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

基本信息

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
项目类别：
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&apos 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

项目摘要

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) 是老年人痴呆和步态不平衡的一种可逆形式，可通过脑室腹腔分流术 (VPS) 进行治疗。尽管 VPS 已实施数十年，但 VPS 的有效性尚未经过适当的测试。由于缺乏安慰剂对照试验的数据，对老年人 VPS 的怀疑极大地限制了其使用。收集数据，以明确回答分流手术是否对 iNPH 患者有益的问题。我们将通过一项前瞻性、盲法、随机安慰剂对照临床试验来实现这一目标，该试验使用当代 FDA 批准的可调节分流系统。该阀门允许“虚拟关闭”设置，允许患者进行无创和可逆的分流治疗，该试验将在 20 日招募 100 名 iNPH 患者。选择进行分流手术的参与者将根据标准且广泛使用的 iNPH 指南进行选择，该试验是一种延迟治疗范例，所有 100 名患者将接受相同的手术和装置，仅在初始瓣膜设置（主动或安慰剂）方面有所不同。主要分析将是对植入后三个月步态速度相对于基线的变化进行分组比较，次要分析将测量植入后三个月的平衡、认知和膀胱控制，两组中的所有参与者都被盲目地调整到主动设置。并跟随该研究的第二个目标是在手术前评估临床、影像和脑脊液生物标志物，以确定与随后的分流反应的关联，并在分流后重复进行扩展的神经心理学测试，以评估可能发生的特定解剖和认知领域的变化。我们期望，如果我们证明 iNPH 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 分流的增加。此外，研究与成功结果相关的患者生物标志物。未来还可以对算法进行测试，以更准确、更有效地识别有改善的 iNPH 患者亚组，该对照试验的数据最终可以使美国 300 至 70 万 iNPH 患者接受有效的手术。如果数据显示安慰剂组中分流无效，老年患者将免受无效脑部手术的潜在发病率和费用。