Clinical Research Directory

Noninvasive Pre-surgical Evaluation of Patients With Focal Epilepsy and Establishment of a Normative Imaging Database

Objectives: The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions. Study population: 300 adults and children (age 8 and older) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers. Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits. Outcome measures: The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions.

Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy

Background: \- The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a neurological disease that causes seizures. It can affect this barrier. Researchers think a contrast agent called mangafodipir might be better able to show areas of the brain that epilepsy affects. Objective: \- To see if mangafodipir is well tolerated and safe. To see if magnetic resonance imaging (MRI) using either mangafodipir or gadolinium can show areas of blood-brain barrier breakdown in people with epilepsy. Eligibility: * People ages 18-60 who: * Have epilepsy not controlled by drugs * Prior or concurrent enrollment in 18-N-0066 is required Design: * Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Participants will have up to 6 visits in 1-3 months. One visit is an inpatient stay lasting 2-10 days. Visits may include: * Video-EEG monitoring for participants with epilepsy * An IV catheter put in place: a needle guides a thin plastic tube into an arm vein. * Getting mangafodipir through the IV. * Getting gadolinium through the IV. * Up to 6 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides into a metal cylinder. They are in the cylinder for 45-90 minutes, lying still for up to 10 minutes at a time. The scanner makes loud knocking sounds. Participants will get earplugs. * A final MRI at least 2 weeks after receiving mangafodipir.

BHV-7000 Responsive Neurostimulation System (RNS) Study

This is an open label study to assess the biological effect of BHV-7000 on abnormal activity recorded by the RNS System in patients with focal epilepsy implanted with the RNS System. BHV-7000 is a potassium channel activator being evaluated for use in epilepsy. Participants are offered the drug for 4 weeks. Activity during that treatment period is compared to a 90-day retrospective baseline period in which other medications and device settings were stable, and also to a 4-week withdrawal period after treatment is discontinued. The study is open to patients with RNS regardless of whether they report clinical seizures, as long as the device recordings continue to show epileptiform activity.

Healthy Aging in People With Epilepsy Program

The goal of this clinical trial is to develop and test an educational program about dementia in older adults living with epilepsy. The main questions it aims to answer are: 1. Can providing education on healthy aging, chronic disease management, dementia, and modifiable lifestyle dementia risk factors improve dementia knowledge and health literacy among older adults with epilepsy? 2. Can aging related education and resources improve quality of life among older adults with epilepsy? Participants will: * Be randomized to an intervention group or a control group. * Complete a 12-week group educational program (intervention group). * Complete pre- and post-program evaluation (intervention and control groups).

Effect of Rose Odor Exposure on Ictal Apnea

This study will investigate the potential benefits of rose scent in reducing the risk of Sudden Unexpected Death in Epilepsy (SUDEP) in patients with epilepsy. Participants will engage in their routine inpatient observational EEG monitoring for 24 hours followed by an additional 24 hours of observational EEG monitoring with continuous exposure to rose scent, during which an essential oil diffusor with rose scent will be placed in their hospital room. During these 48 total hours of the study, participants will wear a respiratory monitoring belt across their upper chest to measure their breathing. Potential risks include distress or discomfort when smelling the rose scent used in the study, a physical reaction to the rose scent, and discomfort or feelings of restrictiveness when wearing the respiratory monitoring belt. The total time commitment of the study is 48 consecutive hours over the course of the participants' inpatient EMU stay, during which there will be no restrictions on daily activities during the standard inpatient EMU admission except that participants must wear their respiratory belt for a majority of this 2-day period.

Spatial Memory and Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) can cause memory disorders, including long-term forgetfulness due to a failure to consolidate verbal but also spatial information. The forgetting phenomenon presented by these epileptic patients is called accelerated forgetting in the literature and remains difficult to objectify during cognitive assessments. It is indeed particularly complicated to evaluate long-term spatial memory and to account for the topographical complaint, although recurrent, of patients with this TLE. A navigation task being proposed as part of the neuropsychological assessment of patients with a spatial memory complaint, it is interesting to study the performance pattern of patients with TLE by comparing them to a group of control subjects matched in age and gender in order to verify whether there is significant long-term forgetting and whether there is a significant difference between Right TLE and Left TLE. Indeed, several studies have demonstrated this accelerated long-term forgetting in epileptic patients (Cassel et al., 2016; Lemesle et al., 2017; Landry et al., 2022; Blake et al., 2020) but few with a retention delay of several weeks (Tramoni et al., 2009). This study allows us to statistically analyze the effects of these two groups: epileptic patients and healthy volunteers, but also to combine the effect of the laterality of epilepsy specifically on spatial memory performance.

Subcortical Arousal in Perceptual Awareness

The study consists of prospective enrollment of healthy participants and patients with epilepsy, as well as analysis of an existing data set. Healthy participants will be studied with fMRI, eye metrics and behavioral testing at Yale. Patients will be studied with intracranial thalamic and cortical recording and stimulation, eye metrics and behavioral testing.

Clinic-based and Technology-Supported Sleep Intervention for Pediatric Epilepsy

Sleep problems are more common and more severe in children with epilepsy. The purpose of this study is to develop and evaluate the effect of a clinic-based and technology-supported sleep intervention for improving sleep and health in children with epilepsy and their parents.

Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures

This is a clinical research study for an investigational drug called RAP-219 in adult participants with focal seizures. This study is being conducted to determine if RAP-219 is safe and effective in reducing focal seizure frequency.

RNS System NAUTILUS Study

To demonstrate that the RNS System for thalamic stimulation is safe and effective as an adjunctive therapy for the reduction of primary generalized seizures in individuals 12 years of age or older who have drug-resistant idiopathic generalized epilepsy.

Surgery as a Treatment for Medically Intractable Epilepsy

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.

Diagnosing Epilepsy To EffeCT Change

The purpose of this research is to address the challenges of diagnosing and long-term management of epilepsy in participants whose seizures are not well captured by standard electroencephalography (EEG) tests and who cannot use or are not able to use more standard monitoring techniques. This research will compare the Minder System to standard of care in providing reliable seizure data. The Minder System was granted De Novo classification by the U.S. Food and Drug Administration (FDA) and is not investigational. Participants will consent to join the study and be implanted with the Minder device; or consent to join the study and continue with their Standard of Care (SOC) as a control group. Participants chose to be implanted with the Minder device will have the device implanted under their scalp. After implantation, participants will be randomly assigned to a group where their treating physician will have access to the EEG data collected by the Minder System or a group where their treating physician does not have access to the EEG data collected by the Minder System. Participants receiving the Minder System will not know which group they are in (blinded) until the study ends. All participants will continue to be followed by their treating physician and undergo assessments and visits until enough information is available to determine a treatment plan or the 6-month follow-up visit.

Study of the Pharmacokinetics, Safety, and Tolerability of ZONISADE in Children 1 Month to 17 Years of Age With Partial-onset Seizures

The purpose of this research is to determine the optimal dose, safety and tolerability of zonisamide oral suspension in children ages 1 month to 17 years of age who have partial-onset (focal) seizures. The study consists of four periods: a Screening Period (about 14 days), a Titration Period (8 weeks), a Maintenance Period (4 weeks), and a Follow-Up Period (1 week).

Investigating Epilepsy: Screening and Evaluation

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.

Electrical Impedance Tomography of Epilepsy

The purpose of this study is to determine if Electrical Impedance Tomography (EIT) can produce reproducible and accurate images in people with epilepsy compared to existing standards such as MRI, CT or EEG. Electrical Impedance Tomography is a relatively new medical imaging method, which has the potential to provide novel images of brain function. It is fast, portable, safe and inexpensive, but currently has a relatively poor spatial resolution. It produces images of the internal electrical impedance of a subject with epilepsy using rings of ECG like electrodes on the skin, intracranial electrode mats or deep electrodes implemented surgically as part of clinical assessment. EIT recording will take place in parallel with the routine recording on the ward. Following completion of the recording, the EIT images will subsequently be analysed and compared to other imaging data for accuracy.

Brain Metabolism Observed at 3 Tesla or 7 Tesla in Health and Metabolic Disease

The goal is to develop methodology to monitor flux in the citric acid cycle in brain via 13C nuclear magnetic resonance (NMR) spectroscopy at 7 Tesla or 3 Tesla.

Study of Direct Brain Recording and Stimulation for Memory Enhancement

Background: \- Epilepsy is a seizure disorder. Sometimes it is treated with surgery. During surgery, electrodes are placed on or in the brain. Researchers want to learn more about memory and the brain. They want to do tests on people who are having epilepsy surgery. Objective: \- To learn more about memory and brain function by recording brain cell activity during memory tasks. Eligibility: \- Adults age 18 - 65 who have medically intractable epilepsy and will have electrodes placed to identify the source of their seizures. They must be currently enrolled in protocol 11-N-0051. Design: * Participants may do memory tests before the electrodes are put in, while they are in place, and after surgery. Researchers may stimulate areas of the brain with small pulses of electricity. * Researchers will start recording brain activity at least 12 hours after electrodes are placed. They will record while participants are awake and asleep. They will record before, during, and after seizures. * Participants may have up to 3 testing sessions daily over the 1-3 weeks the electrodes are in place. Each session will last 20-60 minutes. * Participants will play games on a laptop. Sometimes they may use a button or joystick. This can be done in bed in the hospital. * Participants may be given a list of words and asked to recall them in a short time. * Participants may be given pairs of items and asked to remember how they are related. * Participants may be asked to learn their way around a virtual town on the computer. Their eye movements may be tracked by a small camera.

Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1

This is a clinical research study for an investigational drug called RAP-219 in adult participants with focal seizures. This study is being conducted to determine if RAP-219 is safe and effective in reducing focal seizure frequency.

Lily's Grace Temporal Interference

This study is to evaluate the effectiveness of targeted Transcranial Electrical Stimulation with Temporal Interference (TES-TI) interventions to boost Non-Rapid Eye Movement (NREM) sleep, decrease seizures and promote emotional health in patients with epilepsy. Up to 24 participants (8 control participants for technical optimization prior to recruitment and 16 patients with epilepsy) will be enrolled and can expect to be on study for up to 24 months.

AI-Based Mobile Intervention on Medication Non-Adherence and Transition

This study aims to examine whether the AI-personalized version of the Medilepsy® app is more effective than the non-AI (standard version without AI personalization) can improve key outcomes, such as medical adherence and transition readiness, among underserved adolescents and young adults with epilepsy, ages 14-24, in Florida, USA. Outcomes are organized into primary (effectiveness), secondary (usability), and exploratory (language experience) endpoints.

NYU Epilepsy Self-Management Study

The investigators will conduct two-arm randomized controlled trials (RCTs) comparing effects of UPLIFT vs. enhanced usual care and PACES vs. enhanced usual care, respectively, on quality of life, depressive symptoms and seizures over 12 months in NYU patients with epilepsy.

Tumor Related Epilepsy

Background: Some people with brain tumors have seizures related to the tumor. This is called tumor-related epilepsy. Usually brain tumors are treated by removing as much of the brain tumor as possible without causing problems. Researchers think this may improve the outcome for people with brain tumors. It may completely relieve or greatly reduce the number of seizures they have. Objectives: To evaluate people with brain tumors that are associated with seizures and to offer surgical treatment. Also, to study how surgery affects seizures. Eligibility: People age 8 and older who have a brain tumor with associated seizures. They must be willing to have brain surgery to treat their epilepsy. Design: Participants will be screened with a review of their medical records. Participants will have a medical history and physical exam. Participants will be admitted to the hospital at NIH. They will have Medical history Physical exam Neurological exam Tests of memory, attention, and thinking Questions about their symptoms and quality of life Blood drawn They may also have: MRI or CT scan. They will lie on a table that slides in and out of a machine that takes pictures. For part of the MRI, they will get a dye through an intravenous (IV) catheter. Video electroencephalography monitoring. Electrodes will be placed on the scalp. The participant s brain waves will be recorded while doing normal activities. Participants will be videotaped. Participants will keep a seizure diary before and after surgery. Participants will have surgery to remove their brain tumor and the brain area where their seizures start. They will stay in the hospital up to a week after surgery. Participants have for follow-up visits at NIH.

Genetic Diagnosis in Inborn Errors of Metabolism

Inborn Errors of metabolism comprise a large number of rare conditions with a collective incidence of around 1/2000 newborns. Many disorders are treatable provided that a correct diagnosis can be established in time, and for many diseases novel therapies are being developed. Without treatment, many of the conditions result in early death or severe irreversible handicaps. The Centre for Inherited Metabolic Diseases, CMMS at Karolinska university hospital, is an integrated expert center where clinical specialists work closely together with experts in laboratory medicine, combining clinical genetics, clinical chemistry, pediatrics, neurology, and endocrinology. The center serves the whole Swedish population with diagnostics and expert advice on IEM and has a broad arsenal of biochemical investigations designed to detect defects in intermediary metabolism.

Electrical Impedance Tomography & Selective Stimulation of Vagus Nerve

Electroceuticals is a new field in which the goal is to treat a wide variety of medical diseases with electrical stimulation of autonomic nerves. A prime target for intervention is the cervical vagus nerve as it is easily surgically accessible and supplies many organs in the neck, thorax and abdomen. It would be desirable to stimulate selectively in order to avoid the off-target effects that currently occur. This has not been tried in the past, both because of limitations in available technology but also because, surprisingly, the fascicular organisation of the cervical vagus nerve is almost completely unknown. The aim of this research is to investigate the functional anatomy of fascicles in the cervical vagus nerve of humans. This will include defining innervation to the heart, lungs and recurrent laryngeal and, if possible, the oesophagus, stomach, pancreas, liver and gastrointestinal tract. It will be achieved by defining fascicle somatotopic functional anatomy with spatially-selective vagus nerve stimulation (sVNS) and the new method of fast neural imaging with Electrical Impedance Tomography (EIT). EIT is a novel imaging method in which reconstructed tomographic images of resistance changes related to the opening of ion channels over milliseconds can be produced using rings or arrays of external electrodes. In humans, using a nonpenetrating nerve cuff with sVNS or fast neural EIT, this will be performed for 30 minutes transiently during an operation to insert a vagal nerve stimulator for treatment of epilepsy and deliver images in response to activity such as respiration or the electrocardiogram (ECG).