title: Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial.
abstract: BACKGROUND
  Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke treated within the first 4.5 hours of symptom onset.
  
  
  RESULTS
  In this multicenter trial, we randomly assigned 25 eligible patients with hemispheric ischemic stroke stemming from anterior or middle cerebral arterial occlusion to receive alteplase alone and 22 patients to receive alteplase plus oral fingolimod 0.5 mg daily for 3 consecutive days within 4.5 hours of the onset of ischemic stroke. Compared with patients who received alteplase alone, patients who received the combination of fingolimod with alteplase exhibited lower circulating lymphocytes, smaller lesion volumes (10.1 versus 34.3 mL; P=0.04), less hemorrhage (1.2 versus 4.4 mL; P=0.01), and attenuated neurological deficits in National Institute of Health Stroke Scales (4 versus 2; P=0.02) at day 1. Furthermore, restrained lesion growth from day 1 to 7 (-2.3 versus 12.1 mL; P<0.01) with a better recovery at day 90 (modified Rankin Scale score 0-1, 73% versus 32%; P<0.01) was evident in patients given fingolimod and alteplase. No serious adverse events were recorded in all patients.
  
  
  CONCLUSIONS
  In this pilot study, combination therapy of fingolimod and alteplase was well tolerated, attenuated reperfusion injury, and improved clinical outcomes in patients with acute ischemic stroke. These findings need to be tested in further clinical trials.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02002390.
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.|Department of Neurology, Tianjin HuanHu Hospital, Tianjin, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Decai
authors.initials: D
authors.lastname: Tian
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chang
authors.affiliation: Department of Neurology, Tianjin Forth Central Hospital, Tianjin, China.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.|Department of Neurology, Tianjin HuanHu Hospital, Tianjin, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Neurology and Neuroscience Associates, Unity Health Network, Akron, OH.
authors.forename: Deren
authors.initials: D
authors.lastname: Huang
authors.affiliation: Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.|Department of Neurology, Tianjin HuanHu Hospital, Tianjin, China.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004489:Edema, Cardiac / Q000517:prevention & control*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010865:Pilot Projects; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D007155:Immunologic Factors; D010959:Tissue Plasminogen Activator; D000068876:Fingolimod Hydrochloride
keywords: brain ischemia; edema; hemorrhage; inflammation; thrombolytic therapy