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Enrolling by Invitation

NCT Number: NCT07503301

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

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.

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Key information

Conditions

Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Nervous System Diseases Small Vessel Cerebrovascular Disease Vascular Diseases

Age range

50 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Hangzhou, Zhejiang, 310000, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Medical-grade ischemic preconditioning training instrument

Device

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

standard treatment

Other

Standard Treatment

Primary outcomes

  1. 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.

  2. 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.

  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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

Sponsors and collaborators

Lead sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Other

Registry information

Official study title

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

Acronym: SHIELD

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Mar 31, 2026
Registry last updated
Mar 31, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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