Clinical trial NCT06920706: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Post-stroke Depression
Remote Ischemic Conditioning
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2025-04-10
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Primary outcomes:
measure: Incidence of post-stroke depression
timeFrame: Day 14
Secondary outcomes:
measure: Cumulative incidence of post-stroke depression
timeFrame: Day 28, Day 90, and Day 180
measure: Incidence of post-stroke anxiety
timeFrame: Day 180
measure: Cumulative incidence of post-stroke anxiety state
timeFrame: Day 14, Day 28, Day 90, and Day 180
measure: Change from baseline in enlarged perivascular spaces (EPVS) severity score (range 0-4)
timeFrame: Day 14
measure: Change from baseline in Diffusion Tensor Imaging-Analysis along the Perivascular Space (DTI-ALPS) index.
timeFrame: Day 14
measure: Change from baseline in Neurotransmitter levels in brain regions
timeFrame: Day 14
measure: Change from baseline in peripheral blood neurotransmitter levels
timeFrame: Day 14
measure: Change from baseline in peripheral blood cytokine levels
timeFrame: Day 14
measure: Change from baseline in 24-item Hamilton Depression Rating Scale (HAMD-24) score (range 0-76)
timeFrame: Day 14, Day 28, Day 90, and Day 180
measure: Change from baseline in 14-item Hamilton Anxiety Rating Scale (HAMA-14) score (range 0-56)
timeFrame: Day 14, Day 28, Day 90, and Day 180
measure: Change from baseline in Pittsburgh Sleep Quality Index (PSQI) score (range 0-21)
timeFrame: Day 14, Day 28, Day 90, and Day 180
measure: Change from baseline in Fugl-Meyer Assessment (FMA) score (range 0-226)
timeFrame: Day 14
measure: Change from baseline in National Institutes of Health Stroke Scale (NIHSS) score (range 0-42)
timeFrame: Day 14
measure: Change from baseline in Mini-Mental State Examination (MMSE) score (range 0-30)
timeFrame: Day 90 and Day 180
measure: Change from baseline in EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) score (range 5-25)
timeFrame: Day 90 and Day 180
measure: Change from baseline in EuroQol 5-Dimension 5-Level questionnaire Visual Analogue Scale (EQ-5D-5L VAS) score (range 0-100)
timeFrame: Day 90 and Day 180
measure: The proportion of modified Rankin Scale (mRS) Score 0-2
timeFrame: Day 90 and Day 180
measure: The distribution of modified Rankin Scale (mRS) Score (range 0-6)
timeFrame: Day 90 and Day 180
measure: All-cause mortality
timeFrame: Day 180
measure: Total hospitalization time
timeFrame: Day 180
Other outcomes:
measure: Incidence of adverse events
timeFrame: Day 14, Day 28, Day 90, and Day 180
measure: Incidence of serious adverse events
timeFrame: Day 14, Day 28, Day 90, and Day 180
Locations:
city: Tongren
country: China
facility: Tongren City People's Hospital
state: Guizhou
city: Baoding
country: China
facility: Baoding People's Hospital
state: Hebei
city: Jilin
country: China
facility: Jilin People's Hospital
state: Jilin
city: Jincheng
country: China
facility: Jincheng People's Hospital
state: Shanxi
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Lina Jia
role: STUDY_DIRECTOR
References: