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Multimodal Neuromonitoring (MMNM)

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ClinicalTrials.gov Identifier: NCT04737369
Recruitment Status : Recruiting
First Posted : February 3, 2021
Last Update Posted : February 3, 2021
Sponsor:
Collaborator:
Karl Landsteiner Institute for Clinical Epilepsy Research
Information provided by (Responsible Party):
Johannes Herta, Medical University of Vienna

Study Description
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

Theoretical Framework & Background

Cortical spreading depressions (CSD) and seizures, are crucial in the development of delayed cerebral ischemia and poor functional outcome in patients suffering from acute brain injuries such as subarachnoid hemorrhage. Multimodal neuromonitoring (MMNM) provides the unique possibility in the sedated and mechanically ventilated patients to record these electrophysiological phenomena and relate them to measures of cerebral ischemia and malperfusion. MMNM combines invasive (e.g. electrocorticography, cerebral microdialysis, brain tissue oxygenation) and noninvasive (e.g. neuroimaging, continuous EEG) techniques. Additionally, cerebral microdialysis can measure the unbound extracellular drug concentrations of sedatives, which potentially inhibit CSD and seizures in various degrees, beyond the blood-brain barrier without further interventions.

Hypotheses

  1. Online multimodal neuromonitoring can accurately detect changes in neuronal metabolic demand and pathological neuronal bioelectrical changes in highly vulnerable brain tissue.
  2. Online multimodal neuromonitoring can accurately detect the impact of pathological neuronal bioelectrical changes on metabolic demand in highly vulnerable brain tissue.
  3. The occurrence and duration of pathological neuronal bioelectrical changes are dependent on sedatives and antiepileptic drug concentrations
  4. The occurrence and duration of pathological neuronal bioelectrical changes have a negative impact on functional and neurological long-term patient outcome.
  5. Simultaneous invasive and non-invasive multimodal neuromonitoring can identify a clear relationship of both methods regarding pathological neuronal bioelectrical changes and metabolic brain status.

Methods

Systematic analysis of MMNM measurements following standardized criteria and correlation of electrophysiological phenomena with cerebral metabolic changes in all included patients. In a second step neuroimaging, cerebral extracellular sedative drug concentrations and neurological functional outcome, will be correlated with both electrophysiologic and metabolic changes. Due to numerous high-resolution parameters, machine learning algorithms will be used to correlate comprehensive data on group and individual levels following a holistic approach.

Level of originality

Extensive, cutting edge diagnostic methods are used to get a better insight into the pathophysiology of electrophysiological and metabolic changes during the development of secondary brain damage. Due to the immense amount of high-resolution data, a computer-assisted evaluation will be applied to identify relationships in the development of secondary brain injury. For the first time systematic testing of several drug concentrations beyond the blood-brain barrier will be performed. With these combined methods, we will be able to develop new cerebroprotective treatment concepts on an individual basis.


Condition or disease
Subarachnoid Hemorrhage Intracerebral Hemorrhage Traumatic Brain Injury Cortical Spreading Depolarization and Depression Seizures Ictal-Interictal Continuum

Study Design
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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Multimodal Neuromonitoring: an Explorative Study in Neurocritical Care Patients
Actual Study Start Date : December 1, 2020
Estimated Primary Completion Date : December 1, 2025
Estimated Study Completion Date : December 1, 2025
Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Count of SD during electrocorticography [ Time Frame: up to 21 days ]
    Count of cortical spreading depolarization (SD) during continuous electrocorticography

  2. Daily pattern duration of CSD during electrocorticography [ Time Frame: up to 21 days ]
    Duration of cortical spreading depression (CSD) per hour during continuous electrocorticography

  3. Daily pattern duration of NCSE during electrocorticography [ Time Frame: up to 21 days ]
    Duration of nonconvulsive status epilepticus (NCSE) per hour during continuous electrocorticography

  4. Daily pattern duration of RPPIIC during electrocorticography [ Time Frame: up to 21 days ]
    Duration of rhythmic or periodic EEG patterns on the ictal-interictal continuum (RPPIIC) per hour during continuous electrocorticography

  5. Daily duration of metabolic crisis [ Time Frame: up to 21 days ]
    Duration of metabolic crisis (defined as Lactate Pyruvate ratio [LPR] > 40 and lactate higher than 4 mmol/l) during continuous electrocorticography

  6. Daily duration of mitochondrial dysfunction [ Time Frame: up to 21 days ]
    Duration of mitochondrial dysfunction (defined as LPR > 40, Pyruvate > 70 μmol/l and partial brain tissue oxygenation [PbtO2] > 20 mmHg) during continuous electrocorticography

  7. Daily duration of ischemia [ Time Frame: up to 21 days ]
    Duration of ischemia (defined as PbtO2 < 15 mmHg and cerebral perfusion pressure [CPP] < 60 mmHg) during continuous electrocorticography

  8. Daily duration of elevated intracranial pressure (ICP) [ Time Frame: up to 21 days ]
    Duration of elevated intracranial pressure (defined as ICP > 22 mmHg) during continuous electrocorticography

  9. Neuropharmacology Cmax) [ Time Frame: up to 21 days ]
    Cmax of routinely used sedative drug concentrations in blood and brain (Esketamine, Midazolam and Propofol)

  10. Neuropharmacology (AUC) [ Time Frame: up to 21 days ]
    AUC of routinely used sedative drug concentrations in blood and brain (Esketamine, Midazolam and Propofol)

  11. Neuropharmacology (t1/2) [ Time Frame: up to 21 days ]
    t1/2 of routinely used sedative drug concentrations in blood and brain (Esketamine, Midazolam and Propofol)

  12. Neuroimaging [ Time Frame: up to 28 days ]
    Absence or presence of hypoperfusion or ischemic infarctions in neuroimaging

  13. Functional patient outcome [ Time Frame: up to 6 months ]
    modified Rankin Scale


Biospecimen Retention:   Samples Without DNA
Microdialysis Samples

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Individuals between 18-80 years with poor grade aneurysmal SAH (World Federation Neurosurgical Societies >3), severe ICH (ICH Score >3) or severe TBI (Glasgow Coma Scale <9).
Criteria

Inclusion Criteria:

  • Individuals between 18-80 years with poor grade aneurysmal SAH (World Federation Neurosurgical Societies >3), severe ICH (ICH Score >3) or severe TBI (Glasgow Coma Scale < 9). The diagnosis of SAH, ICH and TBI will be established by computed tomography (CT).
  • Individuals that are unlikely to regain consciousness within the following 48 hours.
  • Individuals that are expected to survive for the next 48 hours.

Exclusion Criteria:

  • Individuals younger than 18 years old and older than 80 years.
  • Pregnant women (documented via positive ß-HCG test).
  • Patients, who do not want to participate in the study. As the patient is not able to consent prior to the study, information about the study details will be given to the patient in case of clinical improvement. The patient information sheet will be handed out.

Thereafter, the patient has the possibility to withdraw permission of study-participation.

Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04737369


Contacts
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Contact: Johannes Herta, MD PhD +43 (0)1 40400-25770 johannes.herta@meduniwien.ac.at
Contact: Johannes Koren, MD PhD +43 (0)1 80110-2524 johannes.koren@meduniwien.ac.at

Locations
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Austria
Department of Neurosurgery, Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Johannes Herta, MD PhD    +43 (0)1 40400-25770    johannes.herta@meduniwien.ac.at   
Contact: Johannes Koren, MD PhD    +43 (0)1 80110-2524    johannes.koren@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
Karl Landsteiner Institute for Clinical Epilepsy Research
Investigators
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Principal Investigator: Johannes Herta, MD PhD Department of Neurosurgery, Medical University of Vienna
More Information
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Responsible Party: Johannes Herta, Principle Investigator, Co-Head of the Neurosurgical ICU, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT04737369    
Other Study ID Numbers: MMNM01
First Posted: February 3, 2021    Key Record Dates
Last Update Posted: February 3, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johannes Herta, Medical University of Vienna:
Multimodal Neuromonitoring
Electrocorticography
Cerebral Microdialysis
Neuropharmacology
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Seizures
Subarachnoid Hemorrhage
Cerebral Hemorrhage
Hemorrhage
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Pathologic Processes
Neurologic Manifestations
Intracranial Hemorrhages
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases