VENTURE-PHH: Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
研究概览
简要总结
Hydrocephalus is a serious condition in which fluid builds up inside the brain, often requiring lifelong surgical placement of a shunt to drain excess cerebrospinal fluid (CSF). One of the most common causes of hydrocephalus is bleeding into the brain's fluid spaces after aneurysm rupture, prematurity, or infection. Currently, no medication exists to prevent hydrocephalus from developing after these injuries. The investigators' recent research suggests that hydrocephalus may result not only from blocked fluid pathways but also from harmful inflammation within the brain's ventricular system. The investigators discovered that inflammation activates the choroid plexus, the tissue that produces CSF, causing excessive CSF production and inflammatory injury to the ventricular lining and surrounding brain tissue. The investigators also identified inflammatory biomarkers and extracellular vesicles in human CSF that may enable real-time monitoring of these disease processes.
In this project, the investigators will perform a first-in-human pilot study testing whether targeted "intraventricular mTOR inhibition" can reduce ventricular inflammation and prevent hydrocephalus after severe brain hemorrhage. The medication will be delivered via temporary ventricular drains already in place as part of routine clinical care. The investigators will study safety, inflammation, CSF production, brain imaging changes, and whether patients ultimately require permanent shunts. Although this initial study focuses on adults with hemorrhage-related hydrocephalus, our long-term goal is to develop non-surgical therapies that could help children with hydrocephalus caused by prematurity or infection, especially in regions where access to neurosurgical care and shunt surgery is limited.
详细描述
Hydrocephalus remains one of the most common neurosurgical disorders worldwide and is currently treated primarily with surgical diversion of CSF using implanted shunts. Although lifesaving, shunts frequently fail, require repeated surgeries, and do not directly address the underlying biological injury occurring within the brain and ventricular system. Many patients continue to experience lifelong neurological complications despite surgical treatment. This project has the potential to shift hydrocephalus treatment from surgical management toward mechanism-guided prevention. By targeting ventricular inflammation early after hemorrhage, the investigators aim to prevent the biological processes that drive excessive CSF accumulation, ventricular remodeling, ependymal injury, and chronic inflammatory scarring. Successful completion of this work could establish the first pharmacologic strategy designed to prevent hydrocephalus rather than simply treat its consequences after it develops.
The impact of this approach could extend far beyond adult hemorrhage-related hydrocephalus. Similar inflammatory mechanisms are believed to contribute to hydrocephalus caused by prematurity, infection, and traumatic brain injury. In particular, post-infectious and neonatal hydrocephalus remain major causes of childhood disability and death in many low-resource regions where access to shunt surgery and specialized neurosurgical care is limited. A scalable medical therapy capable of reducing hydrocephalus progression could therefore have a substantial global health impact. In addition, this project establishes a new translational framework for studying the ventricular neuroimmune microenvironment through real-time analyses of CSF biomarkers and extracellular vesicles. These tools may ultimately enable personalized monitoring and targeted treatment approaches for multiple forms of hydrocephalus and related neuroinflammatory disorders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH)
- •Hunt Hess grade IV to V
- •Radiographic evidence of intraventricular hemorrhage (IVH)
- •Clinically indicated EVD placement as part of standard neurocritical care
- •Ability to enroll during the acute post-hemorrhagic inflammatory period, ideally within 24 hours of EVD placement
排除标准
- •Pre-existing ventriculoperitoneal shunt dependence
- •Severe baseline immunosuppression
- •Uncontrolled systemic infection unrelated to hemorrhage
- •Pregnancy
- •Anticipated withdrawal of life-sustaining therapy within 24 hours
- •Inability to safely receive investigational ventricular therapy
研究组 & 干预措施
Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
The investigators will conduct a prospective, single-center, phase Ib/IIa, biomarker-rich translational pilot study evaluating intraventricular mTOR inhibition in adults with severe aneurysmal subarachnoid hemorrhage (aSAH) who require external ventricular drain (EVD) placement as part of routine neurocritical care management. The central objective of the study is to determine whether early modulation of ventricular immune-secretory signaling is feasible, biologically active, and capable of altering inflammatory CSF physiology and ventricular remodeling following hemorrhage.
干预措施: Sirolimus (Rapamune®) (Drug)
研究者
Kristopher Kahle
Nicholas T. Zervas Endowed Chair and Associate Professor of Neurosurgery
Massachusetts General Hospital