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A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease
BACKGROUND: Apathy is highly prevalent and disabling in Parkinson's disease (PD). Pharmacological options for its management lack sufficient evidence. OBJECTIVE: We studied the effects of safinamide on apathy in PD. METHODS: Prospective, 24-week, two-site, randomized, double-blind, placebo-cont...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201638/ https://www.ncbi.nlm.nih.gov/pubmed/35720066 http://dx.doi.org/10.3389/fneur.2022.866502 |
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author | Kulisevsky, Jaime Martínez-Horta, Saul Campolongo, Antonia Pascual-Sedano, Berta Marín-Lahoz, Juan Bejr-kasem, Helena Aracil-Bolaños, Ignacio Horta-Barba, Andrea Puig-Davi, Arnau Pagonabarraga, Javier |
author_facet | Kulisevsky, Jaime Martínez-Horta, Saul Campolongo, Antonia Pascual-Sedano, Berta Marín-Lahoz, Juan Bejr-kasem, Helena Aracil-Bolaños, Ignacio Horta-Barba, Andrea Puig-Davi, Arnau Pagonabarraga, Javier |
author_sort | Kulisevsky, Jaime |
collection | PubMed |
description | BACKGROUND: Apathy is highly prevalent and disabling in Parkinson's disease (PD). Pharmacological options for its management lack sufficient evidence. OBJECTIVE: We studied the effects of safinamide on apathy in PD. METHODS: Prospective, 24-week, two-site, randomized, double-blind, placebo-controlled, parallel-group exploratory study in non-demented PD on stable dopaminergic therapy randomized 1:1 to adjunct safinamide (50 mg/day for 2 weeks and 100 mg/day for 22 weeks) or placebo. The primary endpoint was the mean change from baseline to week 24 on the Apathy Scale (AS) total score. Secondary endpoints included changes in cognition, activities of daily living, motor scores, the impression of change, and safety and tolerability measures. RESULTS: In total, 30 participants (active treatment = 15; placebo = 15; 80% showing clinically significant apathetic symptoms according to the AS) were enrolled, and included in the intention-to-treat analysis. Change in AS (ANOVA) showed a trend to significance [p = 0.059] mediated by a more marked decrease in AS score with safinamide (−7.5 ± 6.9) than with placebo (−2.8 ± 5.7). Post-hoc analysis (paired t-test) showed a significant positive change in the AS score between 12-week and 24-week [p = 0.001] only in the active group. No significant or trend changes were found for any of the secondary outcome variables. Adverse events were few and only mild in both treatment groups. CONCLUSIONS: Safinamide was safe and well-tolerated, but failed to provide evidence of improved apathy. The positive trend observed in the post-hoc analyses deserves to be studied in depth in larger studies. TRIAL REGISTRATION: EudraCT 2017-003254-17. |
format | Online Article Text |
id | pubmed-9201638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92016382022-06-17 A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease Kulisevsky, Jaime Martínez-Horta, Saul Campolongo, Antonia Pascual-Sedano, Berta Marín-Lahoz, Juan Bejr-kasem, Helena Aracil-Bolaños, Ignacio Horta-Barba, Andrea Puig-Davi, Arnau Pagonabarraga, Javier Front Neurol Neurology BACKGROUND: Apathy is highly prevalent and disabling in Parkinson's disease (PD). Pharmacological options for its management lack sufficient evidence. OBJECTIVE: We studied the effects of safinamide on apathy in PD. METHODS: Prospective, 24-week, two-site, randomized, double-blind, placebo-controlled, parallel-group exploratory study in non-demented PD on stable dopaminergic therapy randomized 1:1 to adjunct safinamide (50 mg/day for 2 weeks and 100 mg/day for 22 weeks) or placebo. The primary endpoint was the mean change from baseline to week 24 on the Apathy Scale (AS) total score. Secondary endpoints included changes in cognition, activities of daily living, motor scores, the impression of change, and safety and tolerability measures. RESULTS: In total, 30 participants (active treatment = 15; placebo = 15; 80% showing clinically significant apathetic symptoms according to the AS) were enrolled, and included in the intention-to-treat analysis. Change in AS (ANOVA) showed a trend to significance [p = 0.059] mediated by a more marked decrease in AS score with safinamide (−7.5 ± 6.9) than with placebo (−2.8 ± 5.7). Post-hoc analysis (paired t-test) showed a significant positive change in the AS score between 12-week and 24-week [p = 0.001] only in the active group. No significant or trend changes were found for any of the secondary outcome variables. Adverse events were few and only mild in both treatment groups. CONCLUSIONS: Safinamide was safe and well-tolerated, but failed to provide evidence of improved apathy. The positive trend observed in the post-hoc analyses deserves to be studied in depth in larger studies. TRIAL REGISTRATION: EudraCT 2017-003254-17. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201638/ /pubmed/35720066 http://dx.doi.org/10.3389/fneur.2022.866502 Text en Copyright © 2022 Kulisevsky, Martínez-Horta, Campolongo, Pascual-Sedano, Marín-Lahoz, Bejr-kasem, Aracil-Bolaños, Horta-Barba, Puig-Davi and Pagonabarraga. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Kulisevsky, Jaime Martínez-Horta, Saul Campolongo, Antonia Pascual-Sedano, Berta Marín-Lahoz, Juan Bejr-kasem, Helena Aracil-Bolaños, Ignacio Horta-Barba, Andrea Puig-Davi, Arnau Pagonabarraga, Javier A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease |
title | A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease |
title_full | A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease |
title_fullStr | A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease |
title_full_unstemmed | A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease |
title_short | A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson's Disease |
title_sort | randomized clinical trial to evaluate the effects of safinamide on apathetic non-demented patients with parkinson's disease |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201638/ https://www.ncbi.nlm.nih.gov/pubmed/35720066 http://dx.doi.org/10.3389/fneur.2022.866502 |
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