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Noninvasive CA Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage

2026년 5월 4일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

300

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

  • 미국
    • Texas
      • Dallas, Texas, 미국, 75390
        • UT Southwestern Medical Center - Clements University Hospital NSICU
        • 수석 연구원:
          • Noah Jouett, DO, PhD
        • 연락하다:
        • 부수사관:
          • Ulrike Hoffmann, MD, PhD
        • 부수사관:
          • DaiWai Olson, PhD, RN

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 기초 과학
  • 할당: 무작위화되지 않음
  • 중재 모델: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
간섭 없음: 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.
실험적: 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.
절차: 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.
다른 이름들:
  • 별 모양의 신경절 블록
  • Cervical Sympatholysis
장치: 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.
다른 이름들:
  • 귀의 미주 신경 자극
  • TENS 7000

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Bland-Altman agreement between Brain4Care-derived noninvasive pressure reactivity index (nPRx) and invasive ICP-derived PRx during EVD clamping (Aim 1a)
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Proportion of monitoring sessions with computable NIRS-derived optimal mean arterial pressure (MAPopt)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

University of Texas Southwestern Medical Center

수사관

  • 수석 연구원: Noah Jouett, DO, PhD, University of Texas Southwestern Medical Center

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 7월 1일

기본 완료 (추정된)

2029년 6월 1일

연구 완료 (추정된)

2030년 6월 1일

연구 등록 날짜

최초 제출

2026년 4월 18일

QC 기준을 충족하는 최초 제출

2026년 5월 4일

처음 게시됨 (실제)

2026년 5월 11일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 5월 11일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 5월 4일

마지막으로 확인됨

2026년 4월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • STU20260829

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다