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

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-est...

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Main Authors: Susan Ball, Douglas Webb, Camille B Carroll, Kara Nicola Stevens, Jane Vickery, Vicky Eyre, Richard Wyse, Mike Webber, Andy Foggo, John Zajicek, Alan Whone, Siobhan Creanor
Format: Article
Language:English
Published: BMJ Publishing Group 2019-10-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/10/e029740.full
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author Susan Ball
Douglas Webb
Camille B Carroll
Kara Nicola Stevens
Jane Vickery
Vicky Eyre
Richard Wyse
Mike Webber
Andy Foggo
John Zajicek
Alan Whone
Siobhan Creanor
author_facet Susan Ball
Douglas Webb
Camille B Carroll
Kara Nicola Stevens
Jane Vickery
Vicky Eyre
Richard Wyse
Mike Webber
Andy Foggo
John Zajicek
Alan Whone
Siobhan Creanor
author_sort Susan Ball
collection DOAJ
description 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.
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spelling doaj-art-bff309947e1443688e85e2f85179995e2024-12-14T07:40:09ZengBMJ Publishing GroupBMJ Open2044-60552019-10-0191010.1136/bmjopen-2019-029740Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility studySusan Ball0Douglas Webb1Camille B Carroll2Kara Nicola Stevens3Jane Vickery4Vicky Eyre5Richard Wyse6Mike Webber7Andy Foggo8John Zajicek9Alan Whone10Siobhan Creanor111 NIHR Applied Research Collaboration South West Peninsula (PenARC), Department of Health and Community Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK33 UNDP, Tblisi, GeorgiaUniversity Hospitals Plymouth NHS Trust, Plymouth, UKMedical Statistics Group, Faculty of Medicine and Dentistry, University of Plymouth, Plymouth, UK2 Peninsula Clinical Trials Unit, University of Plymouth, Plymouth, UK2 Peninsula Clinical Trials Unit, University of Plymouth, Plymouth, UK5 The Cure Parkinson`s Trust, London, UK6 PPI Representative, University of Plymouth, Plymouth, UK6 PPI Representative, University of Plymouth, Plymouth, UK7 School of Medicine, University of St Andrews, St Andrews, UK8 School of Translational Health Sciences, University of Bristol, Bristol, UKCentre for Health and Environmental Statistics, University of Plymouth, Plymouth, UKIntroduction 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.https://bmjopen.bmj.com/content/9/10/e029740.full
spellingShingle Susan Ball
Douglas Webb
Camille B Carroll
Kara Nicola Stevens
Jane Vickery
Vicky Eyre
Richard Wyse
Mike Webber
Andy Foggo
John Zajicek
Alan Whone
Siobhan Creanor
Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study
BMJ Open
title Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study
title_full Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study
title_fullStr Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study
title_full_unstemmed Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study
title_short Simvastatin as a neuroprotective treatment for Parkinson’s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study
title_sort simvastatin as a neuroprotective treatment for parkinson s disease pd stat protocol for a double blind randomised placebo controlled futility study
url https://bmjopen.bmj.com/content/9/10/e029740.full
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