Beta-sitosterol for Subarachnoid Hemorrhage: Mechanistic Analysis of Recovery and Therapy (B-SMART)

Subarachnoid Hemorrhage (SAH), a devastating form of stroke, is associated with high mortality and disability rates due to complex secondary brain injuries-including neuroinflammation, oxidative stress, and blood-brain barrier disruption-for which effective neuroprotective treatments remain scarce. Inspired by the neuroprotective properties of the traditional Chinese herb Gastrodia elata, this study identifies a novel bioactive mechanism: its extracellular vesicles (G-EVs) are naturally enriched with β-Sitosterol, a plant sterol with proven anti-inflammatory, antioxidant, and endothelial-protective effects.

This project represents the first clinical investigation into the therapeutic potential of β-Sitosterol for patients with aneurysmal SAH. Given the excellent safety profile of β-Sitosterol as a widely used dietary supplement, this study aims to evaluate its safety and tolerability in SAH patients while preliminarily exploring its efficacy in improving neurological outcomes. By analyzing key biomarkers of inflammation and oxidative stress, this research seeks to bridge the gap between traditional medicine and modern nanomedicine, offering a novel, safe, and accessible adjunct therapy for SAH and paving the way for plant-derived compounds in acute neurocritical care.

Study Overview

• Status: Enrolling by invitation
• Conditions: Subarachnoid Haemorrhagic Stroke
• Intervention / Treatment: Other: Standard medical treatment; Drug: Supplementation of β -sitosterol

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • 2ndAffiliated Hospital, School of Medicine, Zhejiang Universit

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 to 75 years, regardless of gender.
• Confirmed diagnosis of spontaneous aneurysmal subarachnoid hemorrhage (aSAH) by head CT or cerebral angiography (DSA/CTA).
• Time from symptom onset to planned first dose administration within 48 hours.
• Aneurysm successfully secured by surgical clipping or endovascular intervention.
• World Federation of Neurosurgical Societies (WFNS) grade I-III.
• Written informed consent signed by the patient or their legal representative.

Exclusion Criteria:

• Non-aneurysmal SAH (e.g., caused by trauma, arteriovenous malformation, etc.).
• Secondary to other severe intracranial diseases (e.g., large intracerebral hematoma, severe brain herniation).
• Complicated with severe cardiac, hepatic, renal, or hematopoietic system dysfunction (as defined by specific laboratory criteria).
• Known allergy to Gastrodia elata or any of its components.
• Pregnancy or breastfeeding.
• Participation in another interventional clinical trial within 30 days prior to enrollment.
• Any other condition that, in the judgment of the investigator, makes the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Standard treatment	Other: Standard medical treatment; Standard medical treatment
Experimental: Experimental Group; Standard treatment + sitosterol treatment	Other: Standard medical treatment; Standard medical treatment; Drug: Supplementation of β -sitosterol; Participants in the experimental arm will receive Nutricost β-Sitosterol Softgels. The total daily dose is 500 mg of β-Sitosterol, administered orally in two divided doses (e.g., 250 mg twice daily). The treatment will continue for a duration of 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the modified Rankin Scale (mRS) score	Functional independence measured by the modified Rankin Scale (mRS) score. A favorable outcome is typically defined as mRS score 0-2.	From baseline through the 6-month follow-up period (with intensive monitoring during the first 14 days).
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), with specific focus on allergic reactions, liver function (ALT/AST), renal function (Cr/BUN), and coagulation parameters (PT/APTT).	At 90 days (±7 days) post-treatment initiation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Levels of Inflammatory Cytokines	Dynamic changes in serum levels of inflammatory cytokines (e.g., TNF-α, IL-1β) and neuroprotective factors.	At baseline, 1 month, 3 months, and 6 months.
Glasgow Outcome Scale Extended (GOS-E) score	Glasgow Outcome Scale Extended (GOS-E) score to assess global disability and recovery, with scores ranging from 1 to 8 and higher scores indicating better outcomes.	At 1 month, 3 months (±7 days), and 6 months (±14 days).
Montreal Cognitive Assessment (MoCA) score	Montreal Cognitive Assessment (MoCA) score to evaluate cognitive impairment, with scores ranging from 0 to 30 and higher scores indicating better cognitive function.	At baseline (enrollment), 1 month, 3 months, and 6 months.
Short Form Health Survey (SF-36) score	Short Form Health Survey (SF-36) score to assess health-related quality of life, with scores for each domain ranging from 0 to 100 and higher scores indicating better health status.	At 90 days (±7 days) and 180 days (±14 days).
Radiological Outcomes Assessed by MRI (Cerebral Infarction, Edema)	Incidence of Delayed Cerebral Ischemia (DCI) and other neurological worsening events during the acute phase, diagnosed by imaging findings. Radiological assessments will be performed using computed tomography (CT) or magnetic resonance imaging (MRI) to evaluate: 1) Resolution of subarachnoid hemorrhage, measured by the Subarachnoid Hemorrhage Resolution Scale; 2) Incidence of cerebral infarction; 3) Incidence and severity of cerebral edema; and 4) Changes in meningeal lymphatic drainage function, measured by Dynamic Contrast-Enhanced MRI parameters.	At baseline, 1 month, 3 months, and 6 months.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Director: Yan Chen, 2ndAffiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2026-0151

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: No