title: Remote ischemic preconditioning in the prevention of ischemic brain damage during intracranial aneurysm treatment (RIPAT): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  The treatment of intracranial aneurysms may be associated with cerebral ischemia. We hypothesize that pre-interventional remote ischemic preconditioning (RIPC) reduces ischemic cerebral tissue damage in patients undergoing elective intracranial aneurysm treatment.
  
  
  METHODS
  This study is a single-center, prospective, randomized, double-blind explorative trial. Patients with an unruptured intracranial aneurysm admitted to Innsbruck Medical University Hospital for coiling or clipping will be consecutively randomized to either the intervention group (= RIPC by inflating an upper extremity blood-pressure cuff for 3 x 5 min to 200 mmHg) or the control group after induction of anesthesia. Participants will be randomized 1:1 to either the preconditioning group or the sham group using a random allocation sequence and block randomization. The precalculated sample size is n = 24 per group. The primary endpoint is the area-under-the-curve concentration of serum biomarkers (S100B, NSE, GFAP, MMP9, MBP, and cellular microparticles) in the first five days after treatment. Secondary endpoints are the number and volume of new ischemic lesions in magnetic resonance imaging and clinical outcome evaluated with the National Institutes of Health Stroke Scale, the modified Rankin Scale, and neuropsychological tests at six and twelve months. All outcome variables will be determined by observers blinded to group allocation. This study was approved by the local institutional Ethics Committee (UN5164), version 3.0 of the study protocol, dated 20 October 2013.
  
  
  CONCLUSIONS
  This study uses the elective treatment of intracranial aneurysms as a paradigmatic situation to explore the neuroprotective effects of RIPC. If effects are demonstrable in this pilot trial, a larger, prospective phase III trial will be considered.
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, 35, Anichstrasse, Innsbruck, 6020, Austria. Selma.Tuelue@i-med.ac.at.
authors.forename: Selma
authors.initials: S
authors.lastname: Tülü
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, 35, Anichstrasse, Innsbruck, 6020, Austria. Miriam.Mulino@tirol-kliniken.at.
authors.forename: Miriam
authors.initials: M
authors.lastname: Mulino
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, 35, Anichstrasse, Innsbruck, 6020, Austria. Daniel.Pinggera@tirol-kliniken.at.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinggera
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, 6020, Austria. Markus.Luger@tirol-kliniken.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Luger
authors.affiliation: Central Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Innsbruck, Innsbruck, 6020, Austria. Philipp.Wuertinger@tirol-kliniken.at.
authors.forename: Philipp
authors.initials: P
authors.lastname: Würtinger
authors.affiliation: Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, 6020, Austria. Astrid.Grams@i-med.ac.at.
authors.forename: Astrid
authors.initials: A
authors.lastname: Grams
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, 6020, Austria. Thomas.Bodner@tirol-kliniken.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bodner
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, 6020, Austria. Ronny.Beer@i-med.ac.at.
authors.forename: Ronny
authors.initials: R
authors.lastname: Beer
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, 6020, Austria. Raimund.Helbok@tirol-kliniken.at.
authors.forename: Raimund
authors.initials: R
authors.lastname: Helbok
authors.affiliation: Department of Public Health and Health Technology Assessment, UMIT Health and Life Sciences University, Hall in Tirol, Austria. Raffaella.Gothe@umit.at.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Matteucci-Gothe
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, 35, Anichstrasse, Innsbruck, 6020, Austria. Claudia.Unterhofer@tirol-kliniken.at.
authors.forename: Claudia
authors.initials: C
authors.lastname: Unterhofer
authors.affiliation: Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, 6020, Austria. Elke.Gizewski@i-med.ac.at.
authors.forename: Elke
authors.initials: E
authors.lastname: Gizewski
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, 6020, Austria. Erich.Schmutzhard@i-med.ac.at.
authors.forename: Erich
authors.initials: E
authors.lastname: Schmutzhard
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, 35, Anichstrasse, Innsbruck, 6020, Austria. Claudius.Thome@i-med.ac.at.
authors.forename: Claudius
authors.initials: C
authors.lastname: Thomé
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, 35, Anichstrasse, Innsbruck, 6020, Austria. Martin.Ortler@i-med.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Ortler
mesh_terms: D001317:Austria; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002985:Clinical Protocols; D004185:Disability Evaluation; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D057510:Endovascular Procedures / Q000009:adverse effects*; D006785:Hospitals, University; D006801:Humans; D002532:Intracranial Aneurysm / Q000175:diagnosis / Q000601:surgery / Q000628:therapy*; D019194:Ischemic Preconditioning / Q000009:adverse effects / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008866:Microsurgery / Q000009:adverse effects*; D009483:Neuropsychological Tests; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D011446:Prospective Studies; D012039:Regional Blood Flow; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D034941:Upper Extremity / Q000098:blood supply*
chemical_list: D015415:Biomarkers