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:10414867
- 负责人:
- 金额:$ 259.68万
- 依托单位:
- 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:
- 关键词:12 year oldAdverse effectsBilateralBiological MarkersBlindedBrainCentromedian Thalamic NucleusChildhoodClinicalClinical ResearchClonic SeizureComputer ModelsCrossover DesignDataDecision Support SystemsDeep Brain StimulationDetectionDevice DesignsDevicesDiffusion Magnetic Resonance ImagingDiseaseElectrodesElectroencephalographyElectrophysiology (science)ElementsEnrollmentEpilepsyEtiologyEvaluationFDA approvedFeasibility StudiesFollow-Up StudiesFrequenciesFunctional disorderFutureGastaut syndromeGeneralized EpilepsyGenetic Crossing OverGoalsImpaired cognitionImplantInjuryIpsilateralLeadLongterm Follow-upMachine LearningMagnetic Resonance ImagingManualsMedialMedicalMedical ImagingMental DepressionModelingNeuronsOnline SystemsOperative Surgical ProceduresOutcomeParkinson DiseasePathway interactionsPatientsPharmaceutical PreparationsPhysiciansPilot ProjectsPoliciesPopulationPost-Traumatic Stress DisordersPrefrontal CortexRandomizedResearchSafetySeizuresSelection for TreatmentsSingle-Blind StudySystemTestingTimeTonic SeizuresUpdateaddictionatonic seizurebasebiomarker discoverybiophysical modelblindclinical efficacyclinical practicecohortcomputational network modelingdesigndiariesearly experienceeffective therapyimprovedinteractive therapylead optimizationmachine learning methodmortalityneuroimagingneurophysiologyneuroregulationnovelopen labelpotential biomarkerpredict clinical outcomeprototyperecruitresponsesafety testingtool
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.
项目概要/摘要
Lennox-Gastaut 综合征 (LGS) 是一种破坏性的儿童期癫痫发作,伴有认知障碍
功能障碍和非常频繁的全身性癫痫发作(GOS)通常会导致受伤。在缺乏的推动下
有效的治疗方法以及已证实的脑反应刺激在医学上的安全性和有效性
顽固性局灶性癫痫发作(FOS),本研究将测试大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。具体来说,该项目旨在:
(1) 获得 RNS-TCN 治疗 LGS 的 GOS 的安全性和有效性的初步证据; (2) 创建一个
基于患者特定计算网络模型的交互式治疗决策支持系统
机器学习来识别最佳引线放置和刺激参数。
使用经 FDA 批准用于 FOS 的 RNS® 系统,将进行早期可行性 IDE 研究
在 6 个癫痫中心治疗了 20 名 LGS 和难治性 GOS 患者。患者将被纳入
两组各 10 人,第一组的安全性和有效性里程碑控制第二组的入组
队列。患者将在两侧丘脑中心正中核放置两根深度导线,
两条硬膜下带状引线双侧放置在内侧前额皮质上。选择这些目标是因为
它们与 LGS 中 GOS 的发病和传播有关。线索将位于每个目标内,以便
在有限元生物物理模型的指导下,刺激最大程度地参与丘脑皮质网络
由结构磁共振成像和扩散加权成像创建。有限元
生物物理模型还将用于识别初始 RNS-TCN 刺激路径和电流幅度。
在盲法评估期间,患者将被随机分配接受高频短脉冲
(HFSB)或低频长突发(LFLB)RNS-TCN,然后在交叉到之前进入清洗期
接受其他治疗条件。在开放标签期间,可以修改刺激参数
医生的酌情权。将通过使用贝叶斯优化来通知参数调整
专为每位患者开发的模型。期间收集的所有临床和电生理数据
研究将用于确定临床反应的生物标志物;如果找到的话,这些将有助于未来的癫痫研究
和临床实践。如果安全性良好并且有初步证据证明疗效,那么尽早
经验将为未来更大规模的可行性研究的设计提供信息。
除了治疗有需要的人群外,该项目还致力于生物标志物的基础发现
广泛性网络癫痫,并开发了新颖的自动化治疗选择策略
改善 LGS 和其他癫痫病患者的生活的潜力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MARTHA J MORRELL其他文献
MARTHA J MORRELL的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MARTHA J MORRELL', 18)}}的其他基金
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
- 批准号:
10615330 - 财政年份:2021
- 资助金额:
$ 259.68万 - 项目类别:
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
- 批准号:
9958791 - 财政年份:2021
- 资助金额:
$ 259.68万 - 项目类别:
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
- 批准号:
10674542 - 财政年份:2021
- 资助金额:
$ 259.68万 - 项目类别:
Reproductive Function in Women with Bipolar Disorders
双相情感障碍女性的生殖功能
- 批准号:
7045027 - 财政年份:2003
- 资助金额:
$ 259.68万 - 项目类别:
EFFECTS OF ANTIEPILEPTIC DRUGS ON BONE TURNOVER AND MASS
抗癫痫药物对骨转换和质量的影响
- 批准号:
6567729 - 财政年份:2001
- 资助金额:
$ 259.68万 - 项目类别:
EFFECTS OF ANTIEPILEPTIC DRUGS ON BONE TURNOVER AND MASS
抗癫痫药物对骨转换和质量的影响
- 批准号:
6468469 - 财政年份:2000
- 资助金额:
$ 259.68万 - 项目类别:
HYPOTHALAMIC-PITUITARY-OVARIAN AXIS IN WOMEN WITH EPILEPSY
女性癫痫患者的下丘脑-垂体-卵巢轴
- 批准号:
6115032 - 财政年份:1998
- 资助金额:
$ 259.68万 - 项目类别:
ANALYSIS OF BONE HEALTH IN AED EXPOSED WOMEN WITH EPILEPSY
暴露于 AED 的癫痫女性的骨骼健康分析
- 批准号:
6115081 - 财政年份:1998
- 资助金额:
$ 259.68万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 259.68万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 259.68万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 259.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 259.68万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 259.68万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 259.68万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 259.68万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 259.68万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 259.68万 - 项目类别:
Downsides of downhill: The adverse effects of head vibration associated with downhill mountain biking on visuomotor and cognitive function
速降的缺点:与速降山地自行车相关的头部振动对视觉运动和认知功能的不利影响
- 批准号:
2706416 - 财政年份:2022
- 资助金额:
$ 259.68万 - 项目类别:
Studentship