Efficacy of Remote Ischemic Conditioning in Preventing Post-Stroke Depression

Official title

Efficacy of Remote Ischemic Conditioning in Preventing Post-Stroke Depression: A Multicenter, Randomized, Double-Blind, Sham-Controlled Clinical Trial

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.

Detailed description

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.

Interventions

• Device RIC
  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.
• Device Sham-RIC
  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.

Primary outcome measures

• Incidence of post-stroke depression [Time frame: Day 14]

Secondary outcome measures (12)

• Cumulative incidence of post-stroke depression [Time frame: Day 28, Day 90, and Day 180]
• Incidence of post-stroke anxiety [Time frame: Day 180]
• Cumulative incidence of post-stroke anxiety state [Time frame: Day 14, Day 28, Day 90, and Day 180]
• Change from baseline in enlarged perivascular spaces (EPVS) severity score (range 0-4) [Time frame: Day 14]
• Change from baseline in Diffusion Tensor Imaging-Analysis along the Perivascular Space (DTI-ALPS) index. [Time frame: Day 14]
• Change from baseline in Neurotransmitter levels in brain regions [Time frame: Day 14]
• Change from baseline in peripheral blood neurotransmitter levels [Time frame: Day 14]
• Change from baseline in peripheral blood cytokine levels [Time frame: Day 14]
• Change from baseline in 24-item Hamilton Depression Rating Scale (HAMD-24) score (range 0-76) [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) [Time frame: Day 14, Day 28, Day 90, and Day 180]
• Change from baseline in Pittsburgh Sleep Quality Index (PSQI) score (range 0-21) [Time frame: Day 14, Day 28, Day 90, and Day 180]
• Change from baseline in Fugl-Meyer Assessment (FMA) score (range 0-226) [Time frame: Day 14]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

China · 5 centers

• Tongren City People's Hospital — Tongren
• Baoding People's Hospital — Baoding
• Jilin People's Hospital — Jilin City
• Jincheng People's Hospital — Jincheng
• Xuanwu Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT06920706 · LYS[2025]039-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗