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Noninvasive CA Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage

4 de maio de 2026 atualizado por: Noah Jouett, University of Texas Southwestern Medical Center

Non-Invasive Cerebral Autoregulation Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage: A Two-Component Prospective Study of EVD Clamping Validation, CA Natural History, and the Effects of Cervical Sympathetic Block and Transcutaneous Auricular Vagal Nerve Stimulation on Cerebral Autoregulation Parameters

This is a two-component prospective study of adult aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to the Neurosciences Intensive Care Unit (NSICU) at UT Southwestern Medical Center. Component 1 (active upon IRB approval) validates Brain4Care (B4C) extensometry-derived noninvasive cerebral autoregulation (CA) indices against invasive ICP-derived equivalents in aSAH patients with open external ventricular drains (EVDs), and characterizes the prospective natural history of multi-modal CA parameter evolution through the delayed cerebral ischemia (DCI) window (admission through Day 14). Component 2 (activated upon PI readiness declaration) assesses the within-subject effect of cervical sympathetic block (CSB) and transcutaneous auricular vagal nerve stimulation (taVNS) on CA parameters in enrolled aSAH patients.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) affects approximately 35,000 Americans annually and carries a 30-day mortality of approximately 40%. Delayed cerebral ischemia (DCI) - caused by vasospasm, microvascular dysfunction, and impaired cerebrovascular regulation - complicates 25-35% of survivors during the 4-14 day post-rupture window. Cerebral autoregulation (CA) impairment predicts DCI onset and poor neurological outcome. Standard ICP-based CA indices cannot be computed through an open EVD - present in approximately 50-75% of aSAH patients - because the transducer is exposed to ambient pressure. This technical barrier has precluded CA-guided management in the most common clinical aSAH scenario for over two decades.

The autonomic nervous system is a central, understudied regulator of CA in aSAH. Aneurysm rupture produces a massive catecholamine surge coinciding with the early window of CA impairment. We hypothesize that sympathetically-mediated cerebrovascular vasoconstriction contributes to CA failure, and that restoration of sympathovagal balance can shift CA parameters toward a more protective state.

TWO-COMPONENT DESIGN:

COMPONENT 1 - Validation and Natural History (activates immediately upon IRB approval):

A standardized 15-minute EVD clamping protocol (5-minute equilibration plus 10-minute simultaneous invasive/noninvasive CA recording; ICP abort threshold greater than 20 mmHg sustained for 5 or more minutes) is used to validate B4C-derived CA indices (nPRx, nCPPopt, nMx) against invasive ICP-derived equivalents by Bland-Altman analysis and intraclass correlation. NIRS-based MAPopt (TOxA, COx) is characterized as an EVD-independent CA metric. Longitudinal multi-modal CA monitoring proceeds through ICU Day 14 for all enrolled participants.

COMPONENT 2 - Autonomic Modulation (PI readiness-gated):

Within-subject before-after assessment of right-sided cervical sympathetic block (CSB; ultrasound-guided, C6 approach, low-volume ropivacaine) and transcutaneous auricular vagal nerve stimulation (taVNS; 25 Hz, 200-500 microamps, 200 microsecond pulse width via TENS 7000 to cymba conchae; 20-minute sessions twice daily for up to 14 days) on CPPopt, MAPopt, Mx, and CPPopt-MAP deviation. Activation requires documented PI readiness attestation co-signed by a qualified co-investigator or Department Director.

SAFETY (Component 2):

CSB: Continuous cardiac monitoring; pre-procedure coagulation screening (INR 1.5 or less, platelets 50,000/uL or greater within 24 hours); real-time ultrasound guidance. Expected transient ipsilateral Horner syndrome lasting 2-6 hours. Serious adverse event rate less than 0.1% with low-volume technique.

taVNS: Continuous cardiac telemetry; immediate device removal for HR below 50 bpm. Parameters consistent with NAVSaH trial and published taVNS literature.

SIGNIFICANCE: Each aim is independently executable and generates independently publishable results. A positive Component 2 result directly motivates an NIH R01 for a powered randomized trial. A null result establishes the first causal evidence regarding non-modifiability of CPPopt by autonomic intervention, reorienting the field. The study cannot produce a non-informative result.

Tipo de estudo

Intervencional

Inscrição (Estimado)

300

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Estados Unidos
    • Texas
      • Dallas, Texas, Estados Unidos, 75390
        • UT Southwestern Medical Center - Clements University Hospital NSICU
        • Investigador principal:
          • Noah Jouett, DO, PhD
        • Contato:
        • Subinvestigador:
          • Ulrike Hoffmann, MD, PhD
        • Subinvestigador:
          • DaiWai Olson, PhD, RN

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria (Component 1 - All Enrolled Participants):

  • Age 18 years or older
  • Primary diagnosis of aneurysmal subarachnoid hemorrhage (aSAH), confirmed by imaging
  • Admitted to the NSICU at Clements University Hospital, UT Southwestern Medical Center
  • Informed consent obtained from subject or legally authorized representative (as defined under Texas Health and Safety Code Section 166.039)
  • Brain4Care extensometry sensor placeable at an appropriate cranial site not occluded by surgical dressings or EVD hardware
  • Open EVD with active continuous ICP monitoring (required for EVD clamping sub-protocol only; not required for Aims 2 or 3)

Exclusion Criteria (Component 1):

  • Age younger than 18 years
  • Prisoner status
  • Primary NSICU admission diagnosis other than aSAH
  • Active declination by subject or legally authorized representative
  • Brain4Care sensor not placeable at any accessible cranial site
  • Active clinical deterioration making research monitoring impractical at time of approach
  • Physician-of-record declining research enrollment for clinical reasons
  • Inability to provide informed consent in English
  • Known pregnancy at time of enrollment

Additional Inclusion Criteria for Component 2 (Aim 3 - CSB and taVNS):

  • At least one successful EVD clamping session completed
  • PI documentation of Component 2 operational readiness, co-signed by qualified co-investigator or Department Director
  • INR 1.5 or less and platelet count 50,000/uL or greater within 24 hours prior to each CSB procedure
  • No active infection or cellulitis at right anterolateral neck
  • No known allergy to ropivacaine or amide local anesthetics
  • No contralateral phrenic nerve palsy or severe pre-existing respiratory compromise
  • No cardiac pacemaker or implanted cardiac device contraindicating taVNS
  • No allergy to electrode adhesive materials
  • Continuous cardiac telemetry active and interpretable
  • Resting HR 60 bpm or greater on two readings within 24 hours prior to session
  • No current use of Class I or III antiarrhythmic medications
  • No clinically significant AV conduction abnormality

Additional Exclusion Criteria for Component 2:

  • Prior ipsilateral right-sided cervical surgery, radiation, or known anatomical distortion precluding safe C6 approach
  • Hemodynamic instability with active vasopressor escalation at time of planned CSB
  • Active uncontrolled tachyarrhythmia or bradyarrhythmia at time of taVNS session
  • Physician-of-record declining autonomic modulation procedures for any clinical reason
  • Known or suspected pregnancy

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Ciência básica
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição sequencial
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Sem intervenção: Component 1: CA Monitoring and EVD Clamping Validation
All enrolled aSAH patients. Multimodal CA monitoring (B4C extensometry, NIRS-derived indices, invasive ICP/CPP from EVD where present) throughout ICU Days 1-14. Participants with open EVDs additionally undergo a standardized 15-minute EVD clamping sub-protocol for simultaneous invasive/noninvasive CA index validation, up to one session per 24-hour period. No interventional procedures administered under Component 1.
Experimental: Component 2: Autonomic Modulation (CSB and taVNS)
Component 1 participants meeting Component 2 eligibility criteria after PI readiness declaration. Receive right-sided cervical sympathetic block (CSB; ultrasound-guided, C6) and transcutaneous auricular vagal nerve stimulation (taVNS; cymba conchae, TENS 7000; twice daily 20-minute sessions for up to 14 days). Within-subject before-after assessment of CA parameter effects. CA monitoring from Component 1 continues throughout.
Procedimento: Right-Sided Cervical Sympathetic Block at C6
Ultrasound-guided right-sided cervical sympathetic block targeting pre-ganglionic cervical sympathetic fibers at the C6 level using low-volume ropivacaine. Real-time ultrasound guidance with aspiration prior to injection. Continuous cardiac monitoring throughout. Coagulation parameters confirmed within 24 hours of each procedure. Expected transient ipsilateral Horner syndrome lasting 2-6 hours.
Outros nomes:
  • Bloco do Gânglio Estrelado
  • Cervical Sympatholysis
Dispositivo: Transcutaneous Auricular Vagal Nerve Stimulation (taVNS)
Noninvasive vagal augmentation delivered via electrode placed at the cymba conchae of the right ear using the TENS 7000 device. Parameters: 25 Hz, 200-500 microamps, 200 microsecond pulse width; 20-minute sessions twice daily for up to 14 days (maximum 28 sessions). Continuous cardiac telemetry required; immediate device removal if HR falls below 50 bpm. Intensity set below pain threshold based on participant comfort feedback.
Outros nomes:
  • Estimulação nervosa vaga auricular
  • TENS 7000

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Bland-Altman agreement between Brain4Care-derived noninvasive pressure reactivity index (nPRx) and invasive ICP-derived PRx during EVD clamping (Aim 1a)
Prazo: During each standardized 15-minute EVD clamping session, up to one session per 24-hour period over ICU Days 1-14
Bland-Altman limits of agreement and intraclass correlation coefficient between Brain4Care (B4C)-derived noninvasive pressure reactivity index (nPRx; unitless, range -1 to +1) and simultaneously acquired invasive ICP-derived PRx during standardized 15-minute EVD clamping sessions. Sessions aborted if ICP exceeds 20 mmHg sustained for 5 or more minutes. Target: 30-50 clamping sessions for Bland-Altman precision.
During each standardized 15-minute EVD clamping session, up to one session per 24-hour period over ICU Days 1-14
Bland-Altman agreement between Brain4Care-derived noninvasive optimal cerebral perfusion pressure (nCPPopt) and invasive ICP-derived CPPopt during EVD clamping (Aim 1b)
Prazo: During each standardized 15-minute EVD clamping session, up to one session per 24-hour period over ICU Days 1-14
Bland-Altman limits of agreement and intraclass correlation coefficient between Brain4Care (B4C)-derived noninvasive optimal cerebral perfusion pressure (nCPPopt; reported in mmHg) and simultaneously acquired invasive ICP-derived CPPopt during standardized 15-minute EVD clamping sessions. Sessions aborted if ICP exceeds 20 mmHg sustained for 5 or more minutes. Target: 30-50 clamping sessions for Bland-Altman precision.
During each standardized 15-minute EVD clamping session, up to one session per 24-hour period over ICU Days 1-14
Invasive ICP-derived optimal cerebral perfusion pressure (CPPopt) trajectory through the DCI window in aSAH (Aim 2a)
Prazo: ICU admission through Day 14 post-rupture
Prospective characterization of invasive ICP-derived optimal cerebral perfusion pressure (CPPopt; reported in mmHg) trajectory from ICU admission through Day 14 in aSAH patients. Temporal correlation of CPPopt trajectory with DCI onset (clinical and imaging-confirmed) and neurological outcome at discharge, reported as Spearman correlation coefficients.
ICU admission through Day 14 post-rupture
NIRS-derived cerebral oximetry index (COx) trajectory through the DCI window in aSAH (Aim 2b)
Prazo: ICU admission through Day 14 post-rupture
Prospective characterization of near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx; unitless, range -1 to +1) trajectory from ICU admission through Day 14 in aSAH patients. Temporal correlation of COx trajectory with DCI onset (clinical and imaging-confirmed) and neurological outcome at discharge, reported as Spearman correlation coefficients.
ICU admission through Day 14 post-rupture
Change in invasive ICP-derived optimal cerebral perfusion pressure (CPPopt) before versus after cervical sympathetic block and taVNS (Aim 3a)
Prazo: 60 minutes before through 60 minutes after each intervention session
Within-subject paired change in invasive ICP-derived optimal cerebral perfusion pressure (CPPopt; reported in mmHg) comparing a 60-minute pre-intervention monitoring epoch with a 60-minute post-intervention monitoring epoch. Assessed separately for CSB and taVNS. Target: 20-30 paired sessions per intervention for 80% power to detect a shift of 5 mmHg or greater at alpha=0.05 two-sided.
60 minutes before through 60 minutes after each intervention session
Change in NIRS-derived optimal mean arterial pressure (MAPopt) before versus after cervical sympathetic block and taVNS (Aim 3b)
Prazo: 60 minutes before through 60 minutes after each intervention session
Within-subject paired change in near-infrared spectroscopy (NIRS)-derived optimal mean arterial pressure (MAPopt; reported in mmHg) comparing a 60-minute pre-intervention monitoring epoch with a 60-minute post-intervention monitoring epoch. Assessed separately for CSB and taVNS. Target: 20-30 paired sessions per intervention for 80% power to detect a shift of 5 mmHg or greater at alpha=0.05 two-sided.
60 minutes before through 60 minutes after each intervention session

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Proportion of monitoring sessions with computable NIRS-derived optimal mean arterial pressure (MAPopt)
Prazo: Through ICU Day 14
Percentage of monitoring sessions with computable near-infrared spectroscopy (NIRS)-derived optimal mean arterial pressure (MAPopt), reported as a single proportion. Characterization across EVD-present and EVD-absent aSAH subgroups.
Through ICU Day 14
Bland-Altman agreement between NIRS-derived and Brain4Care-derived optimal mean arterial pressure (MAPopt)
Prazo: Through ICU Day 14
Bland-Altman limits of agreement (reported in mmHg) between near-infrared spectroscopy (NIRS)-derived optimal mean arterial pressure (MAPopt) and Brain4Care (B4C) extensometry-derived MAPopt. Characterization across EVD-present and EVD-absent aSAH subgroups.
Through ICU Day 14
Incidence and severity of adverse events (CTCAE grade) related to cervical sympathetic block and taVNS procedures
Prazo: During and up to 24 hours after each intervention session
Incidence and characterization of adverse events attributable to CSB (Horner syndrome duration and resolution, local anesthetic systemic toxicity, hematoma, hoarseness, hemodynamic effects) and taVNS (bradycardia, auricular skin irritation, stimulation discomfort). All events classified by Common Terminology Criteria for Adverse Events (CTCAE) grade and reported as incidence per intervention session.
During and up to 24 hours after each intervention session
Change in root mean square of successive R-R interval differences (RMSSD) from continuous ECG before versus after autonomic modulation
Prazo: 60 minutes before through 60 minutes after each Component 2 intervention session
Within-subject paired change in RMSSD (reported in milliseconds) derived from continuous ECG monitoring, comparing 60-minute pre-intervention and 60-minute post-intervention epochs for each CSB and taVNS session. RMSSD serves as the primary heart rate variability metric reflecting parasympathetic (vagal) tone. Additional HRV indices (SDNN, LF/HF ratio) reported descriptively as secondary exploratory analyses using the same pre-post epoch comparison.
60 minutes before through 60 minutes after each Component 2 intervention session
Functional status at 90 days assessed by modified Rankin Scale via medical record review
Prazo: 90 days post-hospital discharge
Functional and neurological status assessed by modified Rankin Scale (mRS) score via medical record review and/or structured contact at 90 days. Reported as ordinal mRS score (0-6). Correlation with CA index features during the DCI window reported as Spearman correlation coefficients.
90 days post-hospital discharge

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

University of Texas Southwestern Medical Center

Investigadores

  • Investigador principal: Noah Jouett, DO, PhD, University of Texas Southwestern Medical Center

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de julho de 2026

Conclusão Primária (Estimado)

1 de junho de 2029

Conclusão do estudo (Estimado)

1 de junho de 2030

Datas de inscrição no estudo

Enviado pela primeira vez

18 de abril de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

4 de maio de 2026

Primeira postagem (Real)

11 de maio de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

11 de maio de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

4 de maio de 2026

Última verificação

1 de abril de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • STU20260829

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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