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Subclinical affective and cognitive fluctuations in Parkinson's disease: a randomized double-blind double-dummy study of Oral vs. Intrajejunal Levodopa

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Abstract

Background

Chronic levodopa treatment in Parkinson’s disease (PD) may promote undesirable motor and non-motor fluctuations. Compared to chronic oral levodopa treatment, continuous infusion of levodopa/carbidopa intestinal gel (LCIG) in advanced PD reduces motor fluctuations. However, differences in their effect on acute non-motor changes were not formally demonstrated.

Objective

We performed a randomized, double-blind, double-dummy, crossover study to compare acute non-motor changes between intermittent oral immediate-release carbidopa/levodopa (LC-IR) and LCIG.

Methods

After > 12-h OFF, thirteen PD patients chronically treated with LCIG and without history of non-motor swings, were allocated to receive first, LCIG infusion plus three oral doses of placebo, or placebo infusion plus three oral doses of LC-IR. Over-encapsulated oral medication (LC-IR or placebo) was administered every 2 h. We monitored plasmatic levels of levodopa, motor status (UPDRS-III), mood, anxiety, and frontal functions at baseline (0-h) and hourly after each oral challenge.

Results

Repeated-measures ANOVAs showed significant group by treatment interaction indicating more fluctuations of levodopa plasma levels with LC-IR. No significant interactions were seen in the temporal profile of motor status, anxiety, mood and cognition. However, point-to-point parametric and nonparametric tests showed a significant more marked and more sustained improvement in anxiety scores under LCIG. A significant improvement of mood and verbal fluency was seen a + 3-h only under LCIG.

Discussion

Our sample of advanced PD patients exhibited moderate but significant non-motor fluctuations. LCIG was associated with a more favorable profile of acute affective and cognitive fluctuations that was particularly expressed at the first part of the infusion curve.

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Acknowledgements

We are grateful to all patients and caregivers for their generous participation in the study. This study was partially supported by FIS Grant PI15/00962; Rio Hortega CM17/00209 and CIBERNED (Instituto de Salud Carlos III, Spain); La Marató de TV3, Expedient 20142910, 2014/U/477, and an unrestrictive research grant from Abbvie.

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Authors and Affiliations

  1. Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, 08041, Barcelona, Spain

    Jaime Kulisevsky, Helena Bejr-Kasem, Saul Martinez-Horta, Andrea Horta-Barba, Berta Pascual-Sedano, Antonia Campolongo, Juan Marín-Lahoz, Ignacio Aracil-Bolaños, Jesús Pérez-Pérez, Cristina Izquierdo-Barrionuevo & Javier Pagonabarraga

  2. Institut d’Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Centro de Investigación en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

    Jaime Kulisevsky, Helena Bejr-Kasem, Saul Martinez-Horta, Andrea Horta-Barba, Berta Pascual-Sedano, Antonia Campolongo, Juan Marín-Lahoz, Ignacio Aracil-Bolaños, Jesús Pérez-Pérez, Cristina Izquierdo-Barrionuevo & Javier Pagonabarraga

  3. Faculty of Health Sciences, Universitat Oberta de Catalunya (UOC), Barcelona, Spain

    Berta Pascual-Sedano & Antonia Campolongo

  4. Movement Disorders Unit, Neurology Department, Vall d’Hebron University Hospital, Neurodegenerative Diseases Research Group-Vall d’Hebron Research Institute, UAB, Barcelona, Spain

    Oriol de Fàbregues

  5. Neurology Department, Institut Municipal d’Investigacio Medica, UAB, Hospital del Mar, Barcelona, Spain

    Victor Puente

  6. Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, UAB, Badalona, Barcelona, Spain

    Ane Crespo-Cuevas

  7. Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Spain

    Matilde Calopa

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  1. Jaime Kulisevsky
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  2. Helena Bejr-Kasem
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  3. Saul Martinez-Horta
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  14. Matilde Calopa
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  15. Javier Pagonabarraga
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Corresponding author

Correspondence to Jaime Kulisevsky.

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Conflicts of interest

J Kulisevsky received compensation for consultancy and speaker activities from UCB, AbbVie, Neuroderm, Teva, Roche and Zambon. He received research support from Teva, Zambon, Abbvie, Ciberned and Carlos III Institute Research Grant FIS PI18/0717; S Martinez-Horta received compensation for speaker activities from UCB, AbbVie and Roche. He received research support from the Huntington's Disease Society of America; H Bejr-kasem received compensation for speaker activities in scientific meetings supported by Zambon, and non-financial support for congress attendance from Abbvie, Zambon and Allergan.I Aracil-Bolaños has received research support from Carlos III Institute Research Grant CM19/00156 G; B Pascual-Sedano received compensation for consultancy from Ferrer and speaker activities from AbbVie, UCB and Teva; C Izquierdo received compensation for speaker activities from UCB and Abbvie; A Campolongo received compensation for consultancy and speaker activities from UCB, AbbVie and Teva; J Pagonabarraga has received honoraria as Speaker or as member of Advisory Board from Zambon, UCB, Abbvie, Allergan and Ipsen; J Marín received compensation for consultancy and speaker activities from UCB; J Perez-Perez, O de Fàbregues, V Puente, A Crespo-Cuevas and M Calopa have no conflict of interest to declare.

Ethical standard

The study has been approved by the ethical committee of sant Pau Hospital (Barcelona, Spain). Written informed consent was obtained from all participants and the study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Kulisevsky, J., Bejr-Kasem, H., Martinez-Horta, S. et al. Subclinical affective and cognitive fluctuations in Parkinson's disease: a randomized double-blind double-dummy study of Oral vs. Intrajejunal Levodopa. J Neurol 267, 3400–3410 (2020). https://doi.org/10.1007/s00415-020-10018-y

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  • DOI: https://doi.org/10.1007/s00415-020-10018-y

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