Fampridine and Acetazolamide in EA2 and Related Familial EA: A Prospective Randomized Placebo-Controlled Trial.


Journal

Neurology. Clinical practice
ISSN: 2163-0402
Titre abrégé: Neurol Clin Pract
Pays: United States
ID NLM: 101577149

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 25 06 2020
accepted: 22 10 2020
entrez: 6 9 2021
pubmed: 7 9 2021
medline: 7 9 2021
Statut: ppublish

Résumé

To determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2 (EA2), patients with EA2 were treated with a random sequence of fampridine, acetazolamide, and placebo in a 3-period crossover trial. A total of 30 patients with EA2 (8 female; aged 20-71 years; 18 genetically confirmed, 4 with a positive family history, 8 with the clinical diagnosis) were enrolled in this phase III, randomized, double-blind, placebo-controlled, 3-period crossover trial. Each period lasted 12 weeks with a 4-week washout period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary end point was the number of attacks during the last 30 days within the 12-week treatment period. Participants, caregivers, and those assessing the outcomes were blinded to the intervention. Compared with placebo, fampridine reduced the number of attacks to 63% (95% CI 54%-74%) and acetazolamide to 52% (95% CI 46%-60%). A total of 39 (26.5%) adverse events were observed under treatment with fampridine (mostly tingling paresthesia and fatigue), 66 (44.9%) happened under acetazolamide (mostly taste disturbance and gastrointestinal complaints), and 42 (28.6%) under placebo (mostly gastrointestinal complaints). Both fampridine and acetazolamide significantly reduce the number of attacks in patients with EA2 and related EA in comparison to placebo. Fampridine 10 mg twice daily had fewer side effects than acetazolamide 250 mg 3 times daily. The trial was registered with DRKS.de (DRKS00005258) and EudraCT (2013-000107-17). This study was supported by the Federal Ministry of Education and Research (BMBF) (grant number 01EO0901). Fampridine (study medication) was provided by Biogen Idec. Class II evidence.

Identifiants

pubmed: 34484942
doi: 10.1212/CPJ.0000000000001017
pii: NEURCLINPRACT2020056713
pmc: PMC8382428
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e438-e446

Informations de copyright

© 2021 American Academy of Neurology.

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Auteurs

Carolin Muth (C)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Julian Teufel (J)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Ludger Schöls (L)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Matthis Synofzik (M)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Christiana Franke (C)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Dagmar Timmann (D)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Ulrich Mansmann (U)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Michael Strupp (M)

Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ) (CM, JT, M. Strupp), Ludwig Maximilians University, Munich, LMU University Hospital, Campus Grosshadern; Department of Neurology and Hertie-Institute for Clinical Brain Research (LS, M. Synofzik), Eberhard Karls University and German Center for Neurodegenerative Diseases (DZNE), Tübingen; Department of Neurology (CF), Charité-Universitätsmedizin Berlin, Berlin, Germany, Formerly Department of Neurology, University of Dresden; Department of Neurology (DT), Essen University Hospital, University of Duisburg-Essen; and Department of Medical Information Sciences (UM), Biometry, and Epidemiology (IBE), Ludwig Maximilian University, Munich, Germany.

Classifications MeSH