Clinical Research Directory

Cholinergic Enhancement of Theta

The goal of this study is to learn about the effects of Cobenfy KarXT (xanomeline and trospium chloride) on episodic memory processing, including specific effects on areas of the brain involved in memory and changes it may have on brain activity. The investigators will do this by testing epileptic patients who are already undergoing intracranial surgery for seizure monitoring, and measuring the activity from the brain areas being assessed. The main questions it aims to answer are 1) whether Cobenfy KarXT changes memory activity based on its agonist effect on muscarinic receptors and acetylcholine, and 2) what the nature of these brain activity changes are. This work builds on previous experiments evaluating cholinergic antagonists. Participants will complete two treatment arms. One of these will be with the drug, and the other will be with a placebo pill, so that the participants are unaware which session the actual drug has been received. Patients will complete a verbal serial recall and/or associative recognition task each of the two days. An anesthesiologist or patient nurse will administer either the drug or the placebo at a critical point which addresses both of the research questions. Researchers will compare the brain activity between the two treatment arms to determine what brain activity changes, and whether there is an additional behavioral effect on memory.

A Pilot Study to Evaluate the Efficacy and Safety of NaviFUS™ System Neuromodulating Treatment for Patients With Drug Resistant Epilepsy

This will be a prospective, pilot, open-label, two-arm, parallel-group, randomized study to evaluate the efficacy and safety of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant epilepsy (DRE).

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.

TIS for Drug Resistant TLE

Temporal interference (TI) stimulation is a new neuromodulation method. Compared with traditional neuromodulation therapy, TI has deep targeting and focusing, and it has been confirmed to modulate sleep, cognition, and movement disorders. Recent study shown that TI stimulation targeting the hippocampus could significantly reduce epileptiform discharges, but its efficacy on seizures was still unclear. Therefore, the aim of this study is to observe the therapeutic effect of TI stimulation targeting the hippocampus in patients with refractory temporal lobe epilepsy (TLE) for 5 days, and to provide support for clinical trials of non-invasive treatment of refractory TLE.

A Safety, Tolerability, and Preliminary Efficacy of Low-intensity Focused Ultrasound Neuromodulation in Patients With Drug-resistant Epilepsy

This will be a prospective, open-label, single-arm, multi-center, pilot study to evaluate the safety, tolerability, and preliminary efficacy of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant unilateral or bilateral temporal lobe epilepsy (DR-TLE).

MiCrobiota-gut-brain Axis in Resistant Epilepsy

Epilepsy is one of the most common neurological chronic conditions with a serious burden on patients, their caregivers, and society. Drug-resistant epilepsy (DRE) heightens this burden. New approaches are thus a priority. Studies in animal models and humans have shown the link between gut microbiota (GM) and the central nervous system in health, neurological conditions, and neurodevelopmental disorders. DRE has been linked to GM dysbiosis. Preliminary findings in children with DRE showed GM modifications when responding to a ketogenic diet. The mediator role of GM has not yet been studied in DRE patients undergoing surgery/vagal nerve stimulation. CARE's central hypothesis is that the GM and its metabolic profile could contribute to clinical outcomes following these different therapeutic procedures. Identifying microbial biomarkers will enable us to deepen the knowledge of the role of gut-brain axis in epilepsy and to tailor the intervention to each patient based on GM modulation.

Intracranial Stimulation Mapping In Epilepsy

This is a single group prospective study to determine the feasibility for generating brain maps that localize cerebral functions and inter-regional information flow in partial epilepsy in adult patients.

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.

An Examination of Whether Infrared Light Therapy Can Reduce Stress in People With Epilepsy

Do you have Epilepsy? Would you like to participate in a study using PhotoBioModulation (PBM)? PBM is being researched for potential benefits in resolving many stress-related brain disorders. It is a non-invasive technique that delivers light energy to cells and tissues that can promote brain stabilization and self-regulation, cell repair, reduce oxidative stress, and enhance cellular function. We ask you to participate for about 3-4 months and come to our facility for 30 minute sessions 3x a week for 15 weeks. You will receive extensive metabolic testing and an Õura ring for your participation.

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.

Diagnosing Epilepsy To EffeCT Change Long-Term Follow-Up

The purpose of this research is to address the challenges of correctly monitoring, managing, and diagnosing 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 is being done to understand how the Minder System helps physicians make decisions about participant's epilepsy treatment after an actionable event. The Minder System was granted De Novo classification by the U.S. Food and Drug Administration (FDA) and is not investigational. Participants that have completed the DETECT study and received the Minder System previously will consent to join this long-term follow-up observational study. The study will collect information about general wellbeing, use of healthcare services, and experience using the Minder data over time to support long-term epilepsy care. All participants will continue to be followed by their treating physician and undergo assessments and visits every six (6) months until two (2) years after receiving the Minder device.

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. ...

The Safety and Efficacy Evaluation of Everolimus as an Adjunctive Treatment for Focal Refractory Epilepsy

The aim of this study is to evaluate the clinical efficacy of everolimus as an adjunctive therapy for refractory epilepsy. The significance lies in addressing whether the mTOR inhibitor sirolimus has antiepileptic adjunctive effects for a broader range of patients with refractory epilepsy, with the hope of providing a new mTOR-targeted antiepileptic adjunctive medication regimen that is administered only during epileptic events and can be widely used for various types of refractory epilepsy.

Behavioral and Neuronal Correlates of Human Mood States

Optimizing treatments in mental health requires an easy to obtain, continuous, and objective measure of internal mood. Unfortunately, current standard-of-care clinical scales are sparsely sampled, subject to recency bias, underutilized, and are not validated for acute mood monitoring. The recent shift to remote care also requires novel methods to measure internal mood. Recent advances in computer vision have allowed the accurate quantification of observable speech patterns and facial representations. The continuous and objective nature of these audio-facial behavioral outputs also enable the study of their neural correlates. Here, the investigators hypothesize that video-derived audio-facial behaviors have discrete neural representations in the limbic network and can provide a critical set of reliable longitudinal estimates of mood at low cost across home and clinic settings.

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.

Bridging the Gap: Educating Patients on Social Determinants of Health to Improve Epilepsy Surgery Access and Outcomes

The goal of this study is to identify the needs and barriers to accessing and undergoing epilepsy surgery for patients with epilepsy and then to pilot an educational program regarding the social determinants of health and how they can influence surgical rates and epilepsy outcomes. For the first part, patients (age 18+) and providers will be asked to complete surveys and participate in focus groups to identify gaps and barriers that limit access to and use of epilepsy surgery. For piloting the education program, patients (age 18+) at the Cleveland Clinic Epilepsy Monitoring Unit will be randomized to intervention or control. Those in the intervention group, in addition to their usual care, will also receive educational materials on social determinants of health and their influence on surgical rates and epilepsy outcomes. Those in the control group will receive their usual care. Both groups will be asked to fill out surveys and questionnaires at the beginning of their stay, at the end of their stay, and if they elect to have surgery, 12 months after surgery.

Microelectrode Recordings From the Vagus Nerve in Awake Humans

This Anchillary project uses a refined technique of ultrasound-guided microneurography of the human cervical vagus nerve, an approach developed by Professor Vaughan Macefield and used safely to-date in 44 prior study participants. The overall goal of this project is to build upon prior data obtained using this approach by undertaking a detailed neurophysiological investigation of the human vagus nerve and to identify the nerve fibers activated during vagal nerve stimulation (VNS) in participants with implanted VNS devices in response to different stimulation parameters. In addition to providing data in unprecedented detail into the physiology of the human vagus nerve, this project will investigate different stimulus intensities, durations and frequencies that differentially excite myelinated and unmyelinated nerve fibers. These results will inform the CSP and guide future development of novel neural interfaces for VNS for various clinical applications.

RESEARCH EVALUATING VAGAL EXCITATION AND ANATOMICAL LINKS

The acute and chronic effects of VNS stimulation on various on the autonomic nervous, cardiovascular, immune, and metabolic systems will be compared from noninvasive and minimally invasive physiological recordings and blood draws at various time points throughout the study. These interventions and assessments will be performed in individuals 18 years of age and older who are implanted with a VNS device, which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. The REVEAL study is not a treatment study; its primary objective is to scientifically investigate the contributing roles of efferent versus afferent vagus nerve modulation of multiple peripheral organs and their dependence on stimulation parameters, in which participants are those who have been implanted with a VNS device be receive standard of care treatment for their epilepsy or depressive disorder.

The Benefits of a Care Pathway Combining Remote Monitoring and Support From a Nurse After a Change in Anti-epileptic Treatment: a Pilot Study

Epilepsy is a chronic condition affecting approximately 600,000 people in France. Epilepsy treatment relies on antiepileptic drugs, the effectiveness of which depends on adherence to medication schedule, with missed doses increasing the risk of seizures. As with any chronic illness, epilepsy presents a significant challenge in terms of treatment adherence. Furthermore, despite good medication adherence, 30% of patients remain drug-resistant. Therefore, the aim is to create a remote monitoring program, supported by a nurse, lasting six months after the introduction of a new antiepileptic drug, to support the patient until their next appointment with a neurologist. This system would optimize and secure the care pathway during treatment changes by improving the detection of side effects and/or a resurgence of seizures requiring medication adjustments.

Subcortical Arousal in Perceptual Awareness

The study is a multi-site study and will be conducted at up to 11 investigative sites in the United States. The study will investigate subcortical arousal circuits in visual perception using techniques with complementary strengths based on promising initial studies.

Study for the Diagnosis and Treatment of Drug-resistant Focal Epilepsies

Epilepsy is a clinical condition that affects about fifty million people worldwide, with an estimated occurrence of 16-51 new cases per 100,000 people each year. In 60% of these patients, the origin of seizures is due to a localized (focal) alteration of the brain. In about 25 percent of patients with focal epilepsy, drug treatment is ineffective, a condition defined by the International League Against Epilepsy (ILAE) as drug-resistant epilepsy ; this condition results in a drastic reduction in quality of life associated with psychosocial dysfunction and an increased risk of sudden death. A possible treatment alternative for drug-resistant patients is ablation of the epileptogenic zone through surgical methods that are effective and safe when patients are carefully selected. The percentage of patients with epilepsy who are completely cured after surgery is about 70% for temporal lobe epilepsies, and can be as high as 90% in the case of some brain malformations. Pre-surgical screening and therapeutic intervention (particularly surgery) have health care costs that are amortized over 2-6 years depending on the procedures required before surgery. In the last decade, moreover, the refinement of noninvasive/mini-invasive methods such as radiosurgery, Magnetic Resonance-guided Focused Ultrasound (MRgFUS) and laser interstitial thermal therapy (LiTT) have allowed us to hypothesize a possible specific treatment of drug-resistant patients with epileptogenic areas that are difficult to reach with traditional surgery and patients with complex comorbidities for whom the risks of standard resective surgery would outweigh the possible benefits. Finally, there is a subgroup of patients with drug-resistant epilepsy who cannot undergo ablative surgery. In these patients, seizures originate from multiple areas of the brain (multifocal epilepsy) or the epileptogenic area affects functionally eloquent areas. In these cases, alternative functional treatments are proposed, which aim to decrease the frequency and intensity of seizures and the need for medication, such as: i) application of a vagal stimulator, a pulse generator that is implanted in the chest and connected to the vagus nerve, ii) implantation of deep brain stimulation devices, iii) neuromodulation. Therefore, careful selection of patients during the diagnostic/pre-surgical process is crucial. The multimodal assessments under study, proposed in support of clinical practice, aim to improve such selection by analyzing the causative factors of seizures, the location of the epileptogenic zone, and the clinical-epileptological course of patients who are candidates for surgical or functional treatment of epilepsies.

Remote Neuropsychological Assessment of Patients With Neurological Disorders and Injuries

For the last decades, many aspects of human life have been altered by digital technology. For health care, this have opened a possibility for patients who have difficulties travelling a long distance to a hospital to meet with their health care providers over different digital platforms. With an increased digital literacy, and an aging population often living in the countryside, far from hospitals or other health care settings, an increasing need for digitalization of meetings between patients and health care personnel is inevitable. However, neuropsychological assessment is one sort of health care not possible to directly transfer into digital form. These evaluations are most often performed with well validated tests, only to be used in a paper-pencil form with a specially trained psychologist during physical meetings. The aim of this project is to investigate whether a newly developed digital neuropsychological test battery can be used to perform remote assessments of cognitive function in patients with neurological injuries and impairments. To this date, there are no such test batteries available in the Swedish language. Mindmore (www.mindmore.com) is a test system developed in Sweden, performing neuropsychological tests on a tablet, but still with the psychologist present in the room. This system is now evolving into offering the possibility for the patient to perform the test in their own home, using their own computer or tablet. The aim of the present research project is to validate this latter system (Mindmore Distance), using the following research questions: 1. Are the tests in Mindmore Distance equivalent to traditional neuropsychological tests in patients with traumatic brain injury, stroke, multiple sclerosis, Parkinson's Disease, epilepsy, and brain tumor? 2. Can the results from Mindmore Distance be transferred into neuropsychological profiles that can be used in diagnostics for specific patient groups? 3. How do the patients experience undergoing a neuropsychological evaluation on their own compared to traditional neuropsychological assessment in a physical meeting with a psychologist?

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 it can show, on an MRI, areas of the brain that epilepsy affects. 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. Those with epilepsy will have 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. * 5 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. Gadolinium is given through an IV catheter.

Korus: a Device to Prevent Sudden Unexpected Death in Epilepsy (SUDEP)

The goal of this feasibility study is to test the Korus smart mattress in healthy volunteers. The main questions it aims to answer are: * Can Korus accurately detect body position in bed (left, right, supine, prone) * Can Korus reposition the subject from a prone to recovery (sideways) position? Participants will be asked to lie down on Korus and turn into various positions; when the prone position is detected, they will be repositioned.