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Cerebral Nimodipine Concentrations Following Oral, Intra-venous and Intra-arterial Administration

NCT04649398 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 30

Last updated 2023-10-19

No results posted yet for this study

Summary

Nimodipine reduces the risk of poor outcome and delayed cerebral ischemia in patients suffering aneurysmal subarachnoid haemorrhage (SAH), but its mode of action is unknown. Its beneficial effect is assumed to be due its neuroprotective effects by reducing intracellular calcium and thereby cellular apoptosis, but higher concentrations might induce marked systemic hypotension, thereby inducing cerebral ischemia. Since several dosing regimes and routes of administration with inconclusive superiority exist and since the target site concentration of nimodipine - the unbound drug concentrations beyond the blood-brain barrier - is still not known, it is reasonable to measure nimodipine concentrations within the blood, cerebrospinal fluid (CSF) and interstitial brain tissue following oral, intra-venous and intra-arterial administration and correlate intra-arterial nimodipine administration to measures of cerebral metabolism and oxygenation.

Therefore, the investigators propose to investigate in 30 patients suffering severe aneurysmal SAH and requiring cerebral microdialysis for cerebral neurochemical monitoring:

* the ability of nimodipine to penetrate into the brain of neurointensive care patients by comparing exposure in brain, CSF and plasma, dependent on the route of administration (i.e. oral, intra-venous, and intra-arterial) and dosing intra-venously (0.5 - 2mg/h)
* the impact of orally, intra-venously, and intra-arterially delivered nimodipine on cerebral metabolism, i.e. lactate/pyruvate ratio, pbtO2 and transcranial doppler flow velocities
* the effect of oral and intra-venous nimodipine on systemic hemodynamic and cardiac parameters, using continuous Pulse Contour Cardiac Output (PiCCO) monitoring
* the penetration properties of ethanol - as an excipient of nimodipine infusion - into the brain by comparing exposure in brain, CSF and plasma and quantifying the neuronal exposure to alcohol dependent on blood levels

Conditions

  • Subarachnoid Hemorrhage, Aneurysmal
  • Delayed Cerebral Ischemia
  • Vasospasm, Cerebral

Interventions

DRUG

Nimodipine

If application of nimodipine is clinically indicated patients will be enrolled in the study protocol according to the inclusion and exclusion criteria. The clinically appropriate route of administration will be administered according to the recommended regimen of the study drug; i.e. within the first 10-14 days intra-venous infusion and thereafter oral administration. Intra-arterial infusion will be performed due to severe cerebral vasospasm with impending stroke.

Sponsors & Collaborators

  • University of Vienna

    collaborator OTHER

  • Austrian Science Fund (FWF)

    collaborator OTHER

  • Medical University of Vienna

    lead OTHER

Eligibility

Min Age
18 Years
Max Age
95 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-11-25
Primary Completion
2024-07-31
Completion
2025-12-31
FDA Drug
Yes

Countries

  • Austria

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04649398 on ClinicalTrials.gov