Simvastatin as a neuroprotective treatment for Parkinson's disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study

Camille B. Carroll, Douglas Webb, Kara Nicola Stevens, Jane Vickery, Vicky Eyre, Susan Ball, Richard Wyse, Mike Webber, Andy Foggo, John Zajicek, Alan Whone, Siobhan Creanor

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative condition affecting approximately 185,000 people in the UK. No drug has been proven to slow disease progression. Epidemiological and pre-clinical data support simvastatin, a widely used cholesterol-lowering drug with a well-established safety profile, having neuroprotective properties. The aim of this study (Simvastatin as a neuroprotective treatment for PD (PD STAT)) is to determine whether simvastatin has the potential to slow PD progression. The study is part of the International Linked Clinical Trials initiative coordinated by The Cure Parkinson's Trust. This paper describes the protocol for the PD STAT study.

METHODS AND ANALYSIS: PD STAT is a double-blind, randomised, placebo-controlled, multi-centre, parallel group, futility trial in patients with PD of mild-moderate severity. 235 participants have been recruited and randomly allocated in a 1:1 ratio to receive either oral simvastatin or matched placebo. Treatment involves a 1-month low-dose phase (40 mg daily), followed by a 23-month high-dose phase (80 mg daily) and ends with a 2-month washout period. Participants are reviewed at clinic visits at 1 month, 6, 12, 18, 24 and 26 months post-baseline, with interim telephone follow-up to monitor for adverse events.The primary outcome is the change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III motor subscale score in the practically defined OFF medication state (OFF state) between baseline and 24 months. Primary analysis will be on a modified intention to treat basis and will include only those participants who progress to the high-dose phase of the study.


ETHICS AND DISSEMINATION: The protocol has been approved by the North East-Newcastle and North Tyneside 2 Research Ethics Committee. The results will be disseminated via research articles in peer-reviewed journals and presentations at local, national and international scientific meetings, as well as disseminated via patient groups, websites and networks. A summary of the study findings will be posted to participants at the end of the study.

TRIAL REGISTRATION: ISRCTN16108482 (prospectively registered); EudraCT 2015-000148-40; ClinicalTrials.gov NCT02787590; Pre-results.

Original languageEnglish
Article numbere029740
Number of pages11
JournalBMJ Open
Volume9
Issue number10
DOIs
Publication statusPublished - 7 Oct 2019

Keywords

  • MDS-UPDRS
  • Neuroprotective effect
  • Parkinson’s disease
  • Randomised controlled futility study
  • Statin

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