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

Adrianus L.A.J. Hommel, Marjan J. Meinders, Nico J. Weerkamp, Carmen Richinger, Christian Schmotz, Stefan Lorenzl, Richard Dodel, Miguel Coelho, Joaquim J. Ferreira, Francois Tison, Thomas Boraud, Wassilios G. Meissner, Kristina Rosqvist, Jonathan Timpka, Per Odin, Michael Wittenberg, Bas R. Bloem, Raymond T. Koopmans, Anette Schragand,
JPD. 2020-07-28; 10(3): 1171-1184
DOI: 10.3233/JPD-202033

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Hommel ALAJ(1), Meinders MJ(2), Weerkamp NJ(3), Richinger C(4), Schmotz C(4), Lorenzl S(4), Dodel R(5), Coelho M(6), Ferreira JJ(6), Tison F(7), Boraud T(7), Meissner WG(7)(8), Rosqvist K(9), Timpka J(9), Odin P(9), Wittenberg M(10), Bloem BR(11), Koopmans RT(12), Schragand A(13); CLaSP consortium.

Author information:
(1)Radboud University Medical Center, Donders Institute for Brain, Cognition and
Behaviour, Department of Neurology, Nijmegen, The Netherlands; Groenhuysen
Organisation, Roosendaal, the Netherlands.
(2)Radboud University Medical Center, Radboud Institute for Health Sciences,
Scientici Center for Quality of Healthcare, Nijmegen, the Netherlands.
(3)Department of Neurology, Bronovo Medical Center, The Hague, The Netherlands.
(4)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.
(5)Department of Geriatric Medicine, University Hospital Essen, Essen, Germany.
(6)Instituto de Medicina Molecular Universidad di Lisboa, Lisbon, Portugal.
(7)Service de Neurologie, CHU de Bordeaux, Bordeaux, France and Univ. de
Bordeaux, Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Bordeaux,
(8)Department of Medicine, University of Otago, Christchurch, New Zealand and New
Zealand Brain Research Institute, Christchurch, New Zealand.
(9)Department of Clinical Sciences, Division of Neurology, Lund University, Lund,
(10)Coordinating Centre for Clinical Trials (KKS), Philipps-University Marburg,
Marburg, Germany.
(11)Radboud University Medical Center, Donders Institute for Brain, Cognition and
Behavior, Department of Neurology, Nijmegen, The Netherlands.
(12)Radboud University Medical Center, Department of Primary and Community Care,
Nijmegen, The Netherlands; Joachim en Anna, Center for Specialized Geriatric
Care, Nijmegen, The Netherlands.
(13)UCL Queen Square Institute of Neurology, University College London, Royal
Free Campus, Rowland Hill Street, London, UK.

BACKGROUND: Treatment of patients with late-stage parkinsonism is often

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.


Auteurs Bordeaux Neurocampus