Linearity and Non-linearity of Cerebral Autoregulation

NCT04611672 | Unknown

• 1 other identifier: PB_2016-01719
• Study Type: observational
• Target: 580
• Locations: 1 country
• Sites: 1

Brief Summary

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 ?

Conditions

Stroke, Acute

Keywords

Stroke, Cerebral autoregulation, Doppler, Carotid disease

Outcome Measures

Primary Outcomes (2)

• 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

  Clinical outcome

  3 months

• State of cerebral autoregulation (CA)

  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

Study Arms (2)

Patients with stroke

Patients with stroke of all subtypes, with and without different Kind of Lysis therapy

Diagnostic Test: Assessment of CA

Controls

Healthy controls of all Ages above 18 years

Diagnostic Test: Assesment of CA only

Interventions

Assessment of CA DIAGNOSTIC_TEST

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

Patients with stroke

Assesment of CA only DIAGNOSTIC_TEST

Assessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates

Controls

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Luzerner Kantonsspital: lead

Study Sites (1)

Kantonsspital Luzern

Lucerne, 6000, Switzerland

RECRUITING

Related Publications (8)

• Beishon L, Minhas JS, Nogueira R, Castro P, Budgeon C, Aries M, Payne S, Robinson TG, Panerai RB. INFOMATAS multi-center systematic review and meta-analysis individual patient data of dynamic cerebral autoregulation in ischemic stroke. Int J Stroke. 2020 Oct;15(7):807-812. doi: 10.1177/1747493020907003. Epub 2020 Feb 24.

  PMID: 32090712 BACKGROUND

• Meel-van den Abeelen AS, Simpson DM, Wang LJ, Slump CH, Zhang R, Tarumi T, Rickards CA, Payne S, Mitsis GD, Kostoglou K, Marmarelis V, Shin D, Tzeng YC, Ainslie PN, Gommer E, Muller M, Dorado AC, Smielewski P, Yelicich B, Puppo C, Liu X, Czosnyka M, Wang CY, Novak V, Panerai RB, Claassen JA. Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure-flow relation: the CARNet study. Med Eng Phys. 2014 May;36(5):620-7. doi: 10.1016/j.medengphy.2014.02.002. Epub 2014 Apr 13.

  PMID: 24725709 BACKGROUND

• Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB; international Cerebral Autoregulation Research Network (CARNet). Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network. J Cereb Blood Flow Metab. 2016 Apr;36(4):665-80. doi: 10.1177/0271678X15626425. Epub 2016 Jan 18.

  PMID: 26782760 BACKGROUND

• Muller M, Osterreich M, Lakatos L, Hessling AV. Cerebral macro- and microcirculatory blood flow dynamics in successfully treated chronic hypertensive patients with and without white mater lesions. Sci Rep. 2020 Jun 8;10(1):9213. doi: 10.1038/s41598-020-66317-x.

  PMID: 32514031 RESULT

• Muller M, Osterreich M, von Hessling A, Smith RS. Incomplete recovery of cerebral blood flow dynamics in sufficiently treated high blood pressure. J Hypertens. 2019 Feb;37(2):372-379. doi: 10.1097/HJH.0000000000001854.

  PMID: 29995701 RESULT

• Lakatos LB, Bolognese M, Oesterreich M, Muller M, Karwacki GM. Cerebrovascular regulation in patients with active tumors and an acute ischemic stroke: a retrospective analysis. Front Physiol. 2024 Dec 19;15:1423195. doi: 10.3389/fphys.2024.1423195. eCollection 2024.

  PMID: 39749040 DERIVED

• Bolognese M, Weichsel L, Osterreich M, Muller M, Karwacki GM, Lakatos LB. Association of high-sensitivity cardiac troponin T with territorial middle cerebral artery brain infarctions and dynamic cerebral autoregulation. J Cent Nerv Syst Dis. 2024 Nov 25;16:11795735241302725. doi: 10.1177/11795735241302725. eCollection 2024.

  PMID: 39600968 DERIVED

• Lakatos LB, Shin DC, Muller M, Osterreich M, Marmarelis V, Bolognese M. Impaired dynamic cerebral autoregulation measured in the middle cerebral artery in patients with vertebrobasilar ischemia is associated with autonomic failure. J Stroke Cerebrovasc Dis. 2024 Jan;33(1):107454. doi: 10.1016/j.jstrokecerebrovasdis.2023.107454. Epub 2023 Nov 4.

  PMID: 37931481 DERIVED

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Martin Müller, MD

  Luzerner Kantonsspital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Müller, MD

CONTACT

+41 41 205; martin.mueller@luks.ch

Lehel Lakatos, MD

CONTACT

+41 41 205; Lehel-Barna.Lakatos@luks.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Dr med

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: November 2, 2020
• Study Start: October 11, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2025
• Last Updated: August 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 2021 - 2025
• Access Criteria: on request to M Müller

Locations

CH (1)