# Development of biomarkers to optimize intrathecal nicardipine treatment for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $375,235

## Abstract

Project Summary/Abstract
Subarachnoid hemorrhage is a devastating type of stroke wherein a ruptured blood vessel
leads to blood in the subarachnoid space around the brain. Cerebral vasospasm, i.e.,
aberrant constriction of brain blood vessels, occurs in ~30% of patients after
subarachnoid hemorrhage and can lead to delayed cerebral ischemia following the initial
SAH. Delayed cerebral ischemia is a main contributor to patient survival and long-term
functional outcome. Unfortunately, therapeutic strategies to treat vasospasm and prevent
delayed ischemia are lacking. In 2010 Emory University Hospital implemented intrathecal
nicardipine, a calcium channel blocker that acts to dilate the cerebrovasculature, as a
treatment for subarachnoid hemorrhage patients with suspected vasospasm. Our
preliminary retrospective results from >400 patients showed that intrathecal nicardipine
has a low rate of complications, is effective at inducing macrovascular vasodilation, and
reduces the risk of delayed cerebral ischemia. However, selecting patients for this
treatment, as well as estimating the benefit for the individual subject is still lacking. Our
overall objective is to develop biomarkers of outcome after SAH that can help optimize
treatment strategies and improve outcomes. Non-invasive diffuse optical spectroscopies
(DOS) show promise to provide such biomarkers. In preliminary data with DOS in 20 SAH
patients, we found that the cerebral blood flow response to the first dose of IT nicardipine
was significantly different in patients who developed DCI versus those who did not.
Specifically, cerebral blood flow increased in patients who did not go on to develop DCI
(as expected), whereas those who developed DCI showed a lack of response or decrease
in blood flow after treatment (paradoxical response). These promising data suggest that
DOS may provide valuable insights into the microvascular environment in SAH patients
that could be used to guide treatment and improve outcomes. Furthermore, preliminary
data suggest that the pharmacokinetics of IT nicardipine may provide an alternative
biomarker of target therapeutic nicardipine concentrations in the cerebrospinal fluid.
Building on this promising data, in this proposal we will determine early, non-invasive
optical biomarkers of cerebrovascular hemodynamics associated with development of
delay cerebral ischemia (Aim 1), and we will prospectively determine the relationship
between IT nicardipine pharmacokinetics in the cerebrospinal fluid and outcome (Aim 2).

## Key facts

- **NIH application ID:** 10908464
- **Project number:** 5R01NS130036-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Ofer Sadan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,235
- **Award type:** 5
- **Project period:** 2022-09-27 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908464

## Citation

> US National Institutes of Health, RePORTER application 10908464, Development of biomarkers to optimize intrathecal nicardipine treatment for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage (5R01NS130036-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908464. Licensed CC0.

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