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PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy

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Abstract

To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery–Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the “limb motor” subdomain, whereas performance appeared lower in the “mentation” and “history” subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

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Acknowledgments

The authors thank Carina Abright and Dr. Stefan Kammermeier for additional data collection as well as Dr. Siegbert Krafczyk (Klinikum der Universität München, Munich, Germany) for excellent technical assistance concerning posturographic measurements. This investigator-initiated trial was sponsored by TEVA pharmaceutics (Petah Tikva, Israel).

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Authors and Affiliations

  1. Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany

    Georg Nuebling, Mira Hensler, Sabine Paul, Andreas Zwergal & Stefan Lorenzl

  2. Department of Palliative Care, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany

    Georg Nuebling & Stefan Lorenzl

  3. German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Munich, Germany

    Andreas Zwergal

  4. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany

    Alexander Crispin

  5. Endowed Professorship for Interdisciplinary Research in Palliative Care, Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria

    Stefan Lorenzl

Authors
  1. Georg Nuebling
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  2. Mira Hensler
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  3. Sabine Paul
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  4. Andreas Zwergal
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  5. Alexander Crispin
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  6. Stefan Lorenzl
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Corresponding author

Correspondence to Georg Nuebling.

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Conflicts of interest

The authors declare that they have no conflict of interest. Prof. Stefan Lorenzl received honoraria from UCB, TEVA, Orion, Boehringer Ingelheim and Gruenenthal not related to this study. He serves as an advisory board member for UCB. The investigator-initiated trial presented here was sponsored by TEVA pharmaceutics (Petah Tikva, Israel). The decision to publish this article was solely the responsibility of the authors. All statements, opinions, and content presented in the published article are those of the authors and do not represent the opinions of Teva. Teva provided a medical accuracy review of the article.

Ethical standards

The study protocol, patient information and consent form were reviewed by an internal review board (application number 344-09). The trial was conducted according to international GCP standards (ICH guidelines and the Helsinki Declaration). Prior to inclusion, written informed consent was obtained from all participants or their caregivers, respectively. This trial was registered to clinicaltrials.gov (NCT01187888).

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Nuebling, G., Hensler, M., Paul, S. et al. PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy. J Neurol 263, 1565–1574 (2016). https://doi.org/10.1007/s00415-016-8169-1

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  • DOI: https://doi.org/10.1007/s00415-016-8169-1

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