Fructose for Acute Ischemic Stroke (FRUCTOSE-AIS)

Clinical Study of Fructose Injection in the Treatment of Acute Ischemic Stroke

This is a single-center, prospective, randomized, open-label, blinded-endpoint exploratory clinical study enrolling 46 patients with acute ischemic stroke. All eligible patients have symptom onset within 4.5 hours, meet intravenous thrombolysis indications, and receive standard thrombolysis and routine stroke treatment. Participants are randomly assigned to two groups: the intervention group receives early intravenous infusion of 10% fructose injection plus standard treatment, while the control group receives only standard treatment without fructose. The study mainly evaluates changes in neurological function via NIHSS scores within 7 days after thrombolysis, assesses cerebral infarct lesion volume and brain edema using multimodal MRI including DWI, T2WI and MRS, detects cerebral neuronal metabolic markers, and conducts 1-month follow-up of neurological function by NIHSS score as well as functional prognosis using the mRS score. The research also comprehensively monitors adverse events and safety indicators to explore the clinical efficacy, neuronal metabolic regulation effect and safety of early fructose injection combined with intravenous thrombolysis in acute ischemic stroke patients, aiming to provide clinical evidence for early neuroprotective intervention.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: 10% Fructose Injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Feng professor, PhD; Phone Number: 0516-83353238; Email: xyfysjnkfy@163.com

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • Xuzhou Medical University Affiliated Hospital
      • Contact: Yu Feng Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged between 18 and 85 years, male and female are both eligible.
2. Clinical diagnosis of acute ischemic stroke meeting the diagnostic criteria of Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke.
3. Time from stroke onset to hospital admission ≤ 4.5 hours, with new ischemic lesions confirmed by emergency multimodal cranial MRI (DWI/T2WI).
4. Meeting the indications for intravenous thrombolysis, without absolute contraindications to thrombolysis, and planned to receive standard intravenous thrombolysis.
5. 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.
6. The patient or legal representative voluntarily participates in the study and signs written informed consent.

Exclusion Criteria:

1. History of fructose intolerance, abnormal fructose metabolism or hereditary fructose metabolic disorders.
2. History of diabetes mellitus or random blood glucose > 11.1 mmol/L.
3. Evidence of intracranial hemorrhage on CT scan, symptomatic intracranial hemorrhage, or clinical suspicion of subarachnoid hemorrhage.
4. Requiring or intending to continue using restricted medications that may interfere with study safety and implementation.
5. Unable to complete cranial MRI examination due to implanted metal materials, claustrophobia or other reasons.
6. Any other conditions judged by the investigator to be inappropriate for enrollment.

7. 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.
8. Pre-stroke mRS score ≥ 2, combined with dementia or other neurological disabling diseases.
9. 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.
10. Pregnant females.
11. Currently participating in another investigational drug or device study, or participation in other experimental treatment within less than 30 days prior to enrollment.
12. Combined with severe hepatic and renal insufficiency (eGFR < 30 mL/min/1.73m²).
13. Refusal to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fructose Injection plus Standard Thrombolysis Treatment; Patients receive early intravenous infusion of 250 mL 10% fructose injection immediately after admission, followed by standard intravenous thrombolysis and routine standardized medical treatment for acute ischemic stroke. Unified blood pressure and blood glucose management are performed in all participants, and antiplatelet therapy is initiated 24 hours after thrombolysis.	Drug: 10% Fructose Injection; Single intravenous infusion of 250 mL 10% fructose injection administered as early as possible within the ischemic stage, combined with standard intravenous thrombolysis and standardized basic treatment for acute ischemic stroke. Unified blood pressure and blood glucose management are implemented, and antiplatelet therapy is started 24 hours after thrombolysis.
No Intervention: Standard Thrombolysis Alone Without Fructose; Patients receive only standard intravenous thrombolysis and routine standardized medical treatment for acute ischemic stroke without additional fructose injection. All participants receive the same unified blood pressure, blood glucose control and antiplatelet therapy regimen as the intervention group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day change in National Institutes of Health Stroke Scale (NIHSS) score	Absolute change in NIHSS score, calculated as follow-up score minus pre-intravenous thrombolysis (pre-IVT) baseline score, assessed at 7 days after intravenous thrombolysis (IVT). The full scale is the National Institutes of Health Stroke Scale; total score ranges from 0 to 42, and higher scores indicate more severe neurological deficits.	Baseline to 7 days after thrombolysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of N-acetylaspartate (NAA) detected by proton magnetic resonance spectroscopy (¹H-MRS)	Absolute changes in the levels of N-acetylaspartate (NAA) in the ischemic penumbra and infarct core, calculated from pre-IVT baseline to 24 hours after IVT. Relative quantification; no absolute concentration determined. Metabolite signal intensities are reported in arbitrary units (a.u.) normalized to internal reference (e.g., total NAA or water signal). Unit of measure: Arbitrary units	Pre-IVT baseline to 24 hours post-IVT (±2 hours)
Levels of choline (Cho) detected by proton magnetic resonance spectroscopy (¹H-MRS)	Absolute changes in the levels of choline (Cho) in the ischemic penumbra and infarct core, calculated from pre-IVT baseline to 24 hours after IVT. Relative quantification; no absolute concentration determined. Metabolite signal intensities are reported in arbitrary units (a.u.) normalized to internal reference (e.g., total Cho or water signal). Unit of measure: Arbitrary units	Time Frame: Pre-IVT baseline to 24 hours post-IVT (±2 hours)
Levels of creatine (Cr) detected by proton magnetic resonance spectroscopy (¹H-MRS)	Absolute changes in the levels of creatine (Cr) in the ischemic penumbra and infarct core, calculated from pre-IVT baseline to 24 hours after IVT. Relative quantification; no absolute concentration determined. Metabolite signal intensities are reported in arbitrary units (a.u.) normalized to internal reference (e.g., total Cr or water signal). Arbitrary units	Pre-IVT baseline to 24 hours post-IVT (±2 hours)
NAA/Cr ratio derived from ¹H-MRS	Absolute change in N-acetylaspartate/creatine (NAA/Cr) ratio in the ischemic penumbra and infarct core, calculated from pre-IVT baseline to 24 hours after IVT. Unit of measure: Ratio (no unit)	Pre-IVT baseline to 24 hours post-IVT (±2 hours)
Cho/Cr ratio derived from ¹H-MRS	Absolute change in choline/creatine (Cho/Cr) ratio in the ischemic penumbra and infarct core, calculated from pre-IVT baseline to 24 hours after IVT. Time Frame: Pre-IVT baseline to 24 hours post-IVT (±2 hours). Unit of measure: Ratio (no unit)	Time Frame: Pre-IVT baseline to 24 hours post-IVT (±2 hours)
1-month change in National Institutes of Health Stroke Scale (NIHSS) score	Absolute change in NIHSS score, calculated as follow-up score minus pre-IVT baseline score, assessed at 1 month after IVT. The full scale is the National Institutes of Health Stroke Scale; total score ranges from 0 to 42, and higher scores indicate more severe neurological deficits.	Pre-IVT baseline to 1 month post-IVT (±7 days)
1-month functional outcome assessed by modified Rankin Scale (mRS)	Description: Functional status classified into favorable and unfavorable outcomes at 1 month after IVT. Favorable outcome: mRS score 0-2 (no or mild disability, independent in activities of daily living). Unfavorable outcome: mRS score 3-6 (moderate to severe disability, dependent in activities of daily living, or death for mRS score 6). The full scale is the modified Rankin Scale; total score ranges from 0 to 6, and higher scores indicate greater functional disability.	Pre-IVT baseline to 1 month post-IVT (±7 days)

Collaborators and Investigators

• Sponsor: Ji Xunming,MD,PhD

Publications and helpful links

General Publications

• Zhang D, Feng Y, Pan H, Xuan Z, Yan S, Mao Y, Xiao X, Huang X, Zhang H, Zhou F, Chen B, Chen X, Liu H, Yan X, Liang H, Cui W. 9-Methylfascaplysin exerts anti-ischemic stroke neuroprotective effects via the inhibition of neuroinflammation and oxidative stress in rats. Int Immunopharmacol. 2021 Aug;97:107656. doi: 10.1016/j.intimp.2021.107656. Epub 2021 Apr 23.
• Tian Y, Su Y, Ye Q, Chen L, Yuan F, Wang Z. Silencing of TXNIP Alleviated Oxidative Stress Injury by Regulating MAPK-Nrf2 Axis in Ischemic Stroke. Neurochem Res. 2020 Feb;45(2):428-436. doi: 10.1007/s11064-019-02933-y. Epub 2019 Dec 19.
• Marek G, Pannu V, Shanmugham P, Pancione B, Mascia D, Crosson S, Ishimoto T, Sautin YY. Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway. Diabetes. 2015 Feb;64(2):508-18. doi: 10.2337/db14-0411. Epub 2014 Sep 3.
• Kim YN, Jung HY, Eum WS, Kim DW, Shin MJ, Ahn EH, Kim SJ, Lee CH, Yong JI, Ryu EJ, Park J, Choi JH, Hwang IK, Choi SY. Neuroprotective effects of PEP-1-carbonyl reductase 1 against oxidative-stress-induced ischemic neuronal cell damage. Free Radic Biol Med. 2014 Apr;69:181-96. doi: 10.1016/j.freeradbiomed.2014.01.006. Epub 2014 Jan 17.
• Hayasaki T, Ishimoto T, Doke T, Hirayama A, Soga T, Furuhashi K, Kato N, Kosugi T, Tsuboi N, Lanaspa MA, Johnson RJ, Maruyama S, Kadomatsu K. Fructose increases the activity of sodium hydrogen exchanger in renal proximal tubules that is dependent on ketohexokinase. J Nutr Biochem. 2019 Sep;71:54-62. doi: 10.1016/j.jnutbio.2019.05.017. Epub 2019 Jun 8.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 23, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Fructose; Neuroprotection; Acute ischemic stroke; NIHSS; Intravenous thrombolysis; Brain magnetic resonance spectroscopy; Cerebral energy metabolism
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Carbohydrates; Sugars; Hexoses; Monosaccharides; Ketoses; Fructose
• Other Study ID Numbers: AIS-FRUCTOSE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A definitive plan for sharing individual participant data (IPD) has not yet been established at this stage. The feasibility and specific modalities of IPD sharing will be further evaluated and determined based on study progress, ethics committee approval, and relevant regulatory requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No