Epilepsy

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 mg/kg/day during the first two weeks. The dose increases to 4 mg/kg/day in weeks 3-4 and to 6 mg/kg/day in weeks 5-6. After six weeks, the dose is adjusted weekly by 1 mg/kg/day based on the patient's condition, maintaining a dose between 4 and 6 mg/kg/day 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 evaluating ETX101, an investigational gene therapy delivered via AAV9, in infants and children with Dravet syndrome caused by SCN1A gene mutations. This study, called ENDEAVOR, includes participants from 6 months up to less than 18 years old and aims to assess the safety and effects of ETX101 on seizure frequency and developmental outcomes. The trial includes multiple parts with different age groups and study designs to understand its impact comprehensively. The study has three parts: Part 1A is an open-label dose-escalation phase for children aged 6 to less than 36 months, testing up to four dose levels of ETX101. Part 1B is an open-label phase for participants aged 48 months to less than 18 years, evaluating a single dose level. Part 2 is a randomized, double-blind, sham delayed-treatment control study for children aged 6 to less than 48 months, where participants are assigned in a 2:1 ratio to receive ETX101 or a sham procedure with delayed treatment. During participation, children will be monitored for changes in seizure frequency from before dosing to 52 weeks after treatment. Researchers will also assess cognitive and adaptive behavior development using standard scales like Bayley-4 and Vineland-3. Safety and efficacy will be closely observed through clinical evaluations, with follow-up lasting up to a year post-dosing to measure treatment outcomes and monitor health.

Researchers are conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore its possible links with various underlying diseases. This non-interventional, multicenter study aims to provide a pilot map of genetic variation in HLA that may be useful in medical research and clinical applications related to selected diseases. The study plans to include 12,000 participants over a total duration of 36 months. Each participant will attend one visit at a participating site during which they will provide demographic data, lifestyle information such as smoking and alcohol use, blood pressure measurements, details on diagnosed diseases and treatments, and recent laboratory test results if available. Buccal swab samples will be collected from each participant to extract DNA for HLA genotyping analysis. Selected samples will undergo further whole genome sequencing to investigate associations with autoimmune diseases. Participants will receive a personalized ancestry report after analysis completion. During the study visit, data collection includes demographic and health information, as well as laboratory and clinical test results from the past year. The genetic material from buccal swabs will be stored and processed for genetic analysis. Researchers will measure allele frequency of HLA alleles in the Greek population and assess the prevalence and risk associations of selected HLA-related diseases. The study's total duration is 36 months with results available at the end of this period.

Researchers are investigating the safety and effectiveness of elsunersen in children with early onset SCN2A Developmental and Epileptic Encephalopathy (DEE), a rare neurological condition characterized by frequent seizures starting before three months of age. This phase 3 clinical trial focuses on pediatric participants who have a specific genetic mutation called Gain of Function SCN2A variant confirmed by genetic testing. The study aims to see how elsunersen affects seizure frequency and other related measures over 24 weeks. Participants will receive open-label treatment with elsunersen administered intrathecally every four weeks for 24 weeks. Two dosing options are studied: 1 mg and 0.5 mg of elsunersen. The trial has multiple cohorts, each receiving the open-label treatment during the experimental period. There is no placebo group, and all participants will be monitored closely throughout the study. During the trial, participants will be evaluated on seizure frequency, clinical global impression scales, sleep assessments, and other efficacy measures at various time points over 24 weeks. Safety and tolerability of elsunersen will also be assessed throughout this period. The total participation duration covers the 24-week treatment and observation period, with ongoing evaluations to understand the drug's effects in this pediatric population.

Researchers are studying PRAX-222 in children aged 2 to 18 years who have early onset SCN2A developmental and epileptic encephalopathy (DEE), a rare form of epilepsy that begins before 3 months of age. This trial aims to learn about the safety and effects of multiple doses of PRAX-222 in this pediatric population. The study is sponsored by Praxis Precision Medicines and includes phases to assess safety and efficacy. Participants will receive different doses of PRAX-222 or a placebo in a randomized, double-blind design. The study includes an initial dose escalation phase with ascending doses, optional further dose escalations, fixed-dose treatment phases, and open-label treatment periods where all participants may receive PRAX-222. Placebo procedures are included to compare responses. The dosing schedule varies across these treatment phases. Throughout the trial, children will be monitored for treatment-emergent adverse events and seizure frequency at various timepoints up to 92 weeks. Assessments include seizure counts, clinical global impression scores, developmental milestones, EEG measures, behavior scales, quality of life, and sleep evaluations. This comprehensive monitoring helps researchers understand the treatment's safety and impact. Participation may last up to nearly two years depending on study phases.

Researchers are evaluating the effects of zorevunersen, an investigational antisense oligonucleotide medicine, in children with Dravet syndrome, a rare epilepsy disorder caused by reduced Nav1.1 protein due to SCN1A gene mutations. This Phase 3, global, randomized, double-blind, sham-controlled study aims to assess the safety, tolerability, and potential to modify the disease by increasing Nav1.1 protein levels from the nonmutant gene copy. The study also measures changes in seizure frequency, behavior, cognition, clinical status, and quality of life. Participants are randomly assigned to one of two groups for Treatment Period 1, lasting about 52 weeks: either receive zorevunersen or undergo a sham procedure without drug administration. Zorevunersen is given by intrathecal injection at specific days and doses during this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen at defined intervals and doses. Patients may also join an open-label extension study if they meet criteria after the main study. Throughout the study, patients will be monitored regularly to assess seizure changes at weeks 28 and 52, as well as adaptive behavior using the Vineland-3 scale. Safety and tolerability are closely followed with standardized evaluations. The study lasts at least 84 weeks, including both treatment periods. Researchers aim to understand how zorevunersen may impact major motor seizures and overall functioning in children with Dravet syndrome.

Researchers are conducting a Phase Ib/II, first-in-human, multicenter, open-label study to assess the safety, tolerability, and how the body processes and responds to the drug S230815 in children aged 2 to 12 years with Developmental Epileptic Encephalopathy caused by a genetic variant in the KCNT1 gene. To join, participants must have a confirmed diagnosis through genetic testing. The study is sponsored by Institut de Recherches Internationales Servier and focuses on this rare pediatric epilepsy condition. The study includes a screening period followed by two parts. Part 1 tests multiple increasing doses of S230815 given as a solution for injection. Part 2 is a long-term treatment extension where participants continue receiving the same dose for up to 72 weeks after completing Part 1. Participants will move seamlessly from Part 1 to Part 2, staying in their assigned dose group. Participants will be closely monitored throughout, with assessments including daily seizure logs and periodic 24-hour video EEGs to record seizure frequency. Researchers will also evaluate drug levels in the cerebrospinal fluid and blood plasma. Safety is carefully tracked by recording any adverse events through the study, which can last up to 116 weeks. The study aims to understand how safe and tolerable S230815 is and how it affects seizures in this patient group.

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 studying adolescents and young adults with autism spectrum disorder (ASD), a condition marked by difficulties in communication, social skills, and repetitive behaviors. The study aims to understand how a brain stimulation technique called transcranial direct current stimulation (tDCS) might reduce symptoms like anxiety and impulsivity. The research also seeks to use brain activity data and clinical information to predict who will respond well to this treatment. Participants will receive active tDCS for 10 sessions over two weeks, one session per day on working days. During each 20-minute session, they will perform exercises designed to improve processing speed and executive function while receiving brain stimulation. After treatment, participants will be classified as responders or non-responders based on improvements in social responsiveness scores. Throughout the study, participants will undergo various assessments including behavioral scales, cognitive tests, and neurophysiological measurements at the start and after the treatment period. Researchers will track changes in social communication, repetitive behaviors, and brain function. This will help determine the effects of tDCS and identify characteristics that predict treatment response, with the total study duration extending up to the final follow-up in 2026.

Researchers are developing a multicenter registry to collect and share data on pediatric patients who have undergone deep brain stimulation (DBS) for movement disorders such as dystonia, epilepsy, Tourette syndrome, and mood disorders. The study aims to improve understanding of DBS safety and effectiveness in children, as current data are limited and individual centers often have too few cases for strong research. This registry will support large-scale analyses and help refine DBS as a treatment option for hyperkinetic movement disorders in the pediatric population. The study involves gathering both retrospective and prospective clinical data from multiple pediatric centers. The registry will collect information on surgical techniques, patient outcomes, implant sites, and long-term effects of DBS. This collaborative data-sharing approach enables comprehensive evaluation of which patients benefit most from DBS and how it impacts their quality of life over time. Participants include children aged 0 to 18 years who have already received or are scheduled to receive DBS for neurological movement disorders. Data will be collected over five years to monitor safety, efficacy, and quality of life outcomes. The study does not involve treatment administration but focuses on gathering and analyzing clinical information. Parental or legal guardian consent is required for prospective participation.