title: Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study.
abstract: BACKGROUND
  The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed.
  
  
  METHODS
  To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson's Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson's Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks.
  
  
  CONCLUSIONS
  The LEAP-study will provide insights into the possible disease modifying effects of early levodopa.
  
  
  BACKGROUND
  ISRCTN30518857, EudraCT number 2011-000678-72.
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, PO BOX 22600, 1100 DD, Amsterdam, The Netherlands. c.v.verschuur@amc.uva.nl.
authors.forename: Constant V M
authors.initials: CV
authors.lastname: Verschuur
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, PO BOX 22600, 1100 DD, Amsterdam, The Netherlands. s.r.suwijn@amc.uva.nl.
authors.forename: S R
authors.initials: SR
authors.lastname: Suwijn
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands. Bart.Post@radboudumc.nl.
authors.forename: B
authors.initials: B
authors.lastname: Post
authors.affiliation: Academic Medical Center, Clinical Research Unit, Amsterdam, The Netherlands. m.g.dijkgraaf@amc.uva.nl.
authors.forename: M
authors.initials: M
authors.lastname: Dijkgraaf
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands. Bas.Bloem@radboudumc.nl.
authors.forename: B R
authors.initials: BR
authors.lastname: Bloem
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. J.J.van_Hilten@lumc.nl.
authors.forename: J J
authors.initials: JJ
authors.lastname: van Hilten
authors.affiliation: Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands. t.van.laar@umcg.nl.
authors.forename: T
authors.initials: T
authors.lastname: van Laar
authors.affiliation: Department of Neurology, Atrium-Orbis Medical Center Heerlen/Sittard, Heerlen, The Netherlands. g.tissingh@atriummc.nl.
authors.forename: G
authors.initials: G
authors.lastname: Tissingh
authors.affiliation: Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany. g.deuschl@neurologie.uni-kiel.de.
authors.forename: G
authors.initials: G
authors.lastname: Deuschl
authors.affiliation: The Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. lang@uhnresearch.ca.
authors.forename: A E
authors.initials: AE
authors.lastname: Lang
authors.affiliation: Academic Medical Center, Clinical Research Unit, Amsterdam, The Netherlands. r.j.dehaan@amc.uva.nl.
authors.forename: R J
authors.initials: RJ
authors.lastname: de Haan
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, PO BOX 22600, 1100 DD, Amsterdam, The Netherlands. r.m.debie@amc.uva.nl.
authors.forename: R M A
authors.initials: RM
authors.lastname: de Bie
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002230:Carbidopa / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D009426:Netherlands; D010300:Parkinson Disease / Q000188:drug therapy*; D011788:Quality of Life; D061665:Time-to-Treatment
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D007980:Levodopa; D002230:Carbidopa