Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage

Conditions

• Post-hemorrhagic Hydrocephalus (PHH)

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Sirolimus (Rapamune®) — DRUG
  Ventricular delivery

Study Details

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.

Key Dates

Start date

Jan 1, 2027

Status verified

Jun 2026

Primary completion

Dec 31, 2027

Completion

Dec 31, 2027

Study Design

Enrollment

15 participants (estimated)

Allocation

NA

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
  We 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.

Primary Outcome Measure

CSF rapamycin concentration [ Time Frame: Baseline, 7 days, and 14 days after rapamycin treatment. ]

Central Contacts

• Kristopher Kahle, M.D., Ph.D.
  14143057506
  [email protected]
• Carla Fortes, BA
  16175489679
  [email protected]

Locations (1)

Find similar trials in Boston, MA

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