Seizure Disorder

Researchers are evaluating the effectiveness and safety of zonisamide as an additional treatment for children aged 1 to 14 years with focal epilepsy, including those with secondary generalized tonic-clonic seizures. The study aims to determine whether zonisamide can reduce the frequency of epileptic seizures and improve cognitive function, while also monitoring any treatment-related side effects. This open-label, observational study focuses on patients who have not achieved adequate seizure control with one antiepileptic drug. Participants will receive zonisamide tablets orally, starting at 2 mgkgday during the first two weeks. The dose increases to 4 mgkgday in weeks 3-4 and to 6 mgkgday in weeks 5-6. After six weeks, the dose is adjusted weekly by 1 mgkgday based on the patients condition, maintaining a dose between 4 and 6 mgkgday given once or twice daily. Children weighing 50 kg or more will receive adult-equivalent dosing. During the study, participants seizure frequency and cognitive function will be assessed at baseline, week 8, and week 20. Safety will be monitored through physical exams, vital signs, weight checks, and laboratory tests including liver and kidney function and blood counts. The study will use statistical software to analyze changes in seizure frequency and safety data. The total study duration is from August 1, 2024, to July 31, 2027.

Researchers are investigating ETX101, a gene therapy delivered via an adeno-associated viral vector, in infants and children diagnosed with SCN1A-positive Dravet syndrome. The study includes multiple age groups ranging from 6 months to under 18 years and aims to assess the safety and effects of ETX101. It is designed as a Phase 12, multicenter trial with different parts evaluating dose levels and treatment impact using a randomized, controlled approach in later stages. The study is divided into parts Part 1A uses an open-label, dose-escalation design to test up to four doses of ETX101 in participants aged 6 to under 36 months. Part 1B is open-label and tests a single dose in participants aged 48 months to under 18 years. Part 2 is a double-blind, randomized, sham delayed-treatment control study involving participants aged 6 to under 48 months, where participants receive either ETX101 or a sham procedure with delayed treatment. This part includes two cohorts and lasts up to 52 weeks. Participants will be closely monitored through the study with assessments of seizure frequency, cognitive and adaptive behavior changes using tools like the Bayley-4 and Vineland-3 scales, and clinical global impressions over 52 weeks. Safety and effectiveness are evaluated by comparing seizure counts before and after dosing. The study includes various cognitive and behavioral outcome measures and follows participants from dosing up to one year for treatment effects and safety observations.

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

This clinical trial evaluates the efficacy and safety of elsunersen in children with early-onset SCN2A Developmental and Epileptic Encephalopathy, a condition characterized by seizures beginning before 3 months of age. The study focuses on pediatric participants confirmed to have a gain of function SCN2A genetic variant, aiming to understand how elsunersen impacts seizure frequency and related symptoms. The trial is sponsored by Praxis Precision Medicines and is conducted at multiple centers. Participants receive intrathecal doses of elsunersen every 4 weeks for a total of 24 weeks. Two dosing levels, 1mg and 0.5mg, are being studied in an open-label design across three cohorts. All participants receive the study drug without a placebo comparison, and treatment effects on seizures and other clinical assessments are monitored throughout the treatment period. During the 24-week treatment, participants undergo regular evaluations to assess seizure frequency, clinical global impression of severity and improvement, and sleep quality among other outcomes. Safety and tolerability are also closely monitored. The trial includes baseline observation periods and follow-up assessments to track changes over time, providing a comprehensive view of elsunersens impact in this pediatric population.

Researchers are evaluating the maximum safe and tolerated dose of Levetiracetam LEV for treating neonatal seizures. This Phase IIb, open-label dose-escalation study aims to determine if higher doses of LEV than currently used can improve seizure control in newborns. The study includes infants at risk or confirmed to have neonatal seizures of mild to moderate severity, with continuous video EEG monitoring used to assess seizure activity and control. Participants initially receive a 60 mgkg dose of LEV. If seizures persist after this dose, they are randomized to either receive higher doses of LEV 90 mgkg, 120 mgkg, or 180 mgkg in increments or treatment with Phenobarbital PHB at 20-40 mgkg. Maintenance treatment with PHB may continue for five days either intravenously or orally if tolerated. The study includes three phases, with Phase 3 expanding to neonates with more severe seizure burden if earlier phases show efficacy. Throughout the study, participants are monitored with continuous EEG reviewed by neurophysiologists to assess seizure control over 24 hours and changes in seizure burden during the two hours after treatment. Safety, pharmacokinetics, seizure freedom rates, adverse events, and long-term outcomes up to eight years are evaluated. The study also assesses new technology for neonatal seizure detection. Participation may last several years due to extended follow-up for long-term outcomes.

Researchers are evaluating zorevunersen, an investigational antisense oligonucleotide drug, in children with Dravet syndrome, a rare and severe form of epilepsy. This Phase 3, global, multicenter, randomized, double-blind, sham-controlled study aims to assess the efficacy, safety, and tolerability of zorevunersen by measuring changes in major motor seizure frequency and other important aspects such as behavior, cognition, clinical status, and quality of life. Participants will be randomly assigned to receive either zorevunersen or a sham procedure during Treatment Period 1, which lasts about 52 weeks. Zorevunersen is given by intrathecal injection at specific doses and intervals throughout this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen for additional dosing over several months. Patients who complete the study may have the chance to join an open-label extension to continue receiving the drug. During the study, participants will undergo regular assessments including seizure monitoring, behavioral and cognitive evaluations, and health-related quality of life measurements. The primary outcome is the change in major motor seizure frequency at Week 28, with secondary outcomes assessed at Week 52. Safety and tolerability are also closely monitored. Overall participation lasts through both treatment periods and possible extension, with detailed follow-up to evaluate the drugs potential for disease modification.

Researchers are studying pediatric participants aged 2 to 12 years with Developmental Epileptic Encephalopathy caused by a genetic variant in the KCNT1 gene. This Phase IbII, first-in-human, multicenter, open-label study aims to assess the safety, tolerability, and how the investigational drug S230815 behaves in the body and affects the disease. The trial is sponsored by Institut de Recherches Internationales Servier and includes a screening period followed by two treatment parts. Participants will receive multiple ascending doses of S230815 administered intrathecally during Part 1 of the study. Those who complete Part 1 may continue into Part 2, a long-term treatment extension lasting up to 72 weeks, continuing with the same dose cohort as in Part 1. The treatment is given as a solution for injection, and dosing is designed to evaluate safety and drug effects over time. Throughout the study, participants will be closely monitored for adverse events and drug levels in cerebrospinal fluid and plasma. Seizure frequency will be tracked using daily logs and periodic 24-hour video EEG assessments. Researchers will also record the use of rescue medications. The total participation may last up to 116 weeks, including the screening, treatment, and follow-up visits, ensuring thorough evaluation of the drugs impact and safety profile.

Researchers are evaluating RAP-219, an investigational drug, for adults with refractory focal epilepsy, a condition involving difficult-to-control focal seizures. This open-label, multi-center study aims to assess the long-term safety, tolerability, how the drug behaves in the body, and its antiseizure activity in adults who have not responded well to previous treatments. Participants will receive RAP-219 starting with one 0.125 mg capsule daily for 3 days, then one 0.25 mg tablet daily for 28 days, followed by one 0.75 mg tablet daily for the rest of the treatment period. The study is open-label, meaning all participants know they are receiving RAP-219, and the treatment period may last up to 112 weeks with ongoing monitoring. During the study, participants will be regularly assessed for treatment-related side effects and seizure frequency compared to their baseline before treatment. Researchers will monitor seizure-free days, longest seizure-free intervals, and other seizure-related measures using clinical assessments and RNS system data. Safety will be tracked through adverse event reporting up to 8 weeks after the last dose. The total participation duration can be up to about 2 years, with ongoing evaluations throughout.

Researchers are investigating the use of transcranial direct current stimulation tDCS combined with cognitive training to address symptoms in adolescents with autism spectrum disorder ASD. ASD is characterized by challenges in communication, social skills, repetitive behaviors, and emotional distress triggered by environmental changes. This study aims to determine if baseline resting-state EEG and clinical data can predict which individuals respond to tDCS treatment, helping to improve intervention strategies. Participants will receive active tDCS over 10 sessions during two weeks, with one session per day on consecutive working days. Each session includes 20 minutes of tDCS combined with an online cognitive training program consisting of five exercises targeting information processing speed and executive function. After treatment, participants will be classified as responders or non-responders based on changes in social responsiveness scores. During the study, assessments will measure changes in social communication and repetitive behaviors using the Social Responsiveness Scale, cognitive function through various CANTAB tests, and neurophysiological measures at the start and immediately after the intervention. Researchers will monitor behavioral changes and executive function outcomes to evaluate the impact of the combined treatment over the study period ending in 2026.

Researchers are evaluating the feasibility of conducting a larger multi-site randomized controlled trial comparing two treatments for children and teenagers aged 11 to 18 who have functional seizures FS. This study focuses on testing how well recruitment, retention, acceptability, treatment adherence, and therapy fidelity work across three sites University of Alabama at Birmingham, Yale School of MedicineYale New Haven Childrens Hospital, and Baylor College of MedicineTexas Childrens Hospital. Participants will be randomly assigned to receive either Retraining and Control Therapy ReACT or Competent Adulthood Transition with Cognitive Behavioral, Humanistic, and Interpersonal Training CATCH-IT. Both treatments include 12 therapy sessions, with the first session held in person lasting about 2 hours and the following 11 sessions delivered via video telehealth lasting about 1 hour each. ReACT involves working with a therapist to develop a plan to manage seizures, while CATCH-IT uses online CBT modules for the parent and child, supported by 12 coaching sessions. Participants and their caregivers will complete baseline and follow-up visits via secure video calls, including questionnaires about mood, relationships, and seizure symptoms. They will keep a seizure diary throughout the study. Follow-ups occur one week and two months after therapy ends, with additional long-term follow-ups at six and twelve months. Researchers will measure recruitment success, acceptability, retention rates, treatment adherence, seizure frequency, quality of life, and other psychological and functional outcomes to guide future larger trials.