title: PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.
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.
authors.affiliation: Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany. georg.nuebling@med.uni-muenchen.de.|Department of Palliative Care, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany. georg.nuebling@med.uni-muenchen.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Nuebling
authors.affiliation: Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Hensler
authors.affiliation: Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany.|German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zwergal
authors.affiliation: Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Crispin
authors.affiliation: Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany.|Department of Palliative Care, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany.|Endowed Professorship for Interdisciplinary Research in Palliative Care, Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorenzl
mesh_terms: D000368:Aged; D019540:Area Under Curve; D003072:Cognition Disorders; D003863:Depression / Q000209:etiology; D018450:Disease Progression; D004311:Double-Blind Method; D004562:Electrocardiography; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D004856:Postural Balance / Q000187:drug effects; D012678:Sensation Disorders / Q000188:drug therapy / Q000209:etiology; D013494:Supranuclear Palsy, Progressive / Q000150:complications / Q000188:drug therapy*
chemical_list: D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline
keywords: Clinical trial; Progressive supranuclear palsy; Rasagiline; Tauopathy