title: Modafinil In Debilitating fatigue After Stroke (MIDAS): study protocol for a randomised, double-blinded, placebo-controlled, crossover trial.
abstract: Fatigue is a common symptom in stroke survivors for which there is currently no proven therapy. Modafinil is a wakefulness-promoting agent with established benefits in other disease models. We aim to test if modafinil will improve patient's self-reported fatigue scores when compared to placebo and if therapy results in increased quality of life.
  
  
  
  MIDAS is a phase II, single-centre, prospective, double-blinded, randomised, crossover trial of modafinil for the treatment of persistent fatigue in survivors of ischaemic stroke. The inclusion criteria will require an average score of 12 or more across all domains of the Multi-dimensional Fatigue Inventory (MFI-20) and the diagnosis of a stroke more than 6 months prior. Patients will be randomised 1:1 to receive either modafinil 200 mg daily or placebo for a period of 6 weeks, after which a crossover will occur where patients who are on modafinil will begin taking placebo and vice versa. The primary outcome will be improvement in fatigue as measured by the MFI-20. Secondary outcomes will include changes in the Fatigue Severity Scale, improved cognition measured using the Montreal Cognitive Assessment, improvement in mood as determined by the Depression, Anxiety and Stress Scale and improvement in each patient's stroke-specific quality of life score. All participants will also undergo magnetic resonance imaging (MRI) at baseline, crossover and study conclusion to measure cerebral blood flow on arterial spin labelling and brain activity on resting state functional MRI. This study will comply with the CONSORT guidelines. The projected sample size requirement is 36 participants in a crossover trial giving a power of 80 % and a type-1 error rate of 0.05.
  
  
  
  MIDAS seeks to enhance the quality of life in stroke survivors by assisting or resolving stroke-associated fatigue.
  
  
  
  ACTRN12615000350527 , registered on the 17 April 2015. Protocol version 3, approved 16 June 2015.
authors.affiliation: Departments of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.|Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lillicrap
authors.affiliation: Departments of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.|Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnamurthy
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Departments of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.|Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
authors.affiliation: Departments of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia.|Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.affiliation: Departments of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia. Andrew.bivard@hotmail.com.|Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia. Andrew.bivard@hotmail.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bivard
mesh_terms: D000339:Affect / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging; D000077408:Modafinil; D009517:New South Wales; D011446:Prospective Studies; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications* / Q000503:physiopathology / Q000523:psychology; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: Fatigue; Ischaemic stroke; Stroke recovery