Thalamocortical Responsive Neurostimulation for the Treatment of Lennox-Gastaut Syndrome

丘脑皮质反应性神经刺激治疗 Lennox-Gastaut 综合征

基本信息

批准号：
10674542
负责人：
MARTHA J MORRELL
金额：
$ 295.93万
依托单位：
NEUROPACE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10674542
关键词：
12 year old Adverse effects Bilateral Biological Markers Blinded Brain Centromedian Thalamic Nucleus Childhood Clinical Clinical Research Clonic Seizure Computer Models Crossover Design Data Decision Support Systems Deep Brain Stimulation Detection Device Designs Devices Diffusion Magnetic Resonance Imaging Disease Electrodes Electroencephalography Electrophysiology (science)Elements Enrollment Epilepsy Etiology Evaluation FDA approved Feasibility Studies Follow-Up Studies Frequencies Functional disorder Future Gastaut syndrome Generalized Epilepsy Genetic Crossing Over Goals Impaired cognition Implant Injury Ipsilateral Lead Longterm Follow-up Machine Learning Magnetic Resonance Imaging Manuals Medial Medical Medical Imaging Mental Depression Modeling Neurons Online Systems Operative Surgical Procedures Outcome Parkinson Disease Pathway interactions Patients Pharmaceutical Preparations Physicians Pilot Projects Policies Population Post-Traumatic Stress Disorders Prefrontal Cortex Randomized Research Safety Seizures Selection for Treatments Single-Blind Study System Testing Thalamic structure Time Tonic Seizures Update Visualization addiction atonic seizure biomarker discovery biophysical model blind clinical efficacy clinical practice cohort computational network modeling design diaries early experience effective therapy improved interactive therapy lead optimization machine learning method mortality neuroimaging neurophysiology neuroregulation novel open label potential biomarker predict clinical outcome prototype recruit response safety testing tool

项目摘要

Project Summary / Abstract Lennox-Gastaut Syndrome (LGS) is a devastating form of childhood onset epilepsy with cognitive dysfunction and very frequent generalized onset seizures (GOS) often leading to injury. Driven by the lack of effective therapies and the demonstrated safety and efficacy of brain-responsive stimulation for medically intractable focal onset seizures (FOS), this study will test whether brain-responsive neurostimulation of thalamocortical networks (RNS-TCN) is a feasible strategy to treat LGS. Specifically, the project aims to: (1) acquire preliminary evidence for safety and efficacy in treating GOS of LGS with RNS-TCN; (2) create an interactive therapy-decision support system based on patient-specific computational network models and machine learning to identify optimal lead placement and stimulation parameters. Using the RNS® System, which is FDA approved for FOS, an early feasibility IDE study will be conducted at 6 epilepsy centers in 20 patients with LGS and medically intractable GOS. The patients will be enrolled in two cohorts of 10, with safety and efficacy milestones in the first cohort governing the enrollment of the second cohort. Patients will have two depth leads placed bilaterally in the centromedian nucleus of the thalamus and two subdural strip leads placed bilaterally on the medial prefrontal cortex. These targets are selected because they are implicated in the onset and spread of GOS in LGS. Leads will be located within each target such that stimulation maximally engages the thalamocortical network, guided by finite-element biophysical models created from structural magnetic resonance imaging and diffusion weighted imaging. The finite-element biophysical models will also be used to identify the initial RNS-TCN stimulation pathway and current amplitude. During the blinded evaluation period patients will be randomized to receive either high-frequency short burst (HFSB) or low-frequency long burst (LFLB) RNS-TCN, then enter a washout period before crossing over to receive the other treatment condition. During the open label period stimulation parameters can be modified at the discretion of the physician. Parameter adjustments will be informed by using a Bayesian optimization model developed for specifically for each patient. All clinical and electrophysiological data collected during the study will be used to identify a biomarker of clinical response; if found, these will aid future epilepsy research and clinical practice. If safety is favorable and there is preliminary evidence for efficacy, then this early experience will inform the design of a future larger feasibility study. In addition to treating a population in need, this project engages in fundamental discovery of biomarkers in generalized network epilepsies, and develops novel automated therapy selection policies that have the potential to improve the lives of patients with LGS and other seizure disorders.

项目摘要 /摘要 Lennox-Gastaut综合征（LGS）是一种毁灭性的童年发作性癫痫的形式功能障碍和经常概括的发作癫痫发作（GO）经常导致受伤。由于缺乏有效的疗法以及脑反应刺激的安全性和有效性顽固性局灶性发作癫痫发作（FOS），这项研究将测试脑反应性神经刺激是否丘脑皮质网络（RNS-TCN）是治疗LGS的可行策略。具体而言，该项目的目的是：（1）获得有关使用RNS-TCN治疗LGS的安全性和效率的初步证据；（2）创建一个基于患者特定的计算网络模型的交互式治疗决定支持系统和机器学习以识别最佳的铅位置和刺激参数。使用FDA批准用于FOS的RNS®系统，将进行早期可行性IDE研究在20名LGS患者和医学上棘手的GO患者中，有6个癫痫中心。患者将入学两个队列的10个队列，在第一个队列中具有安全性和效率里程碑队列。患者将在丘脑的centromedian核心中双侧放置两个深度铅双侧两侧放置在培养基前额叶皮层上。选择这些目标是因为它们在LGS中的发作和传播中暗示。线索将位于每个目标中，以便刺激最大地参与丘脑皮质网络，在有限元生物物理模型的指导下由结构磁共振成像和扩散加权成像产生。有限元生物物理模型还将用于识别初始RNS-TCN模拟途径和电流放大器。在盲评估期间，患者将随机分配以接受高频短爆发（HFSB）或低频长爆发（LFLB）RNS-TCN，然后进入冲洗期，然后越过接受其他治疗条件。在开放标签期间，刺激参数可以在身体自由裁量权。参数调整将通过使用贝叶斯优化来告知专门为每个患者开发的模型。在此期间收集的所有临床和电生理数据研究将用于识别临床反应的生物标志物；如果发现，这些将有助于未来的癫痫研究和临床实践。如果安全有利并且有效率的初步证据，那么经验将为未来更大的可行性研究的设计提供信息。除了治疗有需要的人群之外，该项目还从事生物标志物的基本发现广义网络发作，并制定具有具有的新型自动化治疗选择政策改善LGS患者和其他癫痫发作障碍患者的生活的潜力。