46 Clinical Trials for Various Conditions
This is a multicenter, single arm, open label clinical trial that is designed to test the safety and preliminary efficacy of single administration inhibitory nerve cells called interneurons (NRTX-1001), into both temporal lobes of subjects with drug-resistant bilateral mesial temporal lobe epilepsy.
The main goals of this clinical study are to learn if AMT-260 is safe and tolerable and works to reduce the frequency of seizures in adults with unilateral mesial temporal lobe epilepsy (MTLE).
This clinical trial is designed to test whether a single image-guided intracerebral administration of inhibitory nerve cells, called interneurons (NRTX-1001), into subjects with drug-resistant unilateral mesial temporal lobe epilepsy (MTLE), with or without mesial temporal sclerosis (MTS), is safe (frequency of adverse events) and effective (seizure frequency). NRTX-1001 comprises human interneurons that secrete a neurotransmitter, gamma-aminobutyric acid (GABA).
The goal is to provide a novel therapeutic option for temporal lobe epilepsy patients when focal impaired awareness seizures cannot be stopped by medications, surgical or laser ablation, or by neurostimulation. The goal is restore consciousness when seizures cannot be stopped. If successful, addition of bilateral thalamic stimulation to existing responsive neurostimulation to rescue consciousness would greatly alter clinical practice and patient outcomes. Importantly, previous approaches aim to stop seizures, whereas this study aims to use thalamic stimulation to improve a major negative consequence when seizures cannot be stopped. The potential impact extends beyond temporal lobe epilepsy to other seizure types, and may also extend more broadly to inform treatment of other brain disorders associated with impaired consciousness and cognition.
The 24/7 EEG™ SubQ system will be compared to simultaneously recorded video-EEG in the Epilepsy Monitoring Unit (gold standard) and to self-reported seizure log books throughout 12 weeks of outpatient EEG recording. The present study is a 12-week open-label, prospective study with a paired, comparative design for pivotal evaluation of the safety and effectiveness of the 24/7 EEGTM SubQ system in subjects with epilepsy involving the temporal lobe region . 2-5 sites in Europe Up to 10 sites in US
The investigators will conduct a tau PET scan in cognitively normal older adults and patients with Mild Cognitive Impairment (MCI), enrolled in the National Alzheimer's Coordinating Center (NACC) study at the University of Pennsylvania's Penn Memory Center/Alzheimer's Disease Core Center (PMC/ADC).
Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes. During a typical four-week ECT series, most depressive episodes will respond to treatment and people will improve their level of functioning (return to work or family). Independent of the antidepressant effect of ECT, many patients experience transient memory impairment. This investigation will examine the impact of one ECT parameter (pulse amplitude or current) on brain changes (structure of connections within the brain) and clinical outcomes. The goal of this investigation is to determine the optimal parameter for an individual patient that will maintain the clinical response (reduce depression severity) and minimize side effects (eliminate memory issues related to treatment).
The study is designed to evaluate the safety and efficacy of the Visualase MRI-guided laser ablation system for mesial temporal epilepsy (MTLE).
The primary aim of the current proposal is to evaluate safety and tolerability, in terms of neuropsychological effects of low frequency electrical stimulation of the fornix (LFSF) in participants with medically-intractable Mesial Temporal Lobe Epilepsy. Secondary aims include evaluation of psychiatric changes, seizure frequency, and quality of life during LFSF.
Memory difficulty ranks among the most common complaints for patients with temporal lobe epilepsy. While these cognitive problems may affect quality of life more than seizure frequency, no effective therapy exists. Transcranial Direct Current Stimulation (tDCS) is a method of safe, noninvasive, and painless brain stimulation delivering low intensity direct current through scalp electrodes to modulate brain activity. Several recently published studies demonstrate the enhancement of working memory and mood with stimulation of the frontal region of the brain. Furthermore, tDCS has never been reported to have induced a seizure. The aim of our study is to determine whether real tDCS can improve memory function and mood. The investigators are enrolling patients with well-controlled temporal lobe epilepsy who have not undergone brain surgery.
We intend to use focused ultrasound to stimulate or suppress brain activity in patients with epilepsy. We hypothesize that focused ultrasound is capable of brain stimulation or suppression visible with functional MRI, and will not cause tissue damage.
Background: - Some people with epilepsy have an epileptic focus, a small part of the brain that is the starting point of the seizure. This focus is like an irritant or an inflammation, and helps cause the seizure. People with epilepsy that affects the temporal lobe of the brain often have an epileptic focus. Researchers want to look at the epileptic focus by using a drug that attaches to a protein associated with inflammation. An imaging study with the drug will show how much inflammation is in the area of the brain where the seizures start. The drug, called \[11C\]DPA-713, will be tested for its effectiveness in people with temporal lobe epilepsy. Its effects will be compared with imaging studies given to healthy volunteers. Objectives: - To see if \[11C\]DPA-713 can show the inflammation in the epileptic focus of seizures. Eligibility: * Individuals at least 18 years of age who have temporal lobe epilepsy. * Healthy volunteers at least 18 years of age. Design: * Participants will have three outpatient visits to the National Institutes of Health Clinical Center. The visits will last from 2 to 5 hours. * Participants will be screened with a physical exam, neurological exam, and medical history. Blood samples will be collected before the start of the study. * Participants will have a positron emission tomography (PET) scan. This scan will be used to look at brain chemistry and function. The study drug will be given during the scan to see how well it shows points of inflammation in the brain. Some participants will provide additional blood samples during the PET scan. * Participants will also have a magnetic resonance imaging (MRI) scan. This scan will look at the structure of the brain.
Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Pilot data shows that GABA(A) binding potential and glutamate utilization are tightly coupled in healthy subjects particularly in the mesial temporal lobe. We hypothesize that subjects with epilepsy will not exhibit the same degree of coupling, and that subjects with both epilepsy and depression will exhibit an even more pronounced decoupling. Study Population: Subjects aged 18-55 with localization-related epilepsy with and without depression, subjects with generalized epilepsy, subjects with major depressive disorder (MDD) alone, and healthy controls. Design: This is a neuroimaging study, using positron emission tomography (PET) with \[11C\]flumazenil, to measure GABA(A) binding potential, and \[18F\]fluorodeoxyglucose, to measure glucose utilization (reflective of neuronal glutamate release) Magnetic resonance spectroscopy (MRS), will be used to measure GABA and glutamate in the mesial temporal cortex, and corroborate the PET results. Structural magnetic resonance images (MRI) will be obtained for MRS localization and partial volume correction of PET images. Outcome measures: The binding potential of GABA(A), the regional rate of glucose metabolism, and the levels of GABA and glutamate as measured by MRS. Patients will be stratified by seizure type and depression ratings. ...
This is a research study evaluating the use of escitalopram (Lexapro®) for the treatment of major depression in subjects with temporal lobe epilepsy. The purpose of the study is to measure the severity and change in depressive and anxiety symptoms after 10 weeks of study treatment with escitalopram or placebo as measured by certain rating scales and questionnaires. In addition, the study will measure the frequency of seizures using a patient diary during the study. Finally, the study will assess the change in the quality of life using rating scales.
This study uses functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to examine how the brain processes tasks involving language and emotion in normal volunteers and in patients with epilepsy. MRI is a diagnostic and research tool that uses a strong magnetic field and radio waves to obtain images of body organs and tissues. The MRI scanner is a metal cylinder surrounded by a magnetic field. During the test, the subject lies on a table that can slide in and out of the cylinder. DTI involves taking pictures of the brain while the subject is at rest in order to learn about the structure of the brain. Information gained from this study will help scientists evaluate the organization of language and emotional functions in the brain. Normal volunteers and patients with temporal lobe epilepsy 18 years of age and older who are native English speakers and who will undergo surgery for uncontrolled seizures may be eligible for this study. Candidates are initially screened by telephone, then with physical and neurologic examinations and cognitive testing. The study has two parts, conducted 6 to 12 months apart. Each part consists of the same sets of tests described below, using fMRI and DTI. In patients with epilepsy, Part 1 is scheduled before surgery and Part 2 after surgery. * fMRI: Subjects are asked to perform two types of tasks while they undergo fMRI. In one task, they are shown pictures of animals and tools and are asked to name them. In a second task, they are shown pictures that range in content from sexually explicit material, to human injury and surgical slides, to pleasant images of children and wildlife and are asked to decide whether they find the pictures pleasant, neutral, or unpleasant. * DTI: Subjects relax and remain still in the MRI scanner for about 45 minutes. * Neuropsychological testing: Subjects may be asked to complete questionnaires, take pen-and-paper or computerized tests, and perform motor tasks. Participants may be asked to repeat the MRI studies, but not the neuropsychological tests, up to four times to investigate different brain functions or to confirm findings.
The aim of this pilot study is to understand hippocampal network function in mesial temporal lobe epilepsy (MTLE) and to test whether transcranial magnetic stimulation (TMS) targeting the network of the hippocampus can change hippocampal-dependent memory task performance and epileptic activity in people with (MTLE). Positive findings would implicate the hippocampal network as a source of these typical primary MTLE symptoms. Subjects with a primary diagnosis of MTLE will be enrolled in a non-randomized, non-blinded pilot experiment to test target engagement and preliminary efficacy of a novel neurostimulation approach targeting the hippocampal network. At baseline, subjects will undergo neurocognitive testing for hippocampal-dependent memory and functional magnetic resonance imagining (fMRI) neuroimaging assessment of brain structure and task-dependent activity. They will also receive scalp-electroencephalography (EEG) to measure interictal epileptiform discharge (IED) frequency at baseline, and will complete a seizure diary for one month. They will then receive high-frequency repetitive TMS targeting an area of parieto-occipital cortex defined based on fMRI connectivity with the hippocampus measured at baseline. The baseline assessments will then be repeated, using an alternate form of the memory test. The investigators will analyze changes from baseline in memory task performance, fMRI activity of the hippocampal network, IED frequency, and reported seizure frequency.
In this study, participants will receive unilateral Deep Brain Stimulation (DBS) for treatment of epilepsy, with network-based stimulation targets specifically defined using a stereo-electro-encephalographic evaluation and chronic recordings using the Medtronic Percept™ primary cell (PC) Neurostimulator DBS System with BrainSense™ Technology. The hypothesis is that, compared to no stimulation or to standard duty cycle high frequency stimulation, epilepsy neuromodulation using low frequency stimulation and informed by network architecture in patients with epilepsy that arises in a hippocampus that also subserves memory - epilepsy in a precious hippocampus (EPH) - will result in a significant decrease in seizure frequency and severity, paralleled by a decrease in EEG spike counts and improved memory function.
Nearly 100 million Americans are affected by neurological disorders with an overall cost above $765 billion for the more prevalent conditions. Given this significant burden, effective treatments to prevent dementia and new disease modifying therapies are urgently needed. Regeneration of lost neurons with new ones (i.e., neurogenesis) is compromised at early stages of dementia and in part correlates with cognitive impairment in Alzheimer's disease. Boosting the neurogenesis delays the cognitive impairment in animal models of dementia and has been proven beneficial in improving the memory in rodent studies. Aerobic exercise is the most potent known stimulator of neurogenesis in animal models. A crucial next step is to translate endogenous regenerative strategies to people. The purpose of this study is to demonstrate the feasibility and investigate the effects of an exercise program on neurogenesis and cognitive improvement in epilepsy patients.
The investigators plan to enroll individuals with medical temporal lobe epilepsy who are undergoing surgical workup with clinically implanted intracranial electrodes. The study intends to administer computerized memory tasks and stimulation during the intracranial Electroencephalography (EEG) monitoring period.
Mesial temporal lobe epilepsy (MTLE) is the most common cause of medication-resistant epilepsy in adults, and MRI-guided laser interstitial thermal therapy is a new approach to its surgical management; however, while LITT demonstrates fewer complications than traditional surgical techniques, it generates lower rates of seizure freedom. During traditional temporal lobectomy for MTLE, neurophysiologic intraoperative monitoring (NIOM) can be used to better identify epileptogenic tissue and guide resection. Our study proposes to investigate the utility of NIOM during LITT for MTLE. Subjects will be drawn from refractory mesial temporal lobe epilepsy patients determined to be candidates for LITT. During their LITT surgery, in addition to the placement of the stereotactic LITT probe, subjects will receive a second smaller stereotactic electrode for intraoperative monitoring of epileptic discharges before and after surgery. After surgery, at regularly scheduled follow-ups, patients will receive the Quality of Life in Epilepsy questionnaire (QOLIE-31-P), in addition to standard post-operative care. Endpoints will be surgical complications, fractional decrement in epileptiform discharges from pre- to post-ablation recordings, and surgical outcome at 6 months and one year. Analysis of severe complications will be expressed as a simple complication rate, for overall complications, severe complications, and hemorrhagic complications in specific. The relationship between fractional discharge decrement and outcome will be assessed by regression analysis. Risks of the study will stem from the placement of the stereotactic electrode for intraoperative monitoring, which represents a small incremental risk beyond typical LITT for MTLE.
The overall goal of this study is to open up the promising treatment of repetitive transcranial magnetic stimulation (rTMS), which has been shown to be effective against seizures in patients with surface neocortical foci, to a much larger population of patients with mesial temporal lobe epilepsy (MTLE) and other forms of epilepsy with deep foci, who are not currently considered good rTMS candidates. The investigators hypothesize that rTMS can modulate the hyperexcitable state in patients with deep seizure foci by targeting its usage to accessible cortical partner regions. In this study the investigators aim 1) to map the functional connectivity of the epileptogenic mesial temporal lobe in patients with medically refractory mesial temporal lobe epilepsy; and 2) to perform a randomized controlled assessment of repetitive transcranial magnetic stimulation protocols applied to specific neocortical targets in mesial temporal lobe epilepsy. The methods used in this study will include magnetic resonance imaging (MRI) of the brain, electroencephalography (EEG), and transcranial magnetic stimulation (TMS).
OBJECTIVES: About 15% of patients suffering from focal epilepsy are refractory to available pharmacological treatments. Until now, the only hope for such patients has been the development of new pharmaceutical treatments or epilepsy surgery. In case of inoperability, different types of invasive brain stimulation such as vagus nerve stimulation or deep brain stimulation or non-invasive repetitive TMS have been evaluated to determine their anticonvulsive potential. For rTMS, weak and short lasting seizure reduction has been reported in different epilepsy syndromes. A new, non-invasive stimulation technique, transcranial direct current stimulation (tDCS), was useful to modulate cortical excitability in many cortical areas (M1, visual cortex, frontal cortex). Cathodal tDCS, with a current of 1 mA, induced long-term depression in animal models and reportedly decreased the excitability of both human and animal cerebral cortex. In epilepsy patients suffering from a malformation of cortical development, a single session of cathodal tDCS helped reduce seizures briefly. The purpose of this protocol is to study the effects of repeated applications of tDCS on the excitability of the seizure focus in patients with poorly controlled pharmacologically refractory temporal lobe epilepsy. STUDY POPULATION: We plan to study 56 patients between the ages of 18 and 80 suffering from temporal lobe epilepsy. DESIGN: Subjects will be allocated by blocked randomization to one of two groups (parallel design). Group A will receive cathodal tDCS and group B will receive Sham-tDCS on five consecutive days. Each subject will participate in 9 sessions (1 baseline visit, 5 intervention visits, 3 follow-up visits). The effect of the intervention relative to the sham stimulation will be evaluated by comparing seizure frequency and neuropsychological tests during the 8 weeks before and after the intervention. OUTCOME MEASURES: Primary outcome measure will be the mean seizure frequency per 4 weeks in the tDCS group as compared to the Sham-tDCS group. To analyze the effect of the intervention (tDCS), seizures will be evaluated during a 2x4 week baseline period before tDCS and 2x4 weeks after the intervention. Using these data we will calculate the percentage change of seizures per 4 weeks. Secondary outcome measures will be the scores of the neuropsychological testing (HVLT-R, BVMT-R, CTMT, COWAT) and number of epileptiform discharges in the EEG. Furthermore, th...
This study will use light scattering spectroscopy (LSS) to analyze brain tissue removed from patients during brain surgery to determine if this new technology can be used to differentiate between normal and cancerous cells. LSS focuses light on cells or tissues, and the way that light is reflected back from the tissues provides information about the size of cells and the density of the cell nuclei (the part of the cell that contains the genes). Patients between 18 and 75 years of age with a known or suspected brain tumor and patients with temporal lobe epilepsy that does not respond to medication may be eligible for this study. (Examination of tissue from patients with epilepsy will allow comparison of tumor and non-tumor brain cells.) All patients must require surgery to treat their condition. Participants will be admitted to the Clinical Center for 3 to 10 days for physical and neurological examinations, blood and urine tests, and other tests needed to prepare for surgery. They will then undergo surgery. A small amount of tissue removed during surgery for pathological review will be collected for use in this study. Half of the tissue will be examined using LSS to help determine the size of the cell and its nucleus. Studies will be done to measure how many of the cells are actively dividing and which proteins are expressed more often in tumor cells compared with normal cells. This information may shed light on how tumor cells are different from normal cells. Participants may be contacted for up to 3 years to follow their health status.
Repetitive transcranial magnetic stimulation (rTMS) may be able to provide a moderately detailed localization of language functions in the brain. We propose to test the ability of rTMS to locate the substrate of visual naming to a limited area of the temporal lobe in patients with temporal lobe epilepsy before and after surgical resections. The study is expected to yield information on the organization of language in the temporal lobes and how unilateral temporal lobe lesions and lobectomy cause relocation of language mechanisms in the lesioned and in the other hemisphere. It will also be a preliminary step in the development of a clinically useful procedure for locating critical language areas in potential surgical candidates.
Upon successful completion of this study, the investigators expect the study's contribution to be the development of noninvasive imaging biomarkers to predict IEEG functional dynamics and epilepsy surgical outcomes. Findings from the present study may inform current and new therapies to map and alter seizure spread, and pave the way for less invasive, better- targeted, patient-specific interventions with improved surgical outcomes. This research is relevant to public health because over 20 million people worldwide suffer from focal drug-resistant epilepsy and are potential candidates for cure with epilepsy surgical interventions.
The general purpose of this observational study is to examine biomarkers associated with the pathology of neurodegenerative diseases to potentially develop novel therapeutic approaches.
Background: Epilepsy affects about 1 percent of the U.S. population. Most people with epilepsy respond well to medicine, but some do not. Researchers want people who have diagnosed or suspected epilepsy to participate in ongoing studies. They want to learn more about clinical care for epilepsy. They want fellows and residents to learn more about the care of people with epilepsy. Objectives: To learn more about seizures and find ways to best treat people with drug-resistant epilepsy. Eligibility: Adults and children ages 8 years and older with diagnosed or suspected epilepsy Design: Participants will be screened with: Physical exam Medical history Questionnaires Participants will have many visits. They may be admitted to the hospital for several weeks. Their medication might be stopped or changed. Participants will have many tests: Blood and urine tests EEG: Wires attached to the head with paste record brain waves. This may be videotaped. Thinking and memory tests MRI: Participants lie on a table that slides in and out of a tube. They perform simple tasks in the tube. MEG: Participants lie on a table and place their head in a helmet to record brain waves. PET scan: Participants lie on a table that slides into a machine. A small amount of radioactive dye is injected into their arm with an IV. For the IV, a small tube is inserted into the arm with a needle. Participants will stay enrolled in this study if they join other epilepsy-related studies. They may be contacted at intervals for follow-up. Their participation will end if they have not been seen clinically for their epilepsy for 3 years.
This is a prospective study investigating the utility of Brain Network Activation (BNA) analysis in patients with epilepsy.
Background: - The brain chemical serotonin helps nerve cells communicate. Previous research suggests that serotonin activity may be lower in brain areas where seizures start, and that increasing activity at the serotonin receptor site on nerve cells may help prevent seizures. Researchers are interested in determining whether the experimental medication PRX-00023, which increases the activity of serotonin receptors, can reduce seizure frequency in people whose seizures are not well-controlled on antiseizure medication. PRX-00023 has not previously been studied in people with epilepsy and has not previously been given to people taking antiseizure medication at the same time. Objectives: - To evaluate the effectiveness of PRX-00023 in reducing the frequency of epileptic seizures that start from only one part of the brain. Eligibility: - Individuals between 18 and 65 years of age who have frequent epileptic seizures even after trying at least two different standard anti-seizure medications (either at the same time or one after the other). Design: * The study requires 9 outpatient visits to the NIH Clinical Center over a 34-week period. Individuals who choose to participate in additional studies may be an inpatient during some of these visits. * Participants will be screened with a medical history and physical examination, blood and urine samples, ECG, EEG, neuropsychological studies, imaging studies, including PET and MRI scans * Participants will have a 6-week observation and evaluation period before starting the study medication. Participants who have at least four seizures during this period will be eligible for the treatment portion of the study. * All participants will receive either PRX-00023 or a placebo pill twice daily for 12 weeks, and will have regular clinic visits with blood samples and imaging studies. * After the 12-week period, participants will have a 2- to 3-week washout period without any study medication. * Participants will then have another study medication period, and will receive the opposite pill (PRX-00023 or placebo) from the one taken in the first treatment phase. Participants will continue to have regular clinic visits with blood samples, ECG, EEG and neuropsychologicalstudies. * One month after the end of the second study medication phase, participants will have a followup evaluation with a physical examination, blood tests, ECG, EEG, mood and neuropsychological tests. Outcome measures: The primary outcome measure for drug efficacy will be: Mean difference in seizure frequency comparing the active and placebo periods. Secondary outcome measures for efficacy will be: Proportion of patients with greater than or equal to 50% lower seizure rate on PRX-00023 than placebo Hamilton Depression and Anxiety Rating scales Performance on mood and neuropsychological testing scales
Background: - Drug resistant epilepsy is the term used to describe epilepsy that cannot be controlled by medication. Many people whose seizures do not respond to medication will respond to surgical treatment, relieving seizures completely or almost completely in one-half to two-thirds of patients who qualify for surgery. The tests and surgery performed as part of this treatment are not experimental, but researchers are interested in using the data collected as part of routine standard epilepsy care to better understand epilepsy and its treatment. Objectives: - To use surgery as a treatment for drug resistant epilepsy in children and adults. Eligibility: - Children and adults at least 8 years of age who have simple or complex partial seizures (seizures that come from one area of the brain) that have not responded to medication, and who are willing to have brain surgery to treat their medically intractable epilepsy. Design: * Participants will be screened with a medical history, physical examination, and neurological examination. Imaging studies, including magnetic resonance imaging and computer-assisted tomography (CT), may also be conducted as part of the screening. Participants who do not need surgery or whose epilepsy cannot be treated surgically will follow up with a primary care physician or neurologist and will not need to return to the National Institutes of Health for this study. * Prior to the surgery, participants will have the following procedures to provide information on the correct surgical approach. * Video electroencephalography monitoring to measure brain activity during normal activities within a 24-hour period. Three to four 15-minute breaks are allowed within this period. * Electrodes placed directly in the brain or on the surface of the brain to measure brain activities and determine the part of the brain that is responsible for the seizures (seizure focus). * Participants will have a surgical procedure at the site of their seizure focus. Brain lesions, abnormal blood vessels, tumors, infections, or other areas of brain abnormality will be either removed or treated in a way that will stop or help prevent the spread of seizures without affecting irreplaceable brain functions, such as the ability to speak, understand, move, feel, or see. * Participants will return for outpatient visits and brain imaging studies 2 months, 1 year, and 2 years after surgery.