{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:48:17Z","timestamp":1760986097284},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"bial"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Optimisation of dopaminergic therapy may alleviate fluctuation-related pain in Parkinson\u2019s disease (PD). Opicapone (OPC) is a third-generation, once-daily catechol-O-methyltransferase inhibitor shown to be generally well tolerated and efficacious in reducing OFF-time in two pivotal trials in patients with PD and end-of-dose motor fluctuations. The OpiCapone Effect on motor fluctuations and pAiN (OCEAN) trial aims to investigate the efficacy of OPC 50\u2009mg in PD patients with end-of-dose motor fluctuations and associated pain, when administered as adjunctive therapy to existing treatment with levodopa\/dopa decarboxylase inhibitor (DDCi).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>OCEAN is a Phase IV, international, multicentre, randomised, double-blind, placebo-controlled, parallel-group, interventional trial in PD patients with end-of-dose motor fluctuations and associated pain. It consists of a 1-week screening period, 24-week double-blind treatment period and 2-week follow-up period. Eligible patients will be randomised 1:1 to OPC 50\u2009mg or placebo once daily while continuing current treatment with levodopa\/DDCi and other chronic, stable anti-PD and\/or analgesic treatments. The primary efficacy endpoint is change from baseline in Domain 3 (fluctuation-related pain) of the King\u2019s Parkinson\u2019s disease Pain Scale (KPPS). The key secondary efficacy endpoint is change from baseline in Domain B (anxiety) of the Movement Disorder Society-sponsored Non-Motor rating Scale (MDS-NMS). Additional secondary efficacy assessments include other domains and total scores of the KPPS and MDS-NMS, the Parkinson\u2019s Disease Questionnaire (PDQ-8), the MDS-sponsored Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) Parts III and IV, Clinical and Patient\u2019s Global Impressions of Change, and change in functional status via Hauser\u2019s diary. Safety assessments include the incidence of treatment-emergent adverse events. The study will be conducted in approximately 140 patients from 50 clinical sites in Germany, Italy, Portugal, Spain and the United Kingdom. Recruitment started in February 2021 and the last patient is expected to complete the study by late 2022.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>The OCEAN trial will help determine whether the use of adjunctive OPC 50\u2009mg treatment can improve fluctuation-associated pain in PD patients with end-of-dose motor fluctuations. The robust design of OCEAN will address the current lack of reliable evidence for dopaminergic-based therapy in the treatment of PD-associated pain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>EudraCT number <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\">2020\u2013001175-32<\/jats:ext-link>; registered on 2020-08-07.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-022-02602-8","type":"journal-article","created":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T10:02:58Z","timestamp":1647079378000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Opicapone versus placebo in the treatment of Parkinson\u2019s disease patients with end-of-dose motor fluctuation-associated pain: rationale and design of the randomised, double-blind OCEAN (OpiCapone Effect on motor fluctuations and pAiN) trial"],"prefix":"10.1186","volume":"22","author":[{"given":"K. Ray","family":"Chaudhuri","sequence":"first","affiliation":[]},{"given":"Per","family":"Odin","sequence":"additional","affiliation":[]},{"given":"Joaquim J.","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Angelo","family":"Antonini","sequence":"additional","affiliation":[]},{"given":"Olivier","family":"Rascol","sequence":"additional","affiliation":[]},{"given":"M\u00f3nica M.","family":"Kurtis","sequence":"additional","affiliation":[]},{"given":"Alexander","family":"Storch","sequence":"additional","affiliation":[]},{"given":"Kirsty","family":"Bannister","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcio","family":"Soares-da-Silva","sequence":"additional","affiliation":[]},{"given":"Raquel","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Diogo","family":"Magalh\u00e3es","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Francisco","family":"Rocha","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"2602_CR1","volume-title":"An essay on the shaking palsy","author":"J Parkinson","year":"1817","unstructured":"Parkinson J. An essay on the shaking palsy. London: Sherwood, Neely, and Jones; 1817."},{"issue":"Suppl","key":"2602_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1136\/jnnp.52.suppl.11","volume":"Suppl","author":"G Stern","year":"1989","unstructured":"Stern G. Did parkinsonism occur before 1817? J Neurol Neurosurg Psychiatry. 1989;Suppl(Suppl):11\u20132. https:\/\/doi.org\/10.1136\/jnnp.52.suppl.11.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2602_CR3","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.parkreldis.2009.11.006","volume":"16","author":"D Bereczki","year":"2010","unstructured":"Bereczki D. The description of all four cardinal signs of Parkinson's disease in a Hungarian medical text published in 1690. Parkinsonism Relat Disord. 2010;16:290\u20133. https:\/\/doi.org\/10.1016\/j.parkreldis.2009.11.006.","journal-title":"Parkinsonism Relat Disord"},{"key":"2602_CR4","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/mds.27386","volume":"33","author":"K Ray Chaudhuri","year":"2018","unstructured":"Ray Chaudhuri K, Poewe W, Brooks D. Motor and nonmotor complications of levodopa: phenomenology, risk factors, and imaging features. Mov Disord. 2018;33:909\u201319. https:\/\/doi.org\/10.1002\/mds.27386.","journal-title":"Mov Disord"},{"key":"2602_CR5","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1212\/WNL.0b013e318285c0ed","volume":"80","author":"A Storch","year":"2013","unstructured":"Storch A, Schneider CB, Wolz M, St\u00fcrwald Y, Nebe A, Odin P, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology. 2013;80:800\u20139. https:\/\/doi.org\/10.1212\/WNL.0b013e318285c0ed.","journal-title":"Neurology."},{"key":"2602_CR6","doi-asserted-by":"publisher","first-page":"292719","DOI":"10.4061\/2011\/292719","volume":"2011","author":"G Kleiner-Fisman","year":"2011","unstructured":"Kleiner-Fisman G, Martine R, Lang AE, Stern MB. Development of a non-motor fluctuation assessment instrument for Parkinson disease. Parkinsons Dis. 2011;2011:292719. https:\/\/doi.org\/10.4061\/2011\/292719.","journal-title":"Parkinsons Dis"},{"key":"2602_CR7","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.clineuro.2014.10.006","volume":"127","author":"L Brun","year":"2014","unstructured":"Brun L, Lefaucheur R, Fetter D, Derrey S, Borden A, Wallon D, et al. Non-motor fluctuations in Parkinson's disease: prevalence, characteristics and management in a large cohort of parkinsonian outpatients. Clin Neurol Neurosurg. 2014;127:93\u20136. https:\/\/doi.org\/10.1016\/j.clineuro.2014.10.006.","journal-title":"Clin Neurol Neurosurg"},{"key":"2602_CR8","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1002\/mds.26731","volume":"31","author":"R Mart\u00ednez-Fern\u00e1ndez","year":"2016","unstructured":"Mart\u00ednez-Fern\u00e1ndez R, Schmitt E, Martinez-Martin P, Krack P. The hidden sister of motor fluctuations in Parkinson's disease: a review on nonmotor fluctuations. Mov Disord. 2016;31:1080\u201394. https:\/\/doi.org\/10.1002\/mds.26731.","journal-title":"Mov Disord"},{"key":"2602_CR9","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1136\/jnnp.2006.098327","volume":"78","author":"D Grosset","year":"2007","unstructured":"Grosset D, Taurah L, Burn DJ, MacMahon D, Forbes A, Turner K, et al. A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis. J Neurol Neurosurg Psychiatry. 2007;78:465\u20139. https:\/\/doi.org\/10.1136\/jnnp.2006.098327.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2602_CR10","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1007\/s00415-012-6557-8","volume":"259","author":"A Antonini","year":"2012","unstructured":"Antonini A, Barone P, Marconi R, Morgante L, Zappulla S, Pontieri FE, et al. The progression of non-motor symptoms in Parkinson's disease and their contribution to motor disability and quality of life. J Neurol. 2012;259:2621\u201331. https:\/\/doi.org\/10.1007\/s00415-012-6557-8.","journal-title":"J Neurol"},{"key":"2602_CR11","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1002\/mds.22142","volume":"23","author":"L N\u00e8gre-Pag\u00e8s","year":"2008","unstructured":"N\u00e8gre-Pag\u00e8s L, Regragui W, Bouhassira D, Grandjean H, Rascol O. DoPaMiP study group. Chronic pain in Parkinson's disease: the cross-sectional French DoPaMiP survey. Mov Disord. 2008;23:1361\u20139. https:\/\/doi.org\/10.1002\/mds.22142.","journal-title":"Mov Disord"},{"key":"2602_CR12","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1111\/ene.13624","volume":"25","author":"A Antonini","year":"2018","unstructured":"Antonini A, Tinazzi M, Abbruzzese G, Berardelli A, Chaudhuri KR, Defazio G, et al. Pain in Parkinson's disease: facts and uncertainties. Eur J Neurol. 2018;25:917\u2013e69. https:\/\/doi.org\/10.1111\/ene.13624.","journal-title":"Eur J Neurol"},{"key":"2602_CR13","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s12325-018-0687-z","volume":"35","author":"C Cattaneo","year":"2018","unstructured":"Cattaneo C, Kulisevsky J, Tubazio V, Castellani P. Long-term efficacy of safinamide on Parkinson's disease chronic pain. Adv Ther. 2018;35:515\u201322. https:\/\/doi.org\/10.1007\/s12325-018-0687-z.","journal-title":"Adv Ther"},{"issue":"Suppl 1","key":"2602_CR14","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.3233\/JPD-202069","volume":"10","author":"C Buhmann","year":"2020","unstructured":"Buhmann C, Kassubek J, Jost WH. Management of pain in Parkinson's disease. J Parkinsons Dis. 2020;10(Suppl 1):S37\u201348. https:\/\/doi.org\/10.3233\/JPD-202069.","journal-title":"J Parkinsons Dis"},{"key":"2602_CR15","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.neurol.2020.06.015","volume":"177","author":"A Marques","year":"2021","unstructured":"Marques A, Brefel-Courbon C. Chronic pain in Parkinson's disease: clinical and pathophysiological aspects. Rev Neurol (Paris). 2021;177:394\u20139. https:\/\/doi.org\/10.1016\/j.neurol.2020.06.015.","journal-title":"Rev Neurol (Paris)"},{"key":"2602_CR16","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.3233\/JPD-202088","volume":"10","author":"P Ghosh","year":"2020","unstructured":"Ghosh P, Imbriani P, Caputi N, Natoli S, Schirinzi T, Di Lazzaro G, et al. A dual Centre study of pain in Parkinson's disease and its relationship with other non-motor symptoms. J Parkinsons Dis. 2020;10:1817\u201325. https:\/\/doi.org\/10.3233\/JPD-202088.","journal-title":"J Parkinsons Dis"},{"key":"2602_CR17","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1002\/mds.26826","volume":"31","author":"A Polli","year":"2016","unstructured":"Polli A, Weis L, Biundo R, Thacker M, Turolla A, Koutsikos K, et al. Anatomical and functional correlates of persistent pain in Parkinson's disease. Mov Disord. 2016;31:1854\u201364. https:\/\/doi.org\/10.1002\/mds.26826.","journal-title":"Mov Disord"},{"issue":"Suppl 1","key":"2602_CR18","doi-asserted-by":"publisher","first-page":"S98","DOI":"10.1002\/mds.22716","volume":"25","author":"B Ford","year":"2010","unstructured":"Ford B. Pain in Parkinson's disease. Mov Disord. 2010;25(Suppl 1):S98\u2013103. https:\/\/doi.org\/10.1002\/mds.22716.","journal-title":"Mov Disord"},{"key":"2602_CR19","doi-asserted-by":"publisher","first-page":"e0136541","DOI":"10.1371\/journal.pone.0136541","volume":"10","author":"P Valkovic","year":"2015","unstructured":"Valkovic P, Minar M, Singliarova H, Harsany J, Hanakova M, Martinkova J, et al. Pain in Parkinson's disease: a cross-sectional study of its prevalence, types, and relationship to depression and quality of life. PLoS One. 2015;10:e0136541. https:\/\/doi.org\/10.1371\/journal.pone.0136541.","journal-title":"PLoS One"},{"key":"2602_CR20","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3390\/neurolint12030014","volume":"12","author":"A Edinoff","year":"2020","unstructured":"Edinoff A, Sathivadivel N, McBride T, Parker A, Okeagu C, Kaye AD, et al. Chronic pain treatment strategies in Parkinson's disease. Neurol Int. 2020;12:61\u201376. https:\/\/doi.org\/10.3390\/neurolint12030014.","journal-title":"Neurol Int"},{"key":"2602_CR21","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.parkreldis.2013.02.003","volume":"19","author":"C Brefel-Courbon","year":"2013","unstructured":"Brefel-Courbon C, Ory-Magne F, Thalamas C, Payoux P, Rascol O. Nociceptive brain activation in patients with neuropathic pain related to Parkinson's disease. Parkinsonism Relat Disord. 2013;19:548\u201352. https:\/\/doi.org\/10.1016\/j.parkreldis.2013.02.003.","journal-title":"Parkinsonism Relat Disord"},{"key":"2602_CR22","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1097\/WCO.0000000000000711","volume":"32","author":"K Rukavina","year":"2019","unstructured":"Rukavina K, Leta V, Sportelli C, Buhidma Y, Duty S, Malcangio M, et al. Pain in Parkinson's disease: new concepts in pathogenesis and treatment. Curr Opin Neurol. 2019;32:579\u201388. https:\/\/doi.org\/10.1097\/WCO.0000000000000711.","journal-title":"Curr Opin Neurol"},{"key":"2602_CR23","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1007\/s00415-012-6754-5","volume":"260","author":"A Truini","year":"2013","unstructured":"Truini A, Frontoni M, Cruccu G. Parkinson's disease related pain: a review of recent findings. J Neurol. 2013;260:330\u20134. https:\/\/doi.org\/10.1007\/s00415-012-6754-5.","journal-title":"J Neurol"},{"key":"2602_CR24","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1097\/SPC.0000000000000546","volume":"15","author":"K Rukavina","year":"2021","unstructured":"Rukavina K, Cummins TM, Ray CK, Kirtsy B. Pain in Parkinson's disease: mechanism-based treatment strategies. Curr Opin Support Palliat Care. 2021;15:108\u201315. https:\/\/doi.org\/10.1097\/SPC.0000000000000546.","journal-title":"Curr Opin Support Palliat Care"},{"key":"2602_CR25","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1017\/cjn.2020.13","volume":"47","author":"V Karnik","year":"2020","unstructured":"Karnik V, Farcy N, Zamorano C, Bruno V. Current status of pain Management in Parkinson's disease. Can J Neurol Sci. 2020;47:336\u201343. https:\/\/doi.org\/10.1017\/cjn.2020.13.","journal-title":"Can J Neurol Sci"},{"key":"2602_CR26","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/mdc3.12469","volume":"4","author":"M Rodr\u00edguez-Violante","year":"2017","unstructured":"Rodr\u00edguez-Violante M, Alvarado-Bola\u00f1os A, Cervantes-Arriaga A, Martinez-Martin P, Rizos A, Chaudhuri KR. Clinical determinants of Parkinson's disease-associated pain using the King's Parkinson's disease pain scale. Mov Disord Clin Pract. 2017;4:545\u201351. https:\/\/doi.org\/10.1002\/mdc3.12469.","journal-title":"Mov Disord Clin Pract"},{"key":"2602_CR27","doi-asserted-by":"publisher","first-page":"7264","DOI":"10.1523\/JNEUROSCI.3862-14.2015","volume":"35","author":"E Navratilova","year":"2015","unstructured":"Navratilova E, Xie JY, Meske D, Qu C, Morimura K, Okun A, et al. Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain. J Neurosci. 2015;35:7264\u201371. https:\/\/doi.org\/10.1523\/JNEUROSCI.3862-14.2015.","journal-title":"J Neurosci"},{"key":"2602_CR28","doi-asserted-by":"publisher","first-page":"e89999","DOI":"10.1371\/journal.pone.0089999","volume":"9","author":"DL Garc\u00eda-Ram\u00edrez","year":"2014","unstructured":"Garc\u00eda-Ram\u00edrez DL, Calvo JR, Hochman S, Quevedo JN. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord. PLoS One. 2014;9:e89999. https:\/\/doi.org\/10.1371\/journal.pone.0089999.","journal-title":"PLoS One"},{"key":"2602_CR29","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1002\/mds.20629","volume":"20","author":"C Brefel-Courbon","year":"2005","unstructured":"Brefel-Courbon C, Payoux P, Thalamas C, Ory F, Quelven I, Chollet F, et al. Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord. 2005;20:1557\u201363. https:\/\/doi.org\/10.1002\/mds.20629.","journal-title":"Mov Disord"},{"key":"2602_CR30","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/mds.27602","volume":"34","author":"K Seppi","year":"2019","unstructured":"Seppi K, Chaudhuri KR, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, et al. The collaborators of the Parkinson's disease update on non-motor symptoms study group on behalf of the movement disorders society evidence-based medicine committee. Update on treatments for nonmotor symptoms of Parkinson's disease-an evidence-based medicine review. Mov Disord. 2019;34:180\u201398. https:\/\/doi.org\/10.1002\/mds.27602.","journal-title":"Mov Disord"},{"key":"2602_CR31","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/SPC.0000000000000207","volume":"10","author":"K Bannister","year":"2016","unstructured":"Bannister K, Dickenson AH. What do monoamines do in pain modulation? Curr Opin Support Palliat Care. 2016;10:143\u20138. https:\/\/doi.org\/10.1097\/SPC.0000000000000207.","journal-title":"Curr Opin Support Palliat Care"},{"key":"2602_CR32","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1001\/jamaneurol.2015.8","volume":"72","author":"YJ Jung","year":"2015","unstructured":"Jung YJ, Kim HJ, Jeon BS, Park H, Lee WW, Paek SH. An 8-year follow-up on the effect of subthalamic nucleus deep brain stimulation on pain in Parkinson disease. JAMA Neurol. 2015;72:504\u201310. https:\/\/doi.org\/10.1001\/jamaneurol.2015.8.","journal-title":"JAMA Neurol"},{"key":"2602_CR33","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/mds.27626","volume":"34","author":"HS Dafsari","year":"2019","unstructured":"Dafsari HS, Martinez-Martin P, Rizos A, Trost M, Dos Santos Ghilardi MG, Reddy P, et al. EUROPAR and the international Parkinson and movement disorders society non-motor Parkinson's disease study group. EuroInf 2: subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease. Mov Disord. 2019;34:353\u201365. https:\/\/doi.org\/10.1002\/mds.27626.","journal-title":"Mov Disord"},{"key":"2602_CR34","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/S1474-4422(15)00243-4","volume":"14","author":"C Trenkwalder","year":"2015","unstructured":"Trenkwalder C, Chaudhuri KR, Martinez-Martin P, Rascol O, Ehret R, Vali\u0161 M, et al. PANDA study group. Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2015;14:1161\u201370. https:\/\/doi.org\/10.1016\/S1474-4422(15)00243-4.","journal-title":"Lancet Neurol"},{"key":"2602_CR35","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1002\/mds.26270","volume":"30","author":"KR Chaudhuri","year":"2015","unstructured":"Chaudhuri KR, Rizos A, Trenkwalder C, Rascol O, Pal S, Martino D, et al. EUROPAR and the IPMDS non motor PD study group. King's Parkinson's disease pain scale, the first scale for pain in PD: an international validation. Mov Disord. 2015;30:1623\u201331. https:\/\/doi.org\/10.1002\/mds.26270.","journal-title":"Mov Disord"},{"key":"2602_CR36","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2147\/cia.s6456","volume":"5","author":"W Poewe","year":"2010","unstructured":"Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson's disease: an old drug still going strong. Clin Interv Aging. 2010;5:229\u201338. https:\/\/doi.org\/10.2147\/cia.s6456.","journal-title":"Clin Interv Aging"},{"key":"2602_CR37","doi-asserted-by":"publisher","first-page":"3396","DOI":"10.1021\/jm1001524","volume":"53","author":"LE Kiss","year":"2010","unstructured":"Kiss LE, Ferreira HS, Torr\u00e3o L, Bonif\u00e1cio MJ, Palma PN, Soares-da-Silva P, et al. Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase. J Med Chem. 2010;53:3396\u2013411. https:\/\/doi.org\/10.1021\/jm1001524.","journal-title":"J Med Chem"},{"key":"2602_CR38","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s40262-012-0024-7","volume":"52","author":"L Almeida","year":"2013","unstructured":"Almeida L, Rocha JF, Falc\u00e3o A, Palma PN, Loureiro AI, Pinto R, et al. Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor. Clin Pharmacokinet. 2013;52:139\u201351. https:\/\/doi.org\/10.1007\/s40262-012-0024-7.","journal-title":"Clin Pharmacokinet"},{"key":"2602_CR39","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.2169\/internalmedicine.56.7667","volume":"56","author":"S Ouma","year":"2017","unstructured":"Ouma S, Fukae J, Fujioka S, Yamamoto S, Hatano T, Yoritaka A, et al. The risk factors for the wearing-off phenomenon in Parkinson's disease in Japan: a cross-sectional, multicenter study. Intern Med. 2017;56:1961\u20136. https:\/\/doi.org\/10.2169\/internalmedicine.56.7667.","journal-title":"Intern Med"},{"key":"2602_CR40","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3346\/jkms.2009.24.2.311","volume":"24","author":"SM Cheon","year":"2009","unstructured":"Cheon SM, Park MJ, Kim WJ, Kim JW. Non-motor off symptoms in Parkinson's disease. J Korean Med Sci. 2009;24:311\u20134. https:\/\/doi.org\/10.3346\/jkms.2009.24.2.311.","journal-title":"J Korean Med Sci"},{"key":"2602_CR41","doi-asserted-by":"publisher","first-page":"116905","DOI":"10.1016\/j.jns.2020.116905","volume":"416","author":"S Sung","year":"2020","unstructured":"Sung S, Farrell M, Vijiaratnam N, Evans AH. Pain and dyskinesia in Parkinson's disease may share common pathophysiological mechanisms - an fMRI study. J Neurol Sci. 2020;416:116905. https:\/\/doi.org\/10.1016\/j.jns.2020.116905.","journal-title":"J Neurol Sci"},{"key":"2602_CR42","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.jns.2018.10.013","volume":"395","author":"S Sung","year":"2018","unstructured":"Sung S, Vijiaratnam N, Chan DWC, Farrell M, Evans AH. Parkinson disease: a systemic review of pain sensitivities and its association with clinical pain and response to dopaminergic stimulation. J Neurol Sci. 2018;395:172\u2013206. https:\/\/doi.org\/10.1016\/j.jns.2018.10.013.","journal-title":"J Neurol Sci"},{"key":"2602_CR43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s40265-014-0343-0","volume":"75","author":"T M\u00fcller","year":"2015","unstructured":"M\u00fcller T. Catechol-O-methyltransferase inhibitors in Parkinson's disease. Drugs. 2015;75:157\u201374. https:\/\/doi.org\/10.1007\/s40265-014-0343-0.","journal-title":"Drugs."},{"key":"2602_CR44","doi-asserted-by":"publisher","first-page":"513","DOI":"10.2174\/138920021705160324170558","volume":"17","author":"R Montioli","year":"2016","unstructured":"Montioli R, Voltattorni CB, Bertoldi M. Parkinson's disease: recent updates in the identification of human dopa decarboxylase inhibitors. Curr Drug Metab. 2016;17:513\u20138. https:\/\/doi.org\/10.2174\/138920021705160324170558.","journal-title":"Curr Drug Metab"},{"key":"2602_CR45","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1007\/s40265-016-0623-y","volume":"76","author":"LJ Scott","year":"2016","unstructured":"Scott LJ. Opicapone: a review in Parkinson's disease. Drugs. 2016;76:1293\u2013300. https:\/\/doi.org\/10.1007\/s40265-016-0623-y.","journal-title":"Drugs."},{"key":"2602_CR46","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1002\/mds.27475","volume":"33","author":"M Fabbri","year":"2018","unstructured":"Fabbri M, Ferreira JJ, Lees A, Stocchi F, Poewe W, Tolosa E, et al. Opicapone for the treatment of Parkinson's disease: a review of a new licensed medicine. Mov Disord. 2018;33:1528\u201339. https:\/\/doi.org\/10.1002\/mds.27475.","journal-title":"Mov Disord"},{"key":"2602_CR47","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/S1474-4422(15)00336-1","volume":"15","author":"JJ Ferreira","year":"2016","unstructured":"Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P. Bi-Park 1 investigators. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15:154\u201365. https:\/\/doi.org\/10.1016\/S1474-4422(15)00336-1.","journal-title":"Lancet Neurol"},{"key":"2602_CR48","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1001\/jamaneurol.2016.4703","volume":"74","author":"AJ Lees","year":"2017","unstructured":"Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, et al. BIPARK-2 study investigators. Opicapone as adjunct to levodopa therapy in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74:197\u2013206. https:\/\/doi.org\/10.1001\/jamaneurol.2016.4703.","journal-title":"JAMA Neurol"},{"key":"2602_CR49","unstructured":"Ongentys\u00ae Summary of Product Characteristics. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/ongentys-epar-product-information_en.pdf. Accessed 25 Nov 2021."},{"key":"2602_CR50","unstructured":"Ongentys\u00ae Highlights of Prescribing Information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/212489s000lbl.pdf. Accessed 25 Nov 2021."},{"issue":"Suppl 1","key":"2602_CR51","first-page":"191","volume":"22","author":"C Oliveira","year":"2015","unstructured":"Oliveira C, Lees A, Ferreira J, Lopes N, Costa R, Pinto R, et al. Evaluation of non-motor symptoms in opicapone treated Parkinson\u2019s disease patients: results from a double-blind, randomized, placebo-controlled study and open-label extension. Eur J Neurol. 2015;22(Suppl 1):191 abstract P1236.","journal-title":"Eur J Neurol"},{"key":"2602_CR52","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s40035-020-00187-1","volume":"9","author":"H Reichmann","year":"2020","unstructured":"Reichmann H, Lees A, Rocha JF, Magalh\u00e3es D, Soares-da-Silva P, OPTIPARK investigators. Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study. Transl Neurodegener. 2020;9:9. https:\/\/doi.org\/10.1186\/s40035-020-00187-1.","journal-title":"Transl Neurodegener"},{"key":"2602_CR53","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1002\/jcph.678","volume":"56","author":"O Rascol","year":"2016","unstructured":"Rascol O, Zesiewicz T, Chaudhuri KR, Asgharnejad M, Surmann E, Dohin E, et al. A randomized controlled exploratory pilot study to evaluate the effect of rotigotine transdermal patch on Parkinson's disease-associated chronic pain. J Clin Pharmacol. 2016;56:852\u201361. https:\/\/doi.org\/10.1002\/jcph.678.","journal-title":"J Clin Pharmacol"},{"key":"2602_CR54","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/mdc3.12728","volume":"6","author":"P Martinez-Martin","year":"2019","unstructured":"Martinez-Martin P, Schrag A, Weintraub D, Rizos A, Rodriguez-Blazquez C, Chaudhuri KR. IPMDS non motor PD study group. Pilot study of the International Parkinson and Movement Disorder Society-sponsored non-motor rating scale (MDS-NMS). Mov Disord Clin Pract. 2019;6:227\u201334. https:\/\/doi.org\/10.1002\/mdc3.12728.","journal-title":"Mov Disord Clin Pract"},{"key":"2602_CR55","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1002\/mds.27862","volume":"35","author":"KR Chaudhuri","year":"2020","unstructured":"Chaudhuri KR, Schrag A, Weintraub D, Rizos A, Rodriguez-Blazquez C, Mamikonyan E, et al. The movement disorder society nonmotor rating scale: initial validation study. Mov Disord. 2020;35:116\u201333. https:\/\/doi.org\/10.1002\/mds.27862.","journal-title":"Mov Disord"},{"key":"2602_CR56","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","volume":"23","author":"CG Goetz","year":"2008","unstructured":"Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society UPDRS revision task force. Movement Disorder Society-sponsored revision of the unified Parkinson's disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23:2129\u201370. https:\/\/doi.org\/10.1002\/mds.22340.","journal-title":"Mov Disord"},{"key":"2602_CR57","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1080\/08870449708406741","volume":"12","author":"C Jenkinson","year":"1997","unstructured":"Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, Hyman N. The PDQ-8: development and validation of a short-form Parkinson's disease questionnaire. Psychol Health. 1997;12:805\u201314. https:\/\/doi.org\/10.1080\/08870449708406741.","journal-title":"Psychol Health"},{"key":"2602_CR58","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S1474-4422(06)70373-8","volume":"5","author":"KR Chaudhuri","year":"2006","unstructured":"Chaudhuri KR, Healy DG, Schapira AH. National Institute for clinical excellence. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006;5:235\u201345. https:\/\/doi.org\/10.1016\/S1474-4422(06)70373-8.","journal-title":"Lancet Neurol"},{"key":"2602_CR59","doi-asserted-by":"publisher","unstructured":"Ozturk EA, Gundogdu I, Kocer B, Comoglu S, Cakci A. Chronic pain in Parkinson's disease: frequency, characteristics, independent factors, and relationship with health-related quality of life. J Back Musculoskelet Rehabil. 2016. https:\/\/doi.org\/10.3233\/BMR-160720.","DOI":"10.3233\/BMR-160720"},{"key":"2602_CR60","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jocn.2017.08.002","volume":"45","author":"SM Choi","year":"2017","unstructured":"Choi SM, Kim BC, Jung HJ, Yoon GJ, Kang KW, Choi KH, et al. Impact of pain and pain subtypes on the quality of life of patients with Parkinson's disease. J Clin Neurosci. 2017;45:105\u20139. https:\/\/doi.org\/10.1016\/j.jocn.2017.08.002.","journal-title":"J Clin Neurosci"},{"key":"2602_CR61","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.ejphar.2004.07.024","volume":"500","author":"N Hagelberg","year":"2004","unstructured":"Hagelberg N, J\u00e4\u00e4skel\u00e4inen SK, Martikainen IK, Mansikka H, Forssell H, Scheinin H, et al. Striatal dopamine D2 receptors in modulation of pain in humans: a review. Eur J Pharmacol. 2004;500:187\u201392. https:\/\/doi.org\/10.1016\/j.ejphar.2004.07.024.","journal-title":"Eur J Pharmacol"},{"issue":"Suppl 1","key":"2602_CR62","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1016\/j.parkreldis.2020.09.024","volume":"80","author":"PA LeWitt","year":"2020","unstructured":"LeWitt PA, Chaudhuri KR. Unmet needs in Parkinson disease: motor and non-motor. Parkinsonism Relat Disord. 2020;80(Suppl 1):S7\u2013S12. https:\/\/doi.org\/10.1016\/j.parkreldis.2020.09.024.","journal-title":"Parkinsonism Relat Disord"},{"key":"2602_CR63","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41531-019-0102-8","volume":"5","author":"GM Pontone","year":"2019","unstructured":"Pontone GM, Dissanayka N, Apostolova L, Brown RG, Dobkin R, Dujardin K, et al. Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson's disease. NPJ Parkinsons Dis. 2019;5:30. https:\/\/doi.org\/10.1038\/s41531-019-0102-8.","journal-title":"NPJ Parkinsons Dis"},{"key":"2602_CR64","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/mds.26125","volume":"30","author":"CC Aquino","year":"2015","unstructured":"Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord. 2015;30:80\u20139. https:\/\/doi.org\/10.1002\/mds.26125.","journal-title":"Mov Disord"},{"key":"2602_CR65","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/mds.21205","volume":"22","author":"J Kulisevsky","year":"2007","unstructured":"Kulisevsky J, Pascual-Sedano B, Barbanoj M, Gironell A, Pagonabarraga J, Garc\u00eda-S\u00e1nchez C. Acute effects of immediate and controlled-release levodopa on mood in Parkinson's disease: a double-blind study. Mov Disord. 2007;22:62\u20137. https:\/\/doi.org\/10.1002\/mds.21205.","journal-title":"Mov Disord"},{"key":"2602_CR66","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s1474-4422(02)00038-8","volume":"1","author":"R de la Fuente-Fern\u00e1ndez","year":"2002","unstructured":"de la Fuente-Fern\u00e1ndez R, Schulzer M, Stoessl AJ. The placebo effect in neurological disorders. Lancet Neurol. 2002;1:85\u201391. https:\/\/doi.org\/10.1016\/s1474-4422(02)00038-8.","journal-title":"Lancet Neurol"},{"key":"2602_CR67","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.neuron.2014.10.023","volume":"84","author":"F Benedetti","year":"2014","unstructured":"Benedetti F. Placebo effects: from the neurobiological paradigm to translational implications. Neuron. 2014;84:623\u201337. https:\/\/doi.org\/10.1016\/j.neuron.2014.10.023.","journal-title":"Neuron."},{"key":"2602_CR68","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1146\/annurev-pharmtox-010818-021542","volume":"59","author":"L Colloca","year":"2019","unstructured":"Colloca L. The placebo effect in pain therapies. Annu Rev Pharmacol Toxicol. 2019;59:191\u2013211. https:\/\/doi.org\/10.1146\/annurev-pharmtox-010818-021542.","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"2602_CR69","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/bs.irn.2020.03.031","volume":"153","author":"JS Lou","year":"2020","unstructured":"Lou JS. Placebo responses in Parkinson's disease. Int Rev Neurobiol. 2020;153:187\u2013211. https:\/\/doi.org\/10.1016\/bs.irn.2020.03.031.","journal-title":"Int Rev Neurobiol"},{"key":"2602_CR70","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/mds.25751","volume":"29","author":"R Borgohain","year":"2014","unstructured":"Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D, et al. Study 016 investigators. Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Mov Disord. 2014;29:229\u201337. https:\/\/doi.org\/10.1002\/mds.25751.","journal-title":"Mov Disord"},{"key":"2602_CR71","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.parkreldis.2020.04.012","volume":"75","author":"N Hattori","year":"2020","unstructured":"Hattori N, Tsuboi Y, Yamamoto A, Sasagawa Y, Nomoto M. ME2125-3 study group. Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: a randomized, double-blind, placebo-controlled, phase II\/III study. Parkinsonism Relat Disord. 2020;75:17\u201323. https:\/\/doi.org\/10.1016\/j.parkreldis.2020.04.012.","journal-title":"Parkinsonism Relat Disord"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-022-02602-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-022-02602-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-022-02602-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T10:03:07Z","timestamp":1647079387000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-022-02602-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,12]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["2602"],"URL":"https:\/\/doi.org\/10.1186\/s12883-022-02602-8","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,12]]},"assertion":[{"value":"8 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol was submitted to national Independent Ethics Committees and Competent Authorities and unconditional approval\/favourable opinion must be obtained before the start of the study. All patients must provide written informed consent in order to participate in the study. The study was submitted to and approved by the following Independent Ethics Committees: in Spain, CEIm Hospital Cl\u00ednic de Barcelona to cover all sites; in Portugal, Comiss\u00e3o de \u00c9tica para a Investiga\u00e7\u00e3o Cl\u00ednica to cover all sites; in the UK, London-Hampstead Research Ethics Committee and the Health Research Authority to cover all sites; in Germany, Ethikkommission bei der Medizinischen Fakult\u00e4t der LMU M\u00fcnchen, Ethik-Kommission des Landes Berlin, Ethik-Kommission der Bayerischen Landes\u00e4rztekammer, Ethikkommission der Fakult\u00e4t f\u00fcr Medizin der Technischen Universit\u00e4t M\u00fcnchen, Ethikkommission der Landes\u00e4rztekammer Th\u00fcringen, Universit\u00e4t Duisburg-Essen Ethik-Kommission and Ethik-Kommission bei der Landes\u00e4rztekammer Hessen; in Italy, Comitato Etico per la Sperimentazione Clinica della Provincia di Padova, Comitato Etico per la sperimentazione clinica della provincia di Venezia e IRCCS San Camillo, Comitato Etico referente Area Pavia- Direzione Scientifica Comitato Etico ASL Brindisi, Comitato Etico Interaziendale Novara, Comitato Etico Indipendente locale - AOU Consorziale Policlinico di Bari and Comitato Etico di Brescia Comitato Etico per la Ricerca Biomedica delle Province di Chieti e Pescara e dell\u2019Universit\u00e0 degli Studi \u201cG. D\u2019Annunzio\u201d di Chieti-Pescara.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KRC has participated in advisory boards for AbbVie, UCB, GKC, Bial, Cynapsus, Lobsor, STADA, Medtronic, Zambon, Profile, Sunovion, Roche, Theravance, Scion, Britannia, Acadia, and 4D; has received honoraria for lectures from AbbVie, Britannia, UCB, Zambon, Novartis, Boehringer Ingelheim, Bial, Kyowa Kirin, and SK Pharma; has received investigator-initiated grants from Britannia, AbbVie, UCB, GKC, and Bial; and has received academic grants from the EU, IMI EU, Horizon 2020, Parkinson\u2019s UK, National Institute for Health Research, Parkinson\u2019s Disease Non Motor Group, Kirby Laing Foundation, NPF, Medical Research Council, and Wellcome Trust.PO has received honoraria for advice and lectures for AbbVie, Bial, Britannia, Lobsor, Nordic Infucare and Zambon, and has received grants from AbbVie.JJF has provided consultancy for Ipsen, GlaxoSmithKline, Novartis, Teva, Lundbeck, Solvay, Abbott, BIAL, Merck-Serono and Merz; and has received grants from GlaxoSmithKline, Grunenthal, Teva and Funda\u00e7\u00e3o MSD.AA has received compensation for consultancy and speaker-related activities from UCB, Boehringer Ingelheim, Britannia, AbbVie, Zambon, Bial, NeuroDerm, Theravance Biopharma, Roche; he receives research support from Chiesi Pharmaceuticals, Lundbeck, Horizon 2020 - Grant 825785, Horizon 2020 - Grant 101016902, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation. He serves as consultant for Boehringer Ingelheim for legal cases on pathological gambling; owns Patent WO2015110261-A1; and owns shares in PD Neurotechnology Limited.OR has participated in advisory boards and\/or provided consultancy for AbbVie, Adamas, Acorda, Addex, AlzProtect, ApoPharma, AstraZeneca, Axovant, Bial, Biogen, Britannia, Buckwang, CereSpir, Clevexel, Denali, INC Research, IPMDS, Lundbeck, Lupin, Merck, MundiPharma, NeurATRIS, NeuroDerm, Novartis, ONO Pharma, Osmotica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Roche, Sanofi, Servier, Sunovion, Theranexus, Takeda, Teva, UCB, Vectura, Watermark Research, XenoPort, XO, Zambon; received grants from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJFox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020), Cure Parkinson\u2019s UK; and received a grant to participate in a symposium and contribute to the review of an article by the International Parkinson and Movement Disorder Society.MMK has received honoraria from AbbVie, Zambon, Bial and the International Parkinson and Movement Disorder Society.AS has received funding from the Deutsche Forschungsgemeinschaft (German Research Association) and the Helmholtz-Association, outside the submitted presented work. He has received honoraria for presentations\/advisory boards\/consultations from Desitin, Global Kinetics, Lobsor, STADA, Bial, RG Gesellschaft, and AbbVie, outside the submitted presented work. He has received royalties from Kohlhammer Verlag and Elsevier Press. He serves as an editorial board member of Stem Cells and Stem Cells International.KB has no competing interests.PSS is an employee of Bial \u2013 Portela & C\u00aa, S.A.RC is an employee of Bial \u2013 Portela & C\u00aa, S.A.DM is an employee of Bial \u2013 Portela & C\u00aa, S.A.JFR is an employee of Bial \u2013 Portela & C\u00aa, S.A.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"88"}}