A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial

INPH 分流 (PENS) 试验中安慰剂对照的有效性

• 批准号: 10279146
• 负责人: Richard Holubkov
• 金额: $ 305.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10279146
• 关键词: Adult; Affect; Age-Years; Algorithms; Alzheimer' s Disease; Amyloid beta-42; Anatomy; Biological Markers; Bladder Control; Blinded; Blood Vessels; Brain; Cephalic; Cerebrospinal fluid shunts procedure; Clinical; Clinical effectiveness; Cognition; Cognitive; Collaborations; Controlled Clinical Trials; Creation of ventriculo-peritoneal shunt; Data; Data Collection; Dementia; Devices; Diagnosis; Disease; Effectiveness; Elderly; Enrollment; Equilibrium; Excision; FDA approved; Future; Gait; Goals; Guidelines; Health; Health Expenditures; Hydrocephalus; Image; Impaired cognition; Impairment; Lead; Liquid substance; Magnetic Resonance Imaging; Measures; Medical; Methods; Morbidity - disease rate; Neurologist; Neurology; Neuropsychological Tests; Neuropsychology; Neurosurgeon; Normal Pressure Hydrocephalus; Operative Surgical Procedures; Outcome; Outcome Assessment; Outcome Measure; Participant; Patient Selection; Patients; Pattern; Persons; Physiological; Placebo Control; Placebo Effect; Placebos; Population; Prevalence; Randomized; Randomized Clinical Trials; Reporting; Research; Research Proposals; Risk; Running; Shunt Device; Site; Subgroup; Surveys; Symptoms; System; Testing; Treatment Effectiveness; Uncertainty; Uncontrolled Study; Urinary Incontinence; Ventricular; Work; active method; aging population; base; biomarker identification; brain surgery; clinical outcome measures; comparison group; cost; disability; early experience; effective therapy; fluid flow; health care service; imaging biomarker; implantation; micturition urgency; neurodegenerative dementia; older patient; patient biomarkers; placebo controlled study; placebo controlled trial; placebo group; primary endpoint; primary outcome; programs; prospective; randomized placebo-controlled clinical trial; recruit; response; secondary analysis; secondary outcome; success; tau Proteins; treatment effect; virtual

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a reversible form of dementia and gait imbalance in the elderly that has been treated with surgical ventriculoperitoneal shunting (VPS). Although VPS has been performed for decades, the effectiveness of VPS has not been tested in an appropriately run placebo-controlled clinical trial. Due to the lack of data from placebo-controlled trials, skepticism about VPS in the elderly has significantly limited its use. The primary goal of this research proposal is to gather data with the goal of a definitive answer on the question of whether shunt surgery offers a benefit to patients with iNPH. We will accomplish this through a prospective, blinded, randomized placebo-controlled clinical trial that uses a contemporary FDA approved adjustable shunt system. This valve allows a “virtual off” setting allowing for noninvasive and reversible assignment of patients to treatment with a functioning (active group) or non- functioning (placebo group) shunt. The trial will enroll 100 iNPH patients at 20 sites. Participants selected for shunt surgery will be chosen based on standard and widely used iNPH guidelines. The trial is a delayed treatment paradigm where all 100 patients will receive the same surgery and device, differing only in the initial valve setting (active or placebo). The Primary analysis will be a group comparison of change from baseline in gait velocity at three months after implantation. Secondary analysis will measure balance, cognition, and bladder control. Three months after implantation, all participants in both groups are blindly adjusted to the active setting and followed for 9 months. A secondary goal of the study is to evaluate clinical, imaging, and CSF biomarkers before surgery to identify associations with subsequent shunt response. MR imaging and extended neuropsychological testing are also repeated after shunting to evaluate specific anatomical and cognitive domain changes that may be associated with gait changes. We expect that if we demonstrate the effectiveness of shunting in iNPH we will establish an effective treatment and facilitate an increase in appropriate iNPH shunting. In addition, the study of patient biomarkers associated with successful outcomes will allow future testing of algorithms for more accurate and efficient patient selection. Identification of subgroups of iNPH patients with improvement may also be suggested. Data from this controlled trial can ultimately benefit the 300 to 700 thousand iNPH patients in the US to receive an effective surgical treatment. If data shows that shunting is found to be ineffective in the placebo group, elderly patients will be spared the potential morbidity and cost of an ineffective brain surgery.

特发性正常压力脑积水（INPH）是一种可逆的痴呆症形式，并且在原来是通过手术室心室室内旋转（VPS）治疗的。尽管VPS进行了数十年，但VP的有效性尚未在适当运行的安慰剂对照临床试验中进行测试。由于缺乏安慰剂对照试验的数据，对古老的VPS的怀疑已大大限制了其使用。这项研究建议的主要目标是收集数据，其目标是关于分流手术是否对INPH患者有好处的问题的确切答案。我们将通过使用现代FDA批准的可调节分流系统的前瞻性，盲目，随机的安慰剂对照试验来实现这一目标。该阀允许“虚拟关闭”设置，允许患者进行非侵入性和可逆分配为具有功能的治疗（主动试验将在20个地点注册100名INPH患者。选择分流手术的参与者将根据标准和广泛使用的INPH指南选择。将在植入后三个月内对基线的群体进行比较。分流后还重复神经心理学测试，以评估可能与步态变化相关的特定解剖和认知领域变化。我们希望，如果我们证明在INPH中分流的有效性，我们将建立有效的治疗方法，并促进适当的INPH分流。此外，研究与成功结果相关的患者生物标志物的研究将允许对算法进行以后的测试，以进行更准确，有效的患者选择。也可以建议鉴定INPH患者的亚组。该对照试验的数据最终可以使美国300至70万INPH患者受益，以接受有效的手术治疗。如果数据表明在安慰剂组中发现shhun脚在安慰剂组中无效，那么老年患者将不利于无效的脑外科手术的潜在发病率和成本。