Clinical Research Directory

Inclusion Criteria: 1. Age ≥ 30 years; 2. Clinical lacunar syndrome within 7 days; 3. Brain CT/MRI after symptom onset: 1. a relevant (in time and location) acute lacunar infarct; 2. if no relevant lesion, symptom duration \>24 hours, with no other suspected stroke etiologies (such as cerebral hemorrhage, cortical infarction, seizures, etc.) 4. MoCA score meeting the following criteria: 1. MoCA ≥ 13 if educated ≤ 6 years; 2. MoCA ≥ 15 if 7 ≤ educated ≤ 12 years; 3. MoCA ≥ 18 if educated ≥ 13 years； 5. mRS ≤ 1 prior to this episode; 6. Patient or a legally authorized representative signed informed consent. Exclusion Criteria: 1. Ischemic stroke of large artery atherosclerosis, cardioembolism, or other etiologies (TOAST classification); 2. Diagnosed or suspected hereditary CSVD; 3. Intracerebral hemorrhage within the past 3 months including parenchymal, intraventricular, subarachnoid hemorrhage, subdural/epidural hematoma; 4. Neurodegenerative diseases or systemic diseases that may lead to cognitive impairment, such as Alzheimer's disease, mixed dementia, Parkinson's disease, systemic autoimmune diseases, hepatic encephalopathy, or uremic encephalopathy. 5. Previously diagnosed psychiatric disorders (DSM-5 criteria). 6. Other active neurological disorders (e.g., recurrent seizures, brain tumors, vascular malformations, untreated aneurysms \>3 mm). 7. Hypotension (seated systolic blood pressure \<100 mmHg), bradycardia (heart rate \<60 bpm), sick sinus syndrome or severe cardiopulmonary disease. 8. History of congestive heart failure, acute myocardial infarction or other severe cardiac dysfunctions (NYHA Class III-IV). 9. Coagulation disorders, bleeding tendency or systemic bleeding, including but not limited to prothrombin time \>3×upper limit of normal (ULN), platelet count \<50×109/L, hemophilia, capillary fragility, gastrointestinal bleeding, urinary tract bleeding, hemoptysis, or vitreous hemorrhage, etc. 10. Severe hepatic or renal insufficiency (note: severe hepatic insufficiency is defined as ALT or AST \> 3×ULN or acute hepatitis, chronic active hepatitis, cirrhosis; severe renal insufficiency is defined as eGFR \< 45 ml/min/1.73m², creatinine clearance \< 40 ml/min, or known chronic kidney disease of stage 3 or higher). 11. Head trauma, intracranial or spinal surgery, major surgical procedures or severe trauma within the past 4 weeks. 12. ISMN or NBP use within the past 3 days. 13. Have contraindications to ISMN or NBP, or allergy to their components. 14. Have to use the contraindicated drugs of this trial for a long time. 15. Pregnant, breastfeeding or planning to pregnant during this study. 16. Unable to tolerate MRI or with MRI contraindications. 17. Have severe diseases or expected survival \<12 months. 18. Participate in other clinical trials within 30 days before this trial. 19. Unlikely to comply with study procedures and follow-up procedures for whatever reason in the opinion of the research physician.