Subarachnoid Hemorrhage, AneurysmalNCT07577739
Noninvasive CA Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage
A study testing Right-Sided Cervical Sympathetic Block at C6 and Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) in people with Subarachnoid Hemorrhage, Aneurysmal and Delayed Cerebral Ischemia, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal, Delayed Cerebral Ischemia, Cerebral Vasospasm
- What is being tested?
- Right-Sided Cervical Sympathetic Block at C6 and Transcutaneous Auricular Vagal Nerve Stimulation (taVNS)
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2027to Jun 2030
- Phase
- Interventional
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
UT Southwestern Medical Center - Clements University Hospital NSICU
Dallas, Texas, 75390
Noah Jouett, DO, PhD, 2147862783, Noah.Jouett@UTSouthwestern.edu
Noah Jouett, DO, PhD
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal, Delayed Cerebral Ischemia, Cerebral Vasospasm, Autonomic Nervous System Diseases
- Being tested
- Right-Sided Cervical Sympathetic Block at C6, Transcutaneous Auricular Vagal Nerve Stimulation (taVNS)
- 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
- Medical subject headings
- Subarachnoid Hemorrhage, Vasospasm, Intracranial, Autonomic Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Right-Sided Cervical Sympathetic Block at C6Procedure or surgery
Also called Stellate Ganglion Block, Cervical Sympatholysis
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
Also called Auricular Vagus Nerve Stimulation, TENS 7000
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Right-Sided Cervical Sympathetic Block at C6; Device: Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: Through ICU Day 14
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.
Measured: Through ICU Day 14
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.
Measured: 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
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.
Measured: 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
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.
Measured: 90 days post-hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2026
- Study startJul 2027 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Noah Jouett, University of Texas Southwestern Medical Center
- Investigators
- Noah Jouett, DO, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07577739
- Sponsor's protocol ID
- STU20260829
- Status last verified
- Oct 2026
- First submitted
- 18 Apr 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No