Fructose for Acute Ischemic Stroke

This is an investigator-initiated, single-center, prospective, randomized, open-label, blinded-endpoint (PROBE) exploratory clinical trial. A total of 46 eligible patients with acute ischemic stroke within 4.5 hours of onset who meet the indications for intravenous thrombolysis will be enrolled. Participants are randomly assigned to an intervention group and a control group.The intervention group receives early intravenous infusion of 250 mL 10% fructose injection combined with standard intravenous thrombolysis and routine stroke background treatment. The control group receives only standard intravenous thrombolysis and conventional medical therapy without fructose intervention. All patients undergo standardized blood pressure and blood glucose management, and antiplatelet therapy is initiated 24 hours after thrombolysis.Neurological function is repeatedly assessed using the National Institutes of Health Stroke Scale (NIHSS) every 12 hours within 72 hours after thrombolysis and daily thereafter. Multimodal brain magnetic resonance examinations including DWI, T2WI and MRS are performed to evaluate cerebral infarct lesion volume, cerebral edema, and neuronal metabolic biomarkers such as NAA, Cho and Lac. The primary outcome is the change in NIHSS score at 7 days after thrombolysis, and cerebral neuronal metabolic characteristics. Secondary outcomes include dynamic neurological recovery, imaging changes of ischemic lesions, 1-month NIHSS score, 1-month modified Rankin Scale (mRS) functional prognosis.Prespecified subgroup analyses are conducted according to baseline neurological deficit severity, age, hypertension history and gender. Safety outcomes monitor adverse events such as hemorrhagic transformation, allergic reactions, liver and renal function abnormalities, blood glucose and electrolyte disorders to evaluate the clinical safety and tolerability of early fructose combined with thrombolysis.An independent clinical endpoint adjudication committee blindly assesses all endpoint events to reduce evaluation bias. Statistical analyses adopt appropriate methods for non-equilibrium small sample data to explore the clinical efficacy, neuronal mitochondrial metabolic regulation mechanism and safety of early fructose injection intervention in acute ischemic stroke patients, so as to provide clinical evidence for early neuroprotective strategy optimization.

Inclusion criteria

• Aged between 18 and 85 years, male and female are both eligible.
• Clinical diagnosis of acute ischemic stroke meeting the diagnostic criteria of Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke.
• Time from stroke onset to hospital admission ≤ 4.5 hours, with new ischemic lesions confirmed by emergency multimodal cranial MRI (DWI/T2WI).
• Meeting the indications for intravenous thrombolysis, without absolute contraindications to thrombolysis, and planned to receive standard intravenous thrombolysis.
• Relatively stable vital signs, able to complete baseline and follow-up cranial MRI examinations including DWI, T2WI and ¹H-MRS, as well as NIHSS and mRS scale assessments.
• The patient or legal representative voluntarily participates in the study and signs written informed consent.

Exclusion criteria

• History of fructose intolerance, abnormal fructose metabolism or hereditary fructose metabolic disorders.
• History of diabetes mellitus or random blood glucose > 11.1 mmol/L.
• Evidence of intracranial hemorrhage on CT scan, symptomatic intracranial hemorrhage, or clinical suspicion of subarachnoid hemorrhage.
• Requiring or intending to continue using restricted medications that may interfere with study safety and implementation.
• Unable to complete cranial MRI examination due to implanted metal materials, claustrophobia or other reasons.
• Any other conditions judged by the investigator to be inappropriate for enrollment.
• Presence of hemorrhagic diathesis, including but not limited to:

• Known hereditary bleeding tendency or severe bleeding disease within the past 6 months;
• Received heparin within 48 hours before enrollment with aPTT exceeding the upper limit of laboratory reference range;
• Current use of vitamin K-dependent oral anticoagulants with INR > 1.7 or PT > 15 s, or current use of novel oral anticoagulants with prolonged aPTT/PT above laboratory upper limit;
• Platelet count < 100,000/mm³ at screening;
• History of central nervous system diseases such as tumor, aneurysm, intracranial or spinal surgery;
• Received traumatic closed-chest cardiac massage, obstetric delivery or non-compressible vascular puncture within the past 10 days;
• Suspected intracranial hemorrhage or aneurysmal subarachnoid hemorrhage;
• Tumors with increased bleeding risk;
• Peptic ulcer disease, esophageal varices, aneurysm, arterial/venous malformation within the past 3 months;
• Any other known diseases associated with significantly elevated bleeding risk.
• Pre-stroke mRS score ≥ 2, combined with dementia or other neurological disabling diseases.
• Complicated with severe medical history affecting endpoint evaluation and follow-up, such as craniocerebral trauma, multiple sclerosis, encephalitis, tumor, poisoning, syphilis, or severe cardiac, pulmonary, hepatic, renal and endocrine diseases.
• Pregnant females.
• Currently participating in another investigational drug or device study, or participation in other experimental treatment within less than 30 days prior to enrollment.
• Combined with severe hepatic and renal insufficiency (eGFR < 30 mL/min/1.73m²).
• Refusal to sign informed consent.