title: Rotigotine's effect on PLM-associated blood pressure elevations in restless legs syndrome: An RCT.
abstract: OBJECTIVE
  This double-blind, placebo-controlled, interventional trial was conducted to investigate the effects of rotigotine patch on periodic limb movement (PLM)-associated nocturnal systolic blood pressure (SBP) elevations.
  
  
  METHODS
  Patients with moderate to severe restless legs syndrome (RLS) were randomized to rotigotine (optimal dose [1-3 mg/24 h]) or placebo. Continuous beat-to-beat blood pressure (BP) assessments were performed during polysomnography at baseline and at the end of 4-week maintenance. Primary outcome was change in number of PLM-associated SBP elevations (defined as slope of linear regression ≥2.5 mm Hg/beat-to-beat interval over 5 consecutive heartbeats [≥10 mm Hg]). Additional outcomes were total SBP elevations, PLM-associated and total diastolic BP (DBP) elevations, periodic limb movements index (PLMI), and PLM in sleep arousal index (PLMSAI).
  
  
  RESULTS
  Of 81 randomized patients, 66 (37 rotigotine, 29 placebo) were included in efficacy assessments. PLM-associated SBP elevations were significantly reduced with rotigotine vs placebo (least squares mean treatment difference [95% confidence interval (CI)] -160.34 [-213.23 to -107.45]; p < 0.0001). Rotigotine-treated patients also had greater reduction vs placebo in total SBP elevations (-161.13 [-264.47 to -57.79]; p = 0.0028), PLM-associated elevations (-88.45 [-126.12 to -50.78]; p < 0.0001), and total DBP elevations (-93.81 [-168.45 to -19.16]; p = 0.0146), PLMI (-32.77 [-44.73 to -20.80]; p < 0.0001), and PLMSAI (-7.10 [-11.93 to -2.26]; p = 0.0047). Adverse events included nausea (rotigotine 23%; placebo 8%), headache (18% each), nasopharyngitis (18%; 8%), and fatigue (13%; 15%).
  
  
  CONCLUSIONS
  Further investigation is required to determine whether reductions in nocturnal BP elevations observed with rotigotine might modify cardiovascular risk.
  
  
  METHODS
  This study provides Class I evidence that for patients with moderate to severe RLS, rotigotine at optimal dose (1-3 mg/24 h) reduced PLM-associated nocturnal SBP elevations.
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany. axel.bauer@med.uni-muenchen.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Bauer
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Cassel
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Benes
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Kesper
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Rye
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Domenic
authors.initials: D
authors.lastname: Sica
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: John W
authors.initials: JW
authors.lastname: Winkelman
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Bauer
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Grieger
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Joeres
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Moran
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Schollmayer
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: John
authors.initials: J
authors.lastname: Whitesides
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Carney
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Walters
authors.affiliation: From the Munich University Clinic and DZHK (German Centre for Cardiovascular Research) (A.B.); Philipps Universität Marburg (W.C., K.K., W.O.); Somni Bene Institut für Medizinische Forschung und Schlafmedizin (H.B.), Schwerin; Medical Center (H.B.), Rostock University, Germany; Emory University (D.R.), Atlanta, GA; Virginia Commonwealth University (D.S.), Richmond; Massachusetts General Hospital (J.W.W.), Boston; UCB Pharma (L.B., F.G., L.J., E.S.), Monheim am Rhein, Germany; UCB Pharma (K.M.), Smyrna, GA; UCB Pharma (J.W.), Raleigh, NC; Evidence Scientific Solutions (H.C.C.), Horsham, UK; Vanderbilt University School of Medicine (A.S.W.), Nashville, TN; Hertie Foundation (W.O.), Frankfurt am Main; and Department of Neurosurgery (C.T.), University Medical Center, Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001795:Blood Pressure Determination; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016018:Least-Squares Analysis; D008875:Middle Aged; D020189:Nocturnal Myoclonus Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017440:Photoperiod; D017286:Polysomnography; D012148:Restless Legs Syndrome / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D012720:Severity of Illness Index; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D057968:Transdermal Patch / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine