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The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach

  • Neurology and Preclinical Neurological Studies - Original Article
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An Erratum to this article was published on 25 August 2016

Abstract

Formation of toxic α-synuclein oligomers appears to be a key underlying pathological mechanism of synucleinopathies such as Parkinson’s disease or multiple system atrophy (MSA). Given that Epigallocatechin-gallate has been shown to inhibit α-synuclein aggregation, it might represent a causal treatment option. Therefore, we set out to evaluate the safety, tolerability and a potential disease-modifying effect of Epigallocatechin-gallate in patients with MSA after 48 weeks of treatment. Power calculation was performed on existing natural history data on the progression of the Unified MSA Rating Scale as primary readout parameter. To assess the efficacy of Epigallocatechin-gallate versus placebo regarding the reduction of disease progression measured during the study period (80 % power, 5 % p level, 50 % effect size) 36 patients per group are needed. Considering a drop-out rate of 20 % a total of 86 patients will be recruited in this multicentre study. These data provide a solid rationale to investigate whether supplementation of Epigallocatechin-gallate can delay the progression of the MSA-related disability.

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Acknowledgments

We are thankful to all patients who decided to enroll in this study.

Funding

This study was funded by the ParkinsonFonds Deutschland gGmbH, deutsche Parkinson Vereinigung, Deutsche Stiftung Neurologie, Arthur Arnstein-Stiftung Berlin, Bischof Dr Karl Golser Stiftung, Lüneburg-Stiftung für Parkinsonforschung, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Standort München.

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    Authors and Affiliations

    1. Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany

      Johannes Levin, Madeleine Schuberth, Stefan Lorenzl & Kai Bötzel

    2. German Centre for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81377, Munich, Germany

      Johannes Levin, Sylvia Maaß, Gesine Respondek & Günter Höglinger

    3. Department of Neurology, Klinikum Rechts der Isar, Technical University, Munich, Germany

      Sylvia Maaß, Gesine Respondek & Günter Höglinger

    4. NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany

      Friedemann Paul

    5. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité University Medicine Berlin, Berlin, Germany

      Friedemann Paul

    6. Institute for Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-Universität, Munich, Germany

      Ullrich Mansmann

    7. Department of Neurology, Philipps Universität, Marburg, Germany

      Wolfgang H. Oertel

    8. Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria

      Stefan Lorenzl

    9. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

      Florian Krismer, Klaus Seppi, Werner Poewe & Gregor Wenning

    10. Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität, Munich, Germany

      Armin Giese

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    The PROMESA study group

    Corresponding author

    Correspondence to Johannes Levin.

    Additional information

    Johannes Levin, Sylvia Maaß, Madeleine Schuberth, Armin Giese. Kai Bötzel, and Günter Höglinger have contributed equally to this work.

    Appendix: PROMESA study group

    Appendix: PROMESA study group

    D. Berg, MD (Site PI, Universitätsklinikum Tübingen); J. Claßen, MD (Site PI, Universitätsklinikum Leipzig); G. Ebersbach, MD (Site PI, Kliniken Beelitz GmbH); K. Eggert, MD (Site PI, Universitätsklinikum Marburg); G. Höglinger, MD (Site PI, Universitätsklinikum München TU); J. Kassubek, MD (Site PI, Universitätsklinikum Ulm); J. Levin, MD (Site PI, Universitätsklinikum München LMU); A. Lipp, MD (Site PI, Universitätsklinikum Charité Berlin); M. Löhle, MD (Site PI, Universitätsklinikum Dresden); B. Mollenhauer, MD (Site PI, Paracelsus-Elena-Klinik Kassel); A. Münchau, MD (Site PI, Universitätsklinikum Schleswig-Holstein, Campus Lübeck); M. Südmeyer, MD (Site PI, Universitätsklinikum Düsseldorf); C. Blankenstein, MD (head of PROMESA-monitoring, MSZ, Universitätsklinikum München TU); C. Eberhardt (head of PROMESA-clinical supplies, Universitätsklinikum Charité Berlin); B. Ertl-Wagner, MD (head of PROMESA-neuroimaging, LMU München); A. Giese, MD (head of PROMESA-neuropathology, LMU München); H. Heise, PhD (head of PROMESA-project management, Universitätsklinikum München LMU); I. Ricard, PhD (head of PROMESA-data management, Universitätsklinikum München LMU); S. Zedler, PhD (head of PROMESA-safety management, Universitätsklinikum München LMU); K. Bötzel, MD, S. Lorenzl, MD, J. Schwarz, MD, F. Paul, MD, A. Gerbes, MD (PROMESA-data safety monitoring committee, Universitätsklinikum München LMU, Klinik Haag & Universitätsklinikum Charité Berlin).

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    Levin, J., Maaß, S., Schuberth, M. et al. The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach. J Neural Transm 123, 439–445 (2016). https://doi.org/10.1007/s00702-016-1507-8

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