The role of genetic polymorphisms in the CNS transport of endogenous metabolites and drugs in intensive care medicine.

• Conditions: I61; S06; I60; G91; G93; Intracerebral haemorrhage; Intracranial injury; Subarachnoid haemorrhage; Hydrocephalus; Other disorders of brain

• Registration Number: DRKS00034342
• Lead Sponsor: niversitätsmedizin Göttingen, Institut für klinische Pharmakologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-29
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Intensive care patients who have received an external cerebrospinal fluid drainage (EVD or LD) due to acute brain injury.
2. Consent from the patient or their legal representative. If a legal representative is not available at the time of study inclusion, inclusion can be carried out under the assumption of presumed will due to the minimal risk and minimal burden of the study-related measures. As soon as the patient is responsive again or a guardian or healthcare proxy is available, they will be asked for consent. If consent is denied, the data and biomaterials of the affected patient will not be used further.

Exclusion Criteria

1. Exclusively palliative treatment due to a poor prognosis, expected survival < 48 hours.
2. Refusal to participate in the study by the patient or by the guardian.
3. Refusal of intensive medical care.

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Cerebrospinal fluid and plasma concentrations of endogenous metabolic products and medications, as far as possible from the course of treatment, at least at two-time points, as well as in case of significant changes in the patient's medication or clinical condition. We are interested in the ratio between cerebrospinal fluid concentration and blood concentration as an indicator of the substance-specific activity of the blood-brain barrier.<br>2. Inherited genomic variants and non-genetic parameters (mRNA expression, DNA methylation in peripheral blood) of the transport proteins expressed in the blood-brain barrier. In the first step, we would focus on the analysis of genetic polymorphisms with an allele frequency of at least 5%, but subsequently, we would also analyze all other transport proteins with clinically significant genetic polymorphisms with relevant epidemiological prevalence.

Secondary Outcome Measures

Name	Time	Method
1. Identification of biomarkers with good sensitivity and specificity for blood-brain barrier disruption.<br>2. Relationship between genetic polymorphisms, the ratios of blood-to-cerebrospinal fluid concentrations, and the clinical course of intensive care patients.