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

Philippe Damier¹, Bertrand Degos², Giovanni Castelonovo³, Mathieu Anheim⁴, Isabelle Benatru⁵, Nicolas Carrière⁶, Olivier Colin⁷, Luc Defebvre⁶, Marie Deverdal³, Alexandre Eusebio⁸, Vanessa Ferrier⁹, Caroline Giordana⁹, Jean-Luc Houeto¹⁰, Severine Le Dily¹, Marie Mongin², Claire Thiriez¹¹, Christine Tranchant⁴, Denis Ravel¹², Jean-Christophe Corvol¹³, Olivier Rascol¹⁴, Yehezkel Ben Ari¹²

Affiliations

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.

PMID: 38291616
DOI: 10.1002/mds.29726

Randomized Controlled Trial

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

Philippe Damier et al. Mov Disord. 2024 Mar.

. 2024 Mar;39(3):618-622.

doi: 10.1002/mds.29726. Epub 2024 Jan 30.

Authors

Affiliations

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.

PMID: 38291616
DOI: 10.1002/mds.29726

Abstract

Background: Acting 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).

Objective: The objective of this study was to assess the efficacy of bumetanide, an Na-K-Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD.

Methods: This 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.

Results: Compared 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.

Conclusions: There 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.

Keywords: GABAergic cells; NKCC1 inhibitor; Parkinson's disease; bumetanide.

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References

1. Dorsey ER, Bloem BR. The Parkinson pandemic—a call to action. JAMA Neurol 2018;75(1):9–10. https://doi.org/10.1001/jamaneurol.2017.3299
1. Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386(9996):896–912. https://doi.org/10.1016/S0140-6736(14)61393-3
1. Lozovaya N, Eftekhari S, Cloarec R, et al. GABAergic inhibition in dual‐transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease. Nat Commun 2018;9(1):1422. https://doi.org/10.1038/s41467-018-03802-y
1. Pieraut S, Laurent‐Matha V, Sar C, et al. NKCC1 phosphorylation stimulates neurite growth of injured adult sensory neurons. J Neurosci 2007;27(25):6751–6759. https://doi.org/10.1523/JNEUROSCI.1337-07.2007
1. Nardou R, Ben‐Ari Y, Khalilov I. Bumetanide, an NKCC1 antagonist, does not prevent formation of epileptogenic focus but blocks epileptic focus seizures in immature rat hippocampus. J Neurophysiol 2009;101(6):2878–2888. https://doi.org/10.1152/jn.90761.2008

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

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

Authors

Affiliations

Abstract

References

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MeSH terms

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Grants and funding

LinkOut - more resources

Full Text Sources

Medical