MIDAS (Modafinil in Debilitating Fatigue After Stroke)

Abstract

Background and Purpose—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.Methods—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).Results—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).Conclusions—Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil.Clinical Trial Registration—URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527.

Post-stroke fatigue: a scoping review

“…Most of the interventional studies have a medium to high risk of bias. Table 2 shows only two studies in white cells (indicating low risk of bias) but both have small sample size consisting of 34 (MIDAS study 63 – 68 ) and 64 randomised patients 61 respectively.…”

“…The dominance of single-centred interventional studies with small sample sizes and interventions delivered within a 12-week period may be the reasons for absence of follow-up studies. MIDAS (interventional) 63 – 65 and NotFAST (observational) 81 – 85 are the only recent studies with novel and potentially long-term findings with larger sample size (in case of MIDAS 2) 103 or with the intention to design an intervention (NotFAST2) 104 .…”

Short- and Long-Term Efficacy of Modafinil at Improving Quality of Life in Stroke Survivors: A Post Hoc Sub Study of the Modafinil in Debilitating Fatigue After Stroke Trial

“…Beta coefficients with their 95% confidence intervals and Pearson’s correlation coefficients were estimated. Differences in pre- and post-treatment quality of life were compared to differences in pre- and post-treatment fatigue, which had been demonstrated to be improved by modafinil ( 2 ). Treatment effects and interactions between treatment and baseline measures were assessed using linear regression including fixed effects for participant, treatment (modafinil or placebo), baseline outcome measure, and interaction between treatment and baseline measure.…”

“…Approximately 40% of stroke survivors experience debilitating fatigue 3 months or more after their stroke which can negatively impact their quality of life, interfering with their ability to participate in rehabilitation and return to everyday activities such as work and socialization ( 1 ). We recently investigated the effectiveness of the wakefulness-promoting agent modafinil in stroke survivors as part of the modafinil in debilitating fatigue after stroke (MIDAS) trial ( 2 ). During MIDAS, participants reported a significant decrease in fatigue following 6 weeks of modafinil therapy (200 mg/day) and a concurrent improvement in self-reported quality of life.…”

Behavioral Changes in Combination Therapy of Ethanol and Modafinil on rats Focal Cerebral Ischemia

“…Recent studies have demonstrated a surprising correlation between modafinil and neuroprotection (Han, Chen, Liu, & Zhu, 2018). This compound decreases the fatigue in stroke survivors (Bivard et al, 2017). It was reported that the intraperitoneal (i.p.)…”