Effectiveness and Biological Mechanism of Direct Ischemic Post-conditioning for Acute Stroke Patients Due to Large Vessel Occlusion

Effectiveness and Biological Mechanism of Direct Ischemic Post-conditioning for Acute Stroke Patients Due to Large Vessel Occlusion: A Randomized Controlled Pilot Trial

The goal of this clinical trial is to determine if direct ischemic post-conditioning (IPostC) can alleviate ischemic-reperfusion injury (I/R) in patients who have undergone endovascular thrombectomy (EVT). Additionally, the study aims to explore the underlying mechanisms of direct IPostC.

The primary questions this trial seeks to answer are:

1. Is direct IPostC effective for acute stroke patients with large vessel occlusion?
2. What are the underlying mechanisms of direct IPostC?

Participants will be randomly assigned to one of two groups: an EVT alone group or an EVT plus direct IPostC group. Direct IPostC will be administered immediately after EVT through four cycles of mechanical interruptions of reperfusion. We will evaluate outcomes based on final infarct volume, infarct volume growth, clinical parameters, and I/R-related imaging and laboratory biomarkers. Additionally, an exploratory multi-omics analysis will be conducted to uncover the detailed mechanisms of direct IPostC.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute; Neuroprotection; Ischemic Conditioning
• Intervention / Treatment: Procedure: Endovascular therapy; Procedure: Direct Ischemic Post-conditioning

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Wei, MD, PhD; Phone Number: 13502182903; Email: drweiming@163.com
• Study Contact Backup: Name: Yongbo Xu, MD; Phone Number: 17361616533; Email: yonbur@outlook.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300070
      • Recruiting
      • Tianjin Huanhu Hospital
      • Contact: Ming Wei, MD, PhD; Phone Number: 13502182903; Email: drweiming@163.com
      • Principal Investigator: Ming Wei, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Ischemic stroke confirmed by CT or MRI.
2. Large vessel occlusion confirmed by CTA or MRA, including the intracranial internal 3. carotid artery (ICA) and middle cerebral artery (MCA M1/M2).

4. Recanalization of the occluded vessel at eTICI grade 2b/3, confirmed by DSA after thrombectomy.

5. The patient or legally authorized representative has signed an informed consent form.

Exclusion Criteria:

1. Inability to perform an MRI or CT scan for any reason.
2. Presence of any condition that would interfere with neurological assessment or any psychiatric disorders.
3. Stroke onset accompanied by seizures, resulting in the inability to obtain an accurate NIHSS baseline.
4. Pregnancy.
5. Presence of other serious, advanced, or terminal illnesses.

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
Active Comparator: Endovascular therapy	Procedure: Endovascular therapy; Thrombectomy alone.
Experimental: Endovascular therapy plus direct ischemic post-conditioning	Procedure: Endovascular therapy; Thrombectomy alone.; Procedure: Direct Ischemic Post-conditioning; After thrombectomy, the balloon was inflated to a pressure of no more than 4 atm at the occlusion site to block blood flow for 2 minutes, as confirmed by angiography. The balloon was then deflated, allowing blood flow to resume for 2 minutes. These steps were repeated four times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Final Infarct volume	Infarct volume at 24 (-6/+12) hours postoperatively	24(-6/+12) hours after procedure
Infarct Volume Growth	Infarct volume at 24 (-6/+12) hours - Infarct volume at baseline; Infarct volume at 24 (-6/+12) hours - Infarct volume at 2 hours	24(-6/+12) hours after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NIHSS between baseline and 2 hours	NIHSS at 2 hours - NIHSS at baseline	2 hours after procedure
Change in NIHSS between baseline and 24 hours	NIHSS at 24 hours - NIHSS at baseline	24 hours after procedure
Functional Independence at 90 days	The proportion of mRS 0-2 at 90 days	90 days after randomization
Functional Independence at 5 days or discharge	The proportion of mRS 0-2 at 5 days or discharge	5 days or at discharge after randomization
Blood brain barrier permeability at 72 hours	This is quantified by ktrans value through MR	72 hours after procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Peripheral circulating immune cells counts	Immune cell counts acquired from CBC.	1, 3 and 5 days after procedure
Difference in lymphocyte phenotyping	CD4 T cells, CD8 T cells, B cells, NK cells count by flow cytometry.	PBMC isolated from peripheral venous blood at 24 hours
Difference in expression of genes associated with T cell polarization	TBX21, GATA3, RORC and FOXP3	PBMC isolated from peripheral venous blood at 24 hours
Difference in cytokines and chemokines associated with T cell polarization and recruitment	IL-1β, IL-18, IL-17, IL-10, IFN-γ, TNF-α, IL-6, CX3CL1, CXCL10, CCL17	Serum isolated from peripheral venous blood at 24 hours

Collaborators and Investigators

• Sponsor: Tianjin Huanhu Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Stroke, Acute; Large Vessel Occlusion; Neuroprotection
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemia
• Other Study ID Numbers: TJHH-2024-WM28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No