A Double‐Blind, Randomized, Placebo‐Controlled Trial of Bumetanide in Parkinson's Disease

Author:

Damier Philippe1ORCID,Degos Bertrand2ORCID,Castelonovo Giovanni3,Anheim Mathieu4,Benatru Isabelle5,Carrière Nicolas6,Colin Olivier7,Defebvre Luc6,Deverdal Marie3,Eusebio Alexandre8,Ferrier Vanessa9,Giordana Caroline9,Houeto Jean‐Luc10,Le Dily Severine1,Mongin Marie2,Thiriez Claire11,Tranchant Christine4,Ravel Denis12,Corvol Jean‐Christophe13ORCID,Rascol Olivier14ORCID,Ben Ari Yehezkel12

Affiliation:

1. CIC1413 NS‐Park/FCRIN Network Nantes Université, CHU Nantes, INSERM Nantes France

2. Neurology Department, Avicenne Hospital NS‐Park/FCRIN Network INSERM U1050, CNRS UMR7241, Collège de France, Centre de Recherche Interdisciplinaire en Biologie (CIRB), Université PSL Sorbonne Paris Nord, APHP Paris France

3. NS‐Park/FCRIN Network CHU Nîmes Nîmes France

4. Department of Neurology, Strasbourg Federation of Translational Medicine (FMTS), Strasbourg INSERM, U964, CNRS, UMR7104 NS‐Park/FCRIN Network Strasbourg University, CHU Strasbourg Illkirch‐Graffenstaden France

5. Service de Neurologie, Centre Expert Parkinson INSERM, CIC 1402 NS‐Park/FCRIN Network CHU Poitiers Poitiers France

6. Neurology Department UMR 1172 NS‐Park/FCRIN Network Université Lille, CHU Lille, INSERM Lille France

7. Centre Expert Parkinson NS‐Park/FCRIN Network CH Brive‐la‐Gaillarde, CHU Limoges Brive‐la‐Gaillarde France

8. Department of Neurology NS‐Park/FCRIN Network Université Aix Marseille, AP‐HM Marseille France

9. Department of Neurology NS‐Park/FCRIN Network CHU Nice Nice France

10. Centre Expert Parkinson Limoges INSERM U1094 EpiMaCT NS‐Park/FCRIN Network CHU Limoges, Université de Limoges Limoges France

11. Department of Neurology NS‐Park/FCRIN Network CHU Caen Caen France

12. BA Therapeutics and Neurochlore Campus Scientifique de Luminy Marseille France

13. Department of Neurology, Pitié‐Salpêtrière Hospital Brain Institute‐ICM NS‐Park/FCRIN Network Assistance Publique‐Hôpitaux de Paris, INSERM, Sorbonne Université Paris France

14. Clinical Investigation Center CIC1436 Departments of Neurosciences and Clinical Pharmacology NS‐Park/FCRIN Network NeuroToul COEN Center University Hospital of Toulouse, INSERM, University of Toulouse 3 Toulouse France

Abstract

AbstractBackgroundActing on the main target of dopaminergic cells, the striatal γ‐aminobutyric acid (GABA)‐ergic cells, might be a new way to treat persons with Parkinson's disease (PD).ObjectiveThe objective of this study was to assess the efficacy of bumetanide, an Na–K–Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD.MethodsThis was a 4‐month double‐blind, randomized, parallel‐group, placebo‐controlled trial of 1.75 to 3 mg/day bumetanide as an adjunct to levodopa in 44 participants with PD and motor fluctuations.ResultsCompared to the baseline, the mean change in OFF Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score after 4 months of treatment (primary endpoint) did not improve significantly compared with placebo. No changes between participants treated with bumetanide and those treated with placebo were observed for most other outcome measures. Despite no relevant safety signals, bumetanide was poorly tolerated.ConclusionsThere was no evidence in this study that bumetanide has efficacy in improving motor symptoms of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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