Efficacy of Remote Ischemic Conditioning in Preventing Post-Stroke Depression

N/ANot Yet RecruitingNCT06920706

Xuanwu Hospital, Beijing240 enrolled

Overview

Post-stroke depression (PSD) is characterized primarily by low mood and loss of interest following a stroke. It is one of the most common and serious complications of stroke, with an incidence of 11% to 41% within two years post-stroke. PSD significantly impacts stroke prognosis, not only hindering neurological recovery but also increasing clinical disability and mortality rates, thereby imposing substantial economic and psychological burdens on families and society. Therefore, preventing PSD is crucial for stroke rehabilitation. Clinical trials have demonstrated that preventive antidepressant treatment can reduce PSD incidence and improve clinical outcomes; however, controversies remain regarding the timing, methods, and safety. Meanwhile, preventive psychological therapy faces challenges in implementation due to effectiveness, accessibility, and cost-effectiveness. Remote ischemic preconditioning (RIC) is a non-invasive, cost-effective, and non-pharmacological intervention. By modulating small molecules in the peripheral and central nervous systems through transient, periodic limb blood flow restriction and reperfusion, RIC reverses neurobiological changes and demonstrates neuroprotective potential in various neurological diseases. Recently, a study showed that RIC is safe and effective in preventing PSD; however, the sample size is small and the specific mechanisms remain unclear. Therefore, this study aims to further explore the role and mechanisms of RIC in PSD prevention.

This multicenter, randomized, double-blind, sham controlled clinical study will enroll acute ischemic stroke patients within 48 hours of symptom onset. Eligible participants will be randomly allocated (1:1) to receive either remote ischemic conditioning (RIC) or sham-RIC treatment for 14 consecutive days. The primary outcome is the incidence of post-stroke depression at day 14 post-randomization.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Interventions

RICDEVICE

The ischemic preconditioning training device is applied to the subjects' upper arms to administer pressure (200 mmHg). The pressure is maintained for 5 minutes, followed by 5 minutes of release, completing one ischemia-reperfusion cycle. Each training session consists of 5 consecutive cycles, performed twice daily for 14 days.

Sham-RICDEVICE

The ischemic preconditioning training device is applied to the subjects' upper arms to administer pressure (60 mmHg). The pressure is maintained for 5 minutes, followed by 5 minutes of release, completing one ischemia-reperfusion cycle. Each training session consists of 5 consecutive cycles, performed twice daily for 14 days.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient age≥18 years; * No gender preference; * Diagnosed with acute ischemic stroke; * From onset to treatment ≤48 h; * 6≤ NIHSS scores ≤25; * Premorbid mRS ≤1; * Signed informed consent. Exclusion Criteria: * Baseline HAMD-24 scores ≥8; * Infarction area overlapped with the area where the DTI-ALPS index is calculated; * A history of severe mental illness such as depression, bipolar disorder, and schizophrenia; * A history of mental disorders caused by other organic diseases, such as post-Parkinson depression; * Participants with cognitive impairment, disturbance of consciousness, severe hearing impairment, or aphasia who were unable to cooperate with the assessment; * A history of autoimmune diseases (such as multiple sclerosis, neuromyelitis optica spectrum disorders, systemic lupus erythematosus, etc.), malignant tumors, or obstructive sleep apnea hypopnea syndrome; * Intracranial tumor, arteriovenous malformation, or aneurysm; * Uncontrolled severe hypertension (systolic pressure \>180mmHg or diastolic pressure \>110 mmHg after drug treatment) ; * Subclavian artery stenosis≥50% or subclavian steal syndrome; * Any contraindication for remote ischemic adaptation: the upper limb has serious soft tissue injury, fracture or vascular injury, distal upper limb perivascular lesions, etc.; * Severe coagulation dysfunction, platelet count \< 100×10\^9/L, cardiac dysfunction (NYHA class Ⅲ or above), hepatic dysfunction (aspartate aminotransferase and/or alanine aminotransferase \> 3 times the upper limit of normal), or renal dysfunction (serum creatinine \> 265μmol/L); * Any contraindication for magnetic resonance imaging: metal implants, claustrophobia, etc.; * Women known to be pregnant or lactating, or have a positive pregnancy test; * Participating in other clinical trials within three months; * Participants not suitable for this clinical studies considered by researcher.

Locations (5)

Tongren City People's Hospital

Tongren, Guizhou, China

Baoding People's Hospital

Baoding, Hebei, China

Jilin People's Hospital

Jilin City, Jilin, China

Jincheng People's Hospital

Jincheng, Shanxi, China

Xuanwu Hospital, Capital Medical University

Beijing, China

Outcomes

Primary Outcomes

Incidence of post-stroke depression

The diagnosis of post-stroke depression is established according to the "Depressive Disorder Due to Another Medical Condition" criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), using the Structured Clinical Interview for DSM-5 Disorders, Research Version (SCID-5-RV).

Time frame: Day 14

Secondary Outcomes

Cumulative incidence of post-stroke depression

The cumulative incidence of post-stroke depression is calculated as (number of post-stroke depression cases during follow-up / total enrolled participants) × 100%.

Time frame: Day 28, Day 90, and Day 180

Incidence of post-stroke anxiety

The diagnosis of post-stroke anxiety is established according to the "Anxiety Disorder Due to Another Medical Condition" criteria specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), using the Structured Clinical Interview for DSM-5 Disorders, Research Version (SCID-5-RV).

Time frame: Day 180

Cumulative incidence of post-stroke anxiety state

Post-stroke anxiety state is defined as a 14-item Hamilton Anxiety Rating Scale (HAMA-14) score ≥7 points.

Time frame: Day 14, Day 28, Day 90, and Day 180

Change from baseline in enlarged perivascular spaces (EPVS) severity score (range 0-4)

EPVS in the basal ganglia (BG) and centrum semiovale (CSO) are visually scored as: 0 = none, 1 = 1-10, 2 = 11-20, 3 = 21-40, and 4 = \>40 on the axial slice with the highest burden and hemicerebrum with higher burden. The higher the score, the worse the outcome.

Time frame: Day 14

Change from baseline in Diffusion Tensor Imaging-Analysis along the Perivascular Space (DTI-ALPS) index.

The DTI-ALPS index is calculated as the ratio of projection-to-association fiber diffusivity in the lateral ventricular region.

Time frame: Day 14

Change from baseline in Neurotransmitter levels in brain regions

Proton magnetic resonance spectroscopy (¹H-MRS) is performed to quantify the levels of N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline (Cho), and creatine (Cr) in the following brain regions: thalamus, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, insular cortex, medial prefrontal cortex, and cingulate cortex.

Time frame: Day 14

Change from baseline in peripheral blood neurotransmitter levels

Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), norepinephrine (NE), and dopamine (DA) in peripheral blood are measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Time frame: Day 14

Change from baseline in peripheral blood cytokine levels

Levels of interleukin (IL)-1β, IL-6, IL-10, IL-15, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β) in peripheral blood are measured using enzyme-linked immunosorbent assay (ELISA).

Time frame: Day 14

Change from baseline in 24-item Hamilton Depression Rating Scale (HAMD-24) score (range 0-76)

The HAMD-24 is a standardized, clinician-rated instrument for quantifying depression severity, where elevated scores correlate with increased symptom burden.

Time frame: Day 14, Day 28, Day 90, and Day 180

Change from baseline in 14-item Hamilton Anxiety Rating Scale (HAMA-14) score (range 0-56)

The HAMA-14 is a standardized, clinician-rated instrument for quantifying anxiety severity, with higher scores indicating greater severity.

Time frame: Day 14, Day 28, Day 90, and Day 180

Change from baseline in Pittsburgh Sleep Quality Index (PSQI) score (range 0-21)

The PSQI is a validated self-reported questionnaire assessing sleep quality and disturbances over a 1-month period. Higher scores indicate worse sleep quality.

Time frame: Day 14, Day 28, Day 90, and Day 180

Change from baseline in Fugl-Meyer Assessment (FMA) score (range 0-226)

The FMA is administered to evaluate sensorimotor recovery post-stroke. Higher total scores indicate better functional recovery.

Time frame: Day 14

Change from baseline in National Institutes of Health Stroke Scale (NIHSS) score (range 0-42)

The NIHSS is assessed to quantify neurological deficit severity. Higher scores indicate more severe impairment.

Time frame: Day 14

Change from baseline in Mini-Mental State Examination (MMSE) score (range 0-30)

The MMSE is administered to assess global cognitive function, with lower scores indicating greater impairment.