Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study
Thomas Foltynie,
Rachael Hunter,
Lynn Rochester,
Dilan Athauda,
Patricia Limousin,
Alexa King,
Simon Skene,
Kashfia Chowdhury,
Camille B Carroll,
Huw Morris,
Michele T Hu,
Monty Silverdale,
Rachel Gibson,
Marisa Chau,
Christine Lo,
Nirosen Vijiaratnam,
Christine Girges,
Grace Auld,
Kate Maclagan,
Steve Hibbert,
Gordon W Duncan,
Ray Chaudhuri,
Silvia Del Din,
Alison J Yarnall,
John Dickson,
Vincenzo Libri
Affiliations
Thomas Foltynie
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Rachael Hunter
Department of Primary Care and Population Health, University College London Research, London, UK
Lynn Rochester
NIHR Newcastle Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
Dilan Athauda
1 Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK
Patricia Limousin
UCL Functional Neurosurgery, National Hospital for Neurology and Neurosurgery, London, UK
Alexa King
1 Marchand Institute for Minimally Invasive Surgery, Mesa, Arizona, USA
Simon Skene
Faculty of Arts and Human Sciences, Surrey Clinical Trials Unit, University of Surrey, Guildford, UK
Kashfia Chowdhury
The Comprehensive Clinical Trials Unit, UCL, London, UK
Camille B Carroll
University Hospitals Plymouth NHS Trust, Plymouth, UK
Huw Morris
Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London, UK
Michele T Hu
1 Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
Monty Silverdale
2 Department of Neurology and Neurosurgery, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, Greater Manchester, UK
Rachel Gibson
Global Health, GSK, Stevenage, Hertfordshire, UK
Marisa Chau
4National Trauma Research Institute, Central Clinical School, Monash University, Melbourne, Victoria, Australia
Christine Lo
Oxford Parkinsons Disease Centre, University of Oxford, Oxford, UK
Nirosen Vijiaratnam
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Christine Girges
National Hospital for Neurology and Neurosurgery, London, UK
Grace Auld
The Comprehensive Clinical Trials Unit, UCL, London, UK
Kate Maclagan
The Comprehensive Clinical Trials Unit, UCL, London, UK
Steve Hibbert
The Comprehensive Clinical Trials Unit, UCL, London, UK
Gordon W Duncan
Western General Hospital, NHS Lothian, Edinburgh, UK
Ray Chaudhuri
Leicester Royal Infirmary, Leicester, UK
Silvia Del Din
Brain and Movement Research Group, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
Alison J Yarnall
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
John Dickson
Department of Nuclear Medicine, University College London Hopsitals NHS Trust, London, UK
Vincenzo Libri
Leonard Wolfson Experimental Neurology Centre, National Hospital for Neurology & Neurosurgery, London, UK
Introduction Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysis This is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and dissemination This trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbers NCT04232969, ISRCTN14552789.
