Optimizing Treatment in Undertreated Late-Stage Parkinsonism: A Pragmatic Randomized Trial

Article type: Research Article

Authors: Hommel, Adrianus L.A.J.^a | Meinders, Marjan J.^b | Weerkamp, Nico J.^m | Richinger, Carmen^g | Schmotz, Christian^g | Lorenzl, Stefan^g | Dodel, Richard^h | Coelho, Miguel^j | Ferreira, Joaquim J.^j | Tison, Francois^e | Boraud, Thomas^e | Meissner, Wassilios G.^{e; f} | Rosqvist, Kristinaⁱ | Timpka, Jonathanⁱ | Odin, Perⁱ | Wittenberg, Michael^k | Bloem, Bas R.^l | Koopmans, Raymond T.^d | Schragand, Anette^{c; *} | the CLaSP consortium

Affiliations: [a] Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands; Groenhuysen Organisation, Roosendaal, the Netherlands | [b] Radboud University Medical Center, Radboud Institute for Health Sciences, Scientici Center for Quality of Healthcare, Nijmegen, the Netherlands | [c] UCL Queen Square Institute of Neurology, University College London, Royal Free Campus, Rowland Hill Street, London, UK | [d] Radboud University Medical Center, Department of Primary and Community Care, Nijmegen, The Netherlands; Joachim en Anna, Center for Specialized Geriatric Care, Nijmegen, The Netherlands | [e] Service de Neurologie, CHU de Bordeaux, Bordeaux, France and Univ. de Bordeaux, Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Bordeaux, France | [f] Department of Medicine, University of Otago, Christchurch, New Zealand and New Zealand Brain Research Institute, Christchurch, New Zealand | [g] Interdisziplinäres Zentrum für Palliativmedizin und Klinik für Neurologie Universität München – Klinikum Großhadern, Munich, Germany. Institute of Nursing Science and -Practice, Paracelsus Medical University Salzburg, Austria | [h] Department of Geriatric Medicine, University Hospital Essen, Essen, Germany | [i] Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden | [j] Instituto de Medicina Molecular Universidad di Lisboa, Lisbon, Portugal | [k] Coordinating Centre for Clinical Trials (KKS), Philipps-University Marburg, Marburg, Germany | [l] Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Neurology, Nijmegen, The Netherlands | [m] Department of Neurology, Bronovo Medical Center, The Hague, The Netherlands

Correspondence: [*] Correspondence to: Professor Anette Schrag, UCL Queen Square Institute of Neurology, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, London, UK. [email protected]

Abstract: Background:Treatment of patients with late-stage parkinsonism is often sub-optimal. Objective:To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. Methods:Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic a pragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living). Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function (UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, a per-protocol analysis was conducted. Results:Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations fully in 16 (28%) and partially in 21 (36%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference = –1.2, p = 0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference = –3.7, p = 0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group. Conclusions:The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize that specialist recommendations need to be accompanied by better strategies to implement these to further improve outcomes.

Keywords: Parkinsonian disorders, randomized controlled trial, treatment, activities of daily living, quality of life

DOI: 10.3233/JPD-202033

Journal: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1171-1184, 2020