Subclinical affective and cognitive fluctuations in Parkinson's disease: a randomized double-blind double-dummy study of Oral vs. Intrajejunal Levodopa
Por:
Kulisevsky, J, Bejr-Kasem, H, Martinez-Horta, S, Horta-Barba, A, Pascual-Sedano, B, Campolongo, A, Marin-Lahoz, J, Aracil-Bolanos, I, Perez-Perez, J, Izquierdo-Barrionuevo, C, de Fabregues, O, Puente, V, Crespo-Cuevas, A, Calopa, M, Pagonabarraga, J
Publicada:
1 nov 2020
Ahead of Print:
1 jun 2020
Resumen:
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.
Filiaciones:
Kulisevsky, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Bejr-Kasem, H:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Martinez-Horta, S:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Horta-Barba, A:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Pascual-Sedano, B:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Univ Oberta Catalunya UOC, Fac Hlth Sci, Barcelona, Spain
Campolongo, A:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Univ Oberta Catalunya UOC, Fac Hlth Sci, Barcelona, Spain
Marin-Lahoz, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Aracil-Bolanos, I:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Perez-Perez, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
Izquierdo-Barrionuevo, C:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
de Fabregues, O:
UAB, Neurodegenerat Dis Res Grp, Vall dHebron Univ Hosp, Movement Disorders Unit,Vall dHebron Res Inst,Neu, Barcelona, Spain
Puente, V:
UAB, Inst Municipal Invest Med, Neurol Dept, Hosp Mar, Barcelona, Spain
Crespo-Cuevas, A:
UAB, Dept Neurosci, Hosp Univ Germans Trias & Pujol, Barcelona, Spain
Calopa, M:
Hosp Univ Bellvitge, Neurol Serv, Barcelona, Spain
Pagonabarraga, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Univ Autonoma Barcelona UAB, Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Spain
|