Noninvasive CA Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage

NCT07577739 | Not Yet Recruiting

• 1 other identifier: STU20260829
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Delayed Cerebral Ischemia; Cerebral Vasospasm; Autonomic Nervous System Diseases

Keywords

aneurysmal subarachnoid hemorrhage; delayed cerebral ischemia; cerebral autoregulation; CPPopt; MAPopt; pressure reactivity index; Brain4Care; cervical sympathetic block; stellate ganglion block; transcutaneous auricular vagal nerve stimulation; taVNS; autonomic modulation; EVD clamping; external ventricular drain; near-infrared spectroscopy; noninvasive ICP monitoring; neurocritical care

Outcome Measures

Primary Outcomes (6)

• Bland-Altman agreement between Brain4Care-derived noninvasive pressure reactivity index (nPRx) and invasive ICP-derived PRx during EVD clamping (Aim 1a)

  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)

  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)

  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)

  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)

  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)

  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

Secondary Outcomes (5)

• Proportion of monitoring sessions with computable NIRS-derived optimal mean arterial pressure (MAPopt)

  Through ICU Day 14

• Bland-Altman agreement between NIRS-derived and Brain4Care-derived optimal mean arterial pressure (MAPopt)

  Through ICU Day 14

• Incidence and severity of adverse events (CTCAE grade) related to cervical sympathetic block and taVNS procedures

  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

  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

  90 days post-hospital discharge

Study Arms (2)

Component 1: CA Monitoring and EVD Clamping Validation

NO INTERVENTION

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.

Component 2: Autonomic Modulation (CSB and taVNS)

EXPERIMENTAL

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.

Procedure: Right-Sided Cervical Sympathetic Block at C6; Device: Transcutaneous Auricular Vagal Nerve Stimulation (taVNS)

Interventions

Right-Sided Cervical Sympathetic Block at C6 PROCEDURE

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.

Also known as: Stellate Ganglion Block, Cervical Sympatholysis

Component 2: Autonomic Modulation (CSB and taVNS)

Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) DEVICE

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.

Also known as: Auricular Vagus Nerve Stimulation, TENS 7000

Component 2: Autonomic Modulation (CSB and taVNS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center - Clements University Hospital NSICU

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial; Autonomic Nervous System Diseases

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Noah Jouett, DO, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noah Jouett, DO, PhD

CONTACT

2147862783; Noah.Jouett@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Department of Anesthesiology and Pain Management

Model Details: Two-component sequential design. All participants enroll in Component 1 (observational CA monitoring and EVD clamping validation; no intervention). Component 2 (CSB and taVNS) is added to eligible Component 1 participants upon PI declaration of operational readiness. Within-subject before-after design for Component 2 intervention assessment.

Study Record Dates

• First Submitted: April 18, 2026
• First Posted: May 11, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 11, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)