Noninvasive CA Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Texas Southwestern Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

Age younger than 18 years

Prisoner status

Primary NSICU admission diagnosis other than aSAH

Active declination by subject or legally authorized representative

Trial design

Design model

Sequential

Treatments tested in this trial

  • Right-Sided Cervical Sympathetic Block at C6

    Procedure/Surgery

    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.

  • 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.

Treatment groups

300 Participants
are divided into 2 treatment groups
Group A: Component 1: CA Monitoring and EVD Clamping ValidationNo intervention 0 interventions
Group B: Component 2: Autonomic Modulation (CSB and taVNS)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
During each standardized 15-minute EVD clamping session, up to one session per 24-hour period over ICU Days 1-14
2

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.

Time frame
During each standardized 15-minute EVD clamping session, up to one session per 24-hour period over ICU Days 1-14
3

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.

Time frame
ICU admission through Day 14 post-rupture
4

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.

Time frame
ICU admission through Day 14 post-rupture

Secondary outcomes

1

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

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.

Time frame
Through ICU Day 14
2

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

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.

Time frame
Through ICU Day 14
3

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

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.

Time frame
During and up to 24 hours after each intervention session
4

Change in root mean square of successive R-R interval differences (RMSSD) from continuous ECG before versus after autonomic modulation

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.

Time frame
60 minutes before through 60 minutes after each Component 2 intervention session

Other outcomes

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