Stroke, AcuteNCT04611672
Linearity and Non-linearity of Cerebral Autoregulation
An observational study of Stroke, Acute, run by Luzerner Kantonsspital at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Stroke, Acute
- What is being tested?
- Assessment of CA and Assesment of CA only
- Type of treatment
- Injection or infusion
- How many people
- 580 participants
- Where
- 1 siteSwitzerland
- Study dates
- 11 Oct 2020to 31 Dec 2025
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 110 years
- All sexes
- Adult, Older adult
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
Who may be able to join
- every typ of ischemic stroke of any severity
- presence of a "temporal bone window"
Who cannot join
- Age < 18 years,
- pregnancy
- no informed consent.
- absence of a "temporal bone window"
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Kantonsspital Luzern
Lucerne, 6000
Martin Müller, MD, +41 41 205 ext. 5133, martin.mueller@luks.ch
Lehel Lakatos, MD, +41 41 205 ext. 6266, Lehel-Barna.Lakatos@luks.ch
About this study
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 ?
Read the 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
- Conditions
- Stroke, Acute
- Being tested
- Assessment of CA, Assesment of CA only
- Keywords
- Stroke, Cerebral autoregulation, Doppler, Carotid disease
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Assessment of CADiagnostic 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
Assesment of CA onlyDiagnostic test
Assessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates
| Study group | Role | What they receive |
|---|---|---|
| Patients with stroke | Patients with stroke of all subtypes, with and without different Kind of Lysis therapy Receives: Diagnostic Test: Assessment of CA | |
| Controls | Healthy controls of all Ages above 18 years Receives: Diagnostic Test: Assesment of CA only |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Assessment on days 1-3 after stroke onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2020
- Study start11 Oct 2020
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 580 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- Luzerner Kantonsspital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Martin Müller, Luzerner Kantonsspital
- Investigators
- Martin Müller, MD, Principal investigator, Luzerner Kantonsspital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04611672
- Sponsor's protocol ID
- PB_2016-01719
- Status last verified
- Aug 2022
- First submitted
- 21 Oct 2020
- Last updated
- 26 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 32090712Meel-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.
PubMed 24725709Claassen 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.
PubMed 26782760Muller 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.
PubMed 32514031Muller 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.
PubMed 29995701Lakatos 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.
PubMed 39749040Bolognese 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.
PubMed 39600968Lakatos 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.
PubMed 37931481
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Linearity and Non-linearity of Cerebral Autoregulation
- ClinicalTrials.gov ID
- NCT04611672
- Acronym / sponsor ID
- PB_2016-01719
- Conditions
- Stroke, Acute
- Keywords
- Stroke, Cerebral autoregulation, Doppler, Carotid disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 580 participants (estimated)
- Lead sponsor
- Luzerner KantonsspitalUniversity, hospital or other
- Study start
- 11 Oct 2020 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 2 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 ?
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with stroke | – | Diagnostic Test: Assessment of CAPatients with stroke of all subtypes, with and without different Kind of Lysis therapy |
| Controls | – | Diagnostic Test: Assesment of CA onlyHealthy controls of all Ages above 18 years |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (2 listed)
- every typ of ischemic stroke of any severity
- presence of a "temporal bone window"
Key exclusion criteria (4 listed)
- Age < 18 years,
- pregnancy
- no informed consent.
- absence of a "temporal bone window"
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Assessment of CAAs 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 | Diagnostic test | Patients with stroke |
| Assesment of CA onlyAssessing CA by continuous recording of blood pressure, cerebral blood flow velocity, end-tidal CO2. Analysis via Transfer function estimates | Diagnostic test | Controls |
Primary outcome
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
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2022.
- Background: PubMed 32090712Beishon 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.
- Background: PubMed 24725709Meel-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.
- Background: PubMed 26782760Claassen 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.
- Results publication: PubMed 32514031Muller 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.
- Results publication: PubMed 29995701Muller 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.
- Derived from this study: PubMed 39749040Lakatos 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.
- Derived from this study: PubMed 39600968Bolognese 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.
- Derived from this study: PubMed 37931481Lakatos 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.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Müller, MD principal investigator
Luzerner Kantonsspital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stroke, Acute, run by Luzerner Kantonsspital at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martin Müller, MD (+41 41 205 ext. 5113, martin.mueller@luks.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04611672, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2022.