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

NCT07503301 | Enrolling By Invitation DMC

• 1 other identifier: 2026-0150
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke; Small Vessel Cerebrovascular Disease

Keywords

stroke

Outcome Measures

Primary Outcomes (3)

• Change in White Matter Hyperintensity (WMH) Volume on Brain MRI

  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

  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)

  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 Outcomes (3)

• Serum Levels of Inflammatory and Neuroprotective Biomarkers

  Baseline, Month 1, Month 3

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Throughout the 3-month intervention period

• Compliance Rate with RIC Intervention

  Throughout the 3-month intervention period

Study Arms (4)

Stroke Control Group

SHAM COMPARATOR

standard treatment against stroke

Other: Standard Treatment

Stroke RIC Group

EXPERIMENTAL

standard treatment against stroke + RIC intervention

Device: Medical-grade ischemic preconditioning training instrument

CSVD Control Group

SHAM COMPARATOR

standard treatment against CSVD

Other: Standard Treatment

CSVD RIC Group

EXPERIMENTAL

standard treatment against CSVD + RIC intervention

Device: Medical-grade ischemic preconditioning training instrument

Interventions

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

CSVD RIC Group; Stroke RIC Group

Standard Treatment OTHER

Standard Treatment

CSVD Control Group; Stroke Control Group

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

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

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Stroke; Cerebral Small Vessel Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: March 31, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

CN (1)