Linearity and Non-linearity of Cerebral Autoregulation

August 25, 2022 updated by: Martin Müller, Luzerner Kantonsspital

Injured brain tissue supplied by a disturbed state of cerebral autoregulation (CA) is at risk of secondary ischemia, e.g. in patients with stroke, subarachnoid hemorrhage, intracerebral hemorrhage or bacterial Meningitis. Up to now, there is lack of a simple and easy to perform bed side test that would allow for to intervene when CA failure is indicated. For this purpose, we explore the dynamics of the interplay between blood pressure and cerebral blood flow velocity using transcranial Doppler ultrasound (or near infrared spectroscopy derived haemoglobin concentration changes) as a measure of CA. To describe these dynamics different mathematical models are used, but they all still need validation and proof of concept because these dynamics are poorly understood with respect to the factors which influence the composition of the mathematical models.

Objectives: To what amount is CA disturbed in the different stroke subgroups ? Is a disturbed CA a risk factor of poorer outcome ?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

We investigate which factors determine the dynamics of CA under the assumption that disturbed dynamics of the relation blood pressure (BP) - cerebral blood flow velocity CBFv) indicate a disturbed CA. Factors to be considered relevant are BP, blood carbon dioxide (CO2) concentration (measured as endtidal CO2 concentration), autonomic nervous system function such as heart rate, pulse pressure amplitude and baroreflex sensitivity, movement or psychological tasks, and in the patients the kind and the severity of the underlying disease. Via different mathematical models the effects of these variables on CBFv as the Output function is evaluated. The most frequently used approach is the use of Transfer functions.

In the registry will include the patients with acute strokes hospitalized at our stroke center. We will include every stroke patient with any Kind and severity of stroke syndromes who gives informed consent and who has a so called temporal ultrasound window to insonate the middle cerebral artery. BP will be measure noninvasively by a Finapres device. Items registered are Age, gender, cerebrovascular risk factors, temperature, mean BP and ist variability on days 1-3, stroke classification using TOAST, Perfusion Computed Tomography and MRI, and at the time of the simultaneous recordings of CBFv and BP the endtidal CO2, mean BP, mean pulsatility index, and after Transfer function analysis coherence, gain and Phase in different frequency ranges

Study Type

Observational

Enrollment (Anticipated)

580

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Stroke patients: all stroke patients which will be referred to our stroke Center aged 18 years or older. N=500.

Healthy controls of all ages above 18 years. N=80

Description

Inclusion Criteria:

  • every typ of ischemic stroke of any severity
  • presence of a "temporal bone window"

Exclusion Criteria:

  • Age < 18 years,
  • pregnancy
  • no informed consent.
  • absence of a "temporal bone window"

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with stroke
Patients with stroke of all subtypes, with and without different Kind of Lysis therapy
Diagnostic test: Assessment of CA
As part of our routine stroke work up, each patient receives an initial CT scan with CT perfusion to indicate thrombolysis therapy (intravenous, mechanical, or both, depending on the time since first stroke symptoms and perfusion-mismatch), an MRI within 2 days, extracranial and transcranial Duplex ultrasound, echocardiography, continuous Monitoring of BP, O2, body temperature, NIHSS and Glagow Coma Scale (GCS) every 6 hours. Assessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates
Controls
Healthy controls of all Ages above 18 years
Diagnostic test: Assesment of CA only
Assessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of modified Rankin Scale (mRs) : 0, no symptoms. 1, no significant disability. 2, slight disability. 3, moderate disability. 4, moderate severe disability. 5, severe disability. 6, dead
Time Frame: 3 months
Clinical outcome
3 months
State of cerebral autoregulation (CA)
Time Frame: Assessment on days 1-3 after stroke onset
Transfer function estimates (gain, phase) between low frequency oscillations in BP and CBFv. A low gain and a high phase indicate good CA, a high gain and a low phase a poor CA state. Typically, a phase of 1 radian indicates a good CA, a phase of 0.2 a very poor one.
Assessment on days 1-3 after stroke onset

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Luzerner Kantonsspital

Investigators

  • Principal Investigator: Martin Müller, MD, Luzerner Kantonsspital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2020

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

October 21, 2020

First Submitted That Met QC Criteria

October 27, 2020

First Posted (Actual)

November 2, 2020

Study Record Updates

Last Update Posted (Actual)

August 26, 2022

Last Update Submitted That Met QC Criteria

August 25, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PB_2016-01719

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

retrospective data collection for an individual participant data metaanalysis as published in Int J Stroke. 2020 Oct;15(7):807-812. doi: 10.1177/1747493020907003

IPD Sharing Time Frame

2021 - 2025

IPD Sharing Access Criteria

on request to M Müller

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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