Small Vessel Disease and Cerebral Infarct Healing InErvation Via Limb Distant Adaptation (SHIELD)

March 25, 2026 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

the Role and Mechanism of Distant Ischemic Adaptation in Improving Cognitive Impairment in Cerebral Infarction and Cerebral Small Vessel Disease

Cerebral infarction (ischemic stroke) and cerebral small vessel disease (CSVD) represent major global causes of disability, cognitive decline, and mortality. Despite advances in reperfusion therapies, many patients experience residual neurological deficits and remain at high risk for recurrent stroke and vascular dementia. Effective adjunctive treatments that are safe, accessible, and capable of improving long-term outcomes are urgently needed.

Distant ischemic adaptation (also known as remote ischemic conditioning, RIC) is a non-invasive, safe, and cost-effective intervention that induces endogenous protection against ischemic injury by applying brief, intermittent ischemia to a remote limb. While several large-scale clinical trials (e.g., RICAMIS, RECAST) have demonstrated promising neuroprotective effects of RIC in acute ischemic stroke, results remain inconsistent across studies, particularly in patients with CSVD. Key challenges include the lack of standardized RIC protocols and the absence of specific biomarkers to predict treatment response and elucidate underlying mechanisms.

To address these gaps, this study aims to identify potential effector proteins and specific biomarkers that mediate the therapeutic effects of RIC in patients with cerebral infarction and CSVD. By collecting and analyzing serum samples from RIC-treated patients and controls, we seek to uncover molecular mechanisms underlying RIC-induced neuroprotection and cognitive preservation. The findings may establish a theoretical foundation for optimizing RIC therapy, provide novel drug targets, and ultimately improve clinical outcomes for patients suffering from ischemic stroke and small vessel disease.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged between 50 and 65 years.
  • Definite diagnosis of cerebral infarction or cerebral small vessel disease-related cerebral infarction confirmed by brain MRI or other imaging examinations.
  • Ability to complete the 3-month follow-up and RIC intervention (for the experimental group).
  • Few underlying comorbidities, limited to hypertension and hyperlipidemia; clear consciousness with the ability to provide informed consent.
  • Modified Rankin Scale (mRS) score < 2, with no severe cognitive impairment as assessed by the Montreal Cognitive Assessment (MoCA).
  • Enrolled within 48 hours after the onset of stroke symptoms (i.e., from the time the patient was last known to be well, during the acute phase).

Exclusion Criteria:

  • Complicated with diabetes mellitus, smoking history, or other metabolic disorders.
  • Complicated with other types of stroke (e.g., cardioembolic stroke, large artery atherosclerotic stroke, etc.).
  • Presence of severe cognitive impairment, depression, or other psychiatric or neurological disorders.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Stroke Control Group
standard treatment against stroke
Other: Standard Treatment
Standard Treatment
Experimental: Stroke RIC Group
standard treatment against stroke + RIC intervention
Device: Medical-grade ischemic preconditioning training instrument

The remote ischemic conditioning (RIC) intervention consists of two sessions per day, with 5 cycles per session (each cycle comprising 5 minutes of inflation followed by 5 minutes of deflation), performed alternately on both upper arms. The inflation pressure is set at baseline systolic blood pressure + 20 mmHg, gradually increased up to a maximum of 200 mmHg. If the patient experiences discomfort, the pressure may be appropriately reduced to allow adaptation, then gradually increased again. At least 3 complete cycles must be completed per session, and an overall compliance rate of ≥80% is considered as achieving the target. Concurrently, patients will receive standard medical treatment (antihypertensive therapy, lipid-lowering therapy, and single antiplatelet therapy). The total intervention duration is 3 months.

For enrolled patients with cerebral infarction, management will be conducted by the neurosurgery department. During hospitalization, the RIC procedure will be administered an
Sham Comparator: CSVD Control Group
standard treatment against CSVD
Other: Standard Treatment
Standard Treatment
Experimental: CSVD RIC Group
standard treatment against CSVD + RIC intervention
Device: Medical-grade ischemic preconditioning training instrument

The remote ischemic conditioning (RIC) intervention consists of two sessions per day, with 5 cycles per session (each cycle comprising 5 minutes of inflation followed by 5 minutes of deflation), performed alternately on both upper arms. The inflation pressure is set at baseline systolic blood pressure + 20 mmHg, gradually increased up to a maximum of 200 mmHg. If the patient experiences discomfort, the pressure may be appropriately reduced to allow adaptation, then gradually increased again. At least 3 complete cycles must be completed per session, and an overall compliance rate of ≥80% is considered as achieving the target. Concurrently, patients will receive standard medical treatment (antihypertensive therapy, lipid-lowering therapy, and single antiplatelet therapy). The total intervention duration is 3 months.

For enrolled patients with cerebral infarction, management will be conducted by the neurosurgery department. During hospitalization, the RIC procedure will be administered an

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in White Matter Hyperintensity (WMH) Volume on Brain MRI
Time Frame: Baseline, Month 3
Brain MRI will be performed to assess changes in white matter hyperintensity volume, including lesion extent and DWI signal characteristics. The primary outcome is the change in WMH volume from baseline to 3 months.
Baseline, Month 3
Change in National Institutes of Health Stroke Scale (NIHSS) Score
Time Frame: Baseline, Month 1, Month 3
The NIHSS is a 15-item neurological examination scale used to assess stroke severity. Scores range from 0 to 42, with higher scores indicating more severe neurological deficits. The primary outcome is the change in NIHSS score from baseline to 3 months.
Baseline, Month 1, Month 3
Change in Cognitive Function (MoCA and MMSE Scores)
Time Frame: Baseline, Month 1, Month 3
Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). The MoCA scores range from 0 to 30, with higher scores indicating better cognitive function. The MMSE scores range from 0 to 30, with higher scores indicating better cognitive status. The primary outcome is the change in both scores from baseline to 3 months.
Baseline, Month 1, Month 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Serum Levels of Inflammatory and Neuroprotective Biomarkers
Time Frame: Baseline, Month 1, Month 3
Serum samples will be collected to assess dynamic changes in inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and neuroprotective factors. Changes in biomarker levels will be compared between baseline and follow-up time points.
Baseline, Month 1, Month 3
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Throughout the 3-month intervention period
Safety will be assessed by monitoring the frequency, severity, and relatedness of adverse events and serious adverse events, including allergic reactions, changes in liver and renal function, and coagulation parameters.
Throughout the 3-month intervention period
Compliance Rate with RIC Intervention
Time Frame: Throughout the 3-month intervention period
Adherence to the RIC intervention will be evaluated. Compliance is defined as completing ≥80% of the prescribed RIC sessions (two sessions per day, 5 cycles per session, over 3 months).
Throughout the 3-month intervention period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 25, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 31, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2026-0150

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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