title: Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.
abstract: Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS.
  
  
  
  Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients.
  
  
  
  ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.
authors.affiliation: Division of Neuropediatrics, University of Basel Children's Hospital, Spitalstrasse 33, Postfach 4031, Basel, Switzerland.|Division of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Division of Neuropediatrics, University of Basel Children's Hospital, Spitalstrasse 33, Postfach 4031, Basel, Switzerland.
authors.forename: Vanya
authors.initials: V
authors.lastname: Gocheva
authors.affiliation: Department of Clinical Research, Clinical Trial Unit, University Hospital Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zumbrunn
authors.affiliation: Division of Neuropediatrics, University of Basel Children's Hospital, Spitalstrasse 33, Postfach 4031, Basel, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rubino-Nacht
authors.affiliation: Division of Neuropediatrics, University of Basel Children's Hospital, Spitalstrasse 33, Postfach 4031, Basel, Switzerland.|Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bonati
authors.affiliation: Division of Neuropediatrics, University of Basel Children's Hospital, Spitalstrasse 33, Postfach 4031, Basel, Switzerland. dirk.fischer@ukbb.ch.|Division of Neurology, University Hospital Basel, Basel, Switzerland. dirk.fischer@ukbb.ch.|Division of Neurology, Medical University Clinic, Kantonsspital Baselland, Bruderholz, Switzerland. dirk.fischer@ukbb.ch.
authors.forename: Dirk
authors.initials: D
authors.lastname: Fischer
authors.affiliation: Division of Neuropediatrics, University of Basel Children's Hospital, Spitalstrasse 33, Postfach 4031, Basel, Switzerland.|Division of Neurology, Medical University Clinic, Kantonsspital Baselland, Bruderholz, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hafner
mesh_terms: D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D016262:Postpoliomyelitis Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D020127:Recovery of Function; D012107:Research Design; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome; D000070857:Walk Test
chemical_list: D015415:Biomarkers; D002956:Citrulline; D009569:Nitric Oxide
keywords: Clinical trial; L-citrulline; Post-polio syndrome; Quantitative MRI