing. Thus, temperature management in neurologically vulnerable patients is both a prevalent and problematic challenge. Based on this information the goal of the present proposal is to evaluate if 1) A standardized, step-wise approach to temperature management using a Normothermia Protocol is successful in achieving and maintaining normal temperature in Neurosurgical ICU patients; and 2) If maintenance of normal temperature will be associated with fewer episodes of diminished responsiveness in their neurological exams as evidenced by a measure of depth of coma, as measured by the Glasgow Coma Score (GCS) compared to a control group treated according to usual care.
This study is designed to examine the effects of a wake-promoting agent (Modafinil) on working memory (WM) in persons with moderate to severe TBI utilizing a double blinded placebo controlled methodology. Our approach is to evaluate participants with BOLD fMRI and a limited neuropsychological battery to examine WM performance before and after pharmacological intervention. Hypotheses 1. Because increased cognitive effort (as a function of decreased efficiency after TBI) is presumed to underlie fMRI activation dispersion that is seen during central executive WM tasks, we anticipate an attenuation of cerebral activation in prefrontal cortex during pharmacological intervention with Modafinil when compared to placebo administration on the mPASAT and vigilance testing. 2. There will be a correlation between the decreased dispersion of the fMRI signal on scans and improvement in neuropsychological measures when individuals are on Modafinil that is not seen when they are taking placebo.
Approximately 5.3 million people live with a long-term disability resulting from a traumatic brain injury (TBI) and between 5-8% of those older than 60 suffer from Alzheimer's disease or other forms of dementia (ADRD). Consequences of these conditions can result in dramatic and persistent changes in functioning, impacting not only the patients, but also loved ones who become informal support persons. Many existing services help the family in the moment, but do not address long-term wellness. Thus, the purpose of this research study is to compare the effect of two different types of group wellness treatments for individuals with chronic mild TBI, moderate to severe TBI, and ADRD and their support persons.