title: Rotigotine in Hemodialysis-Associated Restless Legs Syndrome: A Randomized Controlled Trial.
abstract: BACKGROUND
  Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease.
  
  
  METHODS
  Double-blind placebo-controlled study.
  
  
  METHODS
  Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] ≥ 15) and Periodic Limb Movement Index (PLMI) ≥ 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe.
  
  
  METHODS
  Following randomization and titration (≤21 + 3 days) to optimal-dose rotigotine (1-3mg/24 h) or placebo, patients entered a 2-week maintenance period. Polysomnography was performed at baseline and the end of maintenance.
  
  
  METHODS
  Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score.
  
  
  RESULTS
  30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7±0.4 for rotigotine and 1.3±0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P=0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P=0.05] and -0.81 [95% CI, -1.94 to 0.33; P=0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (≥50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (≥2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0).
  
  
  CONCLUSIONS
  Small sample size and short duration.
  
  
  CONCLUSIONS
  Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients.
authors: Sleep Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INSERM U1061, Montpellier, France.
authors: Yves
authors: Y
authors: Dauvilliers
authors: Somni Bene Institut für Medizinische Forschung und Schlafmedizin, Schwerin, Germany; Rostock University, Medical Center, Rostock, Germany.
authors: Heike
authors: H
authors: Benes
authors: Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland.
authors: Markku
authors: M
authors: Partinen
authors: Helsinki University Central Hospital, Helsinki, Finland.
authors: Virpi
authors: V
authors: Rauta
authors: Sleep Medicine Centers of Western New York, West Seneca, NY.
authors: Daniel
authors: D
authors: Rifkin
authors: UCB Pharma, Brussels, Belgium.
authors: Elisabeth
authors: E
authors: Dohin
authors: UCB Pharma, Monheim am Rhein, Germany.
authors: Nadine
authors: N
authors: Goldammer
authors: UCB Pharma, Monheim am Rhein, Germany.
authors: Erwin
authors: E
authors: Schollmayer
authors: UCB Pharma, Monheim am Rhein, Germany.
authors: Hanna
authors: H
authors: Schröder
authors: Massachusetts General Hospital, Boston, MA. Electronic address: jwwinkelman@partners.org.
authors: John W
authors: JW
authors: Winkelman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000209:etiology*; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Chronic kidney disease (CKD); dopamine agonist; end-stage renal disease (ESRD); hemodialysis; periodic limb movement index (PLMI); periodic limb movements (PLM); randomized controlled trial (RCT); restless legs syndrome (RLS); rotigotine