The Effect of Sympathetic Modulation on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage

The purpose of the study is to see that in addition to existing therapy, how well an additional procedure named spinal cord stimulation might reduce blood vessel spasm from aneurysm rupture.

Study Overview

• Status: Not yet recruiting
• Conditions: Aneurysmal Subarachnoid Hemorrhage; Vasospasm, Cerebral
• Intervention / Treatment: Device: Vectris trial leads and stimulation; Device: Sham

Detailed Description

The Investigators' overarching hypothesis is that sympathetic innervation plays a substantial role in conferring cerebral vasospasm (CVS) risk to aneurysmal subarachnoid hemorrhage (aSAH) patients and is associated with severity of clinical features and outcomes. Specifically, the Investigators surmise that central (hypothalamic) and local (arterial adventitia) sympathetic inputs are upregulated following SAH and integrate at the level of the neuromuscular junction to abnormally increase cerebrovascular tone. The long-term goal of this program is to use orthogonal approaches to undertake a comprehensive electrophysiological, functional genomics, and advanced imaging analysis of CVS. The Investigators hope is these data inform therapeutic pathways to modulate implicated pathogenic mechanisms and reduce CVS incidence and severity, thereby improving overall clinical outcomes in aSAH. In the short-term, the Investigators will focus on elucidating the modulatory role of cervical spinal cord stimulator (SCS) on sympathetic innervation to the cerebral vasculature.

This is a Phase 2 prospective, randomized single center study assessing the safety and efficacy of SCS for reducing vasospasm. aSAH patients who meet inclusion criteria and provide informed consent will be randomly assigned to SCS or a sham procedure. Subjects will be blinded until the end of the study, with no allowance for crossover. Temporary leads will stimulate, utilizing a paradigm established from prior human studies and the effect measured with daily transcranial doppler (TCD). Leveraging prior experience in vascular and functional neurosurgery, the Investigators' group is poised to make a substantial impact. Below the Investigators outline a feasible framework to modulate sympathetic drivers of CVS.

Aim 1: Perform feasibility analysis of SCS placement and operation in the aSAH setting. It is presently unknown how temporary SCS will impact the workflow and care of patients with acutely ruptured cerebral aneurysms. Given the rate of new aSAH cases at the Investigators' center (~50 per year), initiation of prospective data collection and longitudinal study are required. The Investigators will comprehensively assess operative time for electrode implantation, lead function and data transmission efficiency in the ICU, site infection/pressure injury and untoward systemic effects (hypotension, arrhythmia) for all patients enrolled at the Investigators' center.

Aim 2: Quantify the sympathetic modulating effect of SCS on cerebral blood flow during CVS. Further characterization of the sympathetic contribution to CVS will establish a rationale for functional/neuromodulatory therapies such as SCS. The Investigators will perform cervical epidural stimulation through temporary leads and monitor effects on cerebral blood flow by daily TCD. Experiments will continue throughout the 14-day CVS window to capture longitudinal changes in sympathetic tone and vascular response. Quantitative TCD metrics (velocity, resistance, Lindegaard ratio) will be compared between on- and off-stimulation epochs. The Investigators' study will not only fundamentally advance the Investigators' understanding of vasospasm, but also provide a framework to elucidate mechanisms of other cerebrovascular conditions.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jesse Jones, MD; Phone Number: 205-934-7170; Email: jessejones@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Diagnosed with Fisher grade 3 or 4 aneurysmal subarachnoid hemorrhage (1)
4. Ability to undergo endovascular treatment of aneurysmal subarachnoid hemorrhage
5. For females of reproductive potential: Negative pregnancy test at time of treatment
6. Plan to undergo standard of care and follow-up

Exclusion Criteria:

1. Medically unfit to undergo endovascular treatment (e.g., Hunt Hess grade 5)
2. Does not provide consent for the procedure.
3. Posterior circulation aneurysmal subarachnoid hemorrhage.
4. Initial aneurysm treatment after post bleed day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spinal Cord Stimulation; Participants randomized to receive temporary electrode inserted through the skin into the epidural space of participants upper back/lower neck.	Device: Vectris trial leads and stimulation; The electrode is placed into the epidural space using standard epidural placement techniques with paramedian approach. The initial electrode settings have been adopted from prior studies. Should any significant discomfort be elicited from the stimulation, first the amplitude will be decreased to an acceptable level. If an acceptable level of stimulation is unable to be found, the stimulation will be discontinued.
Sham Comparator: Sham Comparator; Participants randomized to not receive temporary electrode.	Device: Sham; No electrode is placed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-Cerebrovascular response - Velocity	Pre-SCS measures of cerebral blood flow. Subjects will serve as their own internal control (on vs off stimulation) and be grouped collectively to enable more robust statistical analysis. To study the effect of SCS on cerebrovascular tone longitudinally over the course of the vasospasm window, mixed model statistics will be applied.	Day 1 - Day 14
Pre-Cerebrovascular response - Resistance	Pre-SCS measures of cerebral blood flow. Subjects will serve as their own internal control (on vs off stimulation) and be grouped collectively to enable more robust statistical analysis. To study the effect of SCS on cerebrovascular tone longitudinally over the course of the vasospasm window, mixed model statistics will be applied.	Day 1 - Day 14
Pre-Cerebrovascular response - Lindegaard ratio	Pre-SCS measures of cerebral blood flow. Subjects will serve as their own internal control (on vs off stimulation) and be grouped collectively to enable more robust statistical analysis. To study the effect of SCS on cerebrovascular tone longitudinally over the course of the vasospasm window, mixed model statistics will be applied.	Day 1 - Day 14
Post-Cerebrovascular response - Velocity	Post SCS measures of cerebral blood flow. Subjects will serve as their own internal control (on vs off stimulation) and be grouped collectively to enable more robust statistical analysis. To study the effect of SCS on cerebrovascular tone longitudinally over the course of the vasospasm window, mixed model statistics will be applied.	Day 1 - Day 14
Post-Cerebrovascular response - Resistance	Post SCS measures of cerebral blood flow. Subjects will serve as their own internal control (on vs off stimulation) and be grouped collectively to enable more robust statistical analysis. To study the effect of SCS on cerebrovascular tone longitudinally over the course of the vasospasm window, mixed model statistics will be applied.	Day 1 - Day 14
Post-Cerebrovascular response - Lindegaard ratio	Post SCS measures of cerebral blood flow. Subjects will serve as their own internal control (on vs off stimulation) and be grouped collectively to enable more robust statistical analysis. To study the effect of SCS on cerebrovascular tone longitudinally over the course of the vasospasm window, mixed model statistics will be applied.	Day 1 - Day 14
Transcranial Doppler (TCD) velocities of cerebral arteries	Daily transcranial Doppler studies will be performed to obtain quantitative data on cerebrovascular response during the critical 14-day vasospasm window.	Day 1 - Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined for all patients and measured from time of treatment to death or end of a study. The analyses for overall survival will be like that of the primary endpoint. It will also utilize Kaplan Meier methods and Cox proportional hazards modeling to compare the overall survival to the treatment-dependent prognosis index.	Through study completion, approximately 24 months

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Jesse Jones, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 29, 2024
• First Posted (Actual): June 5, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: CVS; aSAH; Sympathetic Modulation; Ruptured brain aneurysm
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Vasospasm, Intracranial
• Other Study ID Numbers: IRB-300012920; UAB (Other Identifier: UAB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No