title: MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.
abstract: This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo.
  
  
  
  This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527).
  
  
  
  A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99;P<0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31;P=0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period (P>0.05).
  
  
  
  Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil.
  
  
  
  URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527.
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia. Andrew.bivard@newcastle.edu.au.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bivard
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lillicrap
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnamurthy
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Holliday
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Heather
authors.initials: H
authors.lastname: Pagram
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Parsons
authors.affiliation: From the Departments of Neurology, John Hunter Hospital (A.B., T.L., V.K., M.P., C.R.L.), Hunter Medical Research Institute (A.B., T.L., V.K., E.H., J.A., H.P., M.N., M.P., C.R.L.), and Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (J.A.), University of Newcastle, Australia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications*; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: anxiety; cognition; depression; fatigue; stroke