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Exenatide Parkinsons Disease

17 October 2019

EXENATIDE-PD3 - A randomised, double blind, parallel group, placebo controlled Phase 3 trial of Exenatide once weekly over 2 years as a potential disease modifying treatment for Parkinson's disease

EudraCT: 2018-003028-35

 ISRCTN: TBC

exenatide
RECRUITMENT TARGET = 200 
ACTUAL RECRUITMENT = 0 (trial will start recruiting in November 2019)
Trial Information

Exenatide is a licensed, safe and effective treatment for patients with diabetes mellitus. Laboratory work has shown strong, reproducible evidence that this drug has beneficial "disease modifying" effects when given to animals with a range of experimental models of Parkinson's disease (PD). 

A pilot study in forty patients and a phase 2 trial with 60 patients with moderate symptoms of PD have already been completed. Half of the patients received Exenatide and half acted as controls. Those patients who received Exenatide had improved results in a number of assessments compared to the controls. 

This trial aims to confirm the initial results seen with Exenatide treatment in the pilot study. The trial will be a randomised, double-blind design. Two hundred patients with PD will be recruited and randomised to receive Exenatide or placebo injections once weekly. The drug/placebo will be given as a once weekly 2 milligrams injection under the skin in a similar way to one of the conventional "symptomatic" treatments for PD (Apomorphine). 

Detailed assessments will be made of all patients at baseline and periodically for a total of 96 weeks.

Aside from these assessments, all patients will continue their regular PD medications throughout the trial with adjustments made only according to clinical need. At 5 of the study visits participants will be asked not to take their medication for 8-36 hours prior to the visit. 

Who is organising and funding the research? 
This research is being funded by the National Institute Health Research Efficacy and Mechanism Evaluation (NIHR-EME) Programme (grant number 16/167/19). The trial is being co-ordinated by University College London Comprehensive Clinical Trials Unit. The doctors looking after you are not being paid for including you and have no conflicts of interest.

Participating centres / Research contacts
University College London Hospital c.girges@ucl.ac.uk
John Radcliffe Hospital, Oxford - Jessica.Welch@ouh.nhs.uk

Please contact the trial team for more information.

Information for Clinicians

Please find the eligibility criteria for EXENATIDE-PD3 below:

Participant Inclusion Criteria

  1. Diagnosis of Parkinson’s disease. Patients with clinical features indicating a diagnosis of Progressive Supranuclear Palsy, Multiple Systems Atrophy, Drug induced Parkinsonism, Dystonic tremor or Essential tremor will not be recruited.
  2. Hoehn and Yahr stage ≤2.5 in the ON medication state. This implies that all patients will be mobile without assistance during their best “ON” medication periods. 
  3. Between 25 and 80 years of age.
  4. On dopaminergic treatment for at least 4 weeks before enrolment. All participants must have had previous or ongoing exposure to dopaminergic treatment either as L-dopa or a dopamine agonist. If L-dopa has been stopped due to side effects or lack of response, the local PI should further confirm that the participant has clinical symptoms and signs and/or radiological investigations consistent with a diagnosis of Parkinson’s disease.
  5. Ability to self-administer, or to arrange carer administration of trial medication.
  6. Documented informed consent to participate.

Participant Exclusion Criteria

  1. Diagnosis or suspicion of other cause for Parkinsonism. Patients with clinical features indicating a diagnosis of Progressive Supranuclear Palsy, Multiple Systems Atrophy, Drug induced Parkinsonism, Dystonic tremor or Essential tremor will not be recruited.
  2. Patients unable to attend the clinic visits in the practically defined OFF medication state. 
  3. Body mass index <18.5. (Exenatide is known to cause weight loss therefore individuals that may not tolerate further weight loss will not be recruited).
  4. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
  5. Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.
  6. Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9)
  7. Prior intra-cerebral surgical intervention for Parkinson’s disease. Patients who have previously undergone Deep Brain Stimulation, intra-cerebral administration of growth factors, gene therapy or cell therapies will not be eligible.
  8. Previous participation in one of the following Parkinson’s disease trials (Biogen SPARK trial, Prothena Pasadena trial, Sanofi Genzyme MOVES-PD trial, UDCA-PD UP Study or any other trial still considered to involve a potentially PD modifying agent). In the event of any uncertainty, the Chief Investigator will discuss the relevance of exposure to any other specific trials/experimental agents with the local Principal Investigator before recruitment eligibility is confirmed.
  9. Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days.
  10. Previous exposure to exenatide.
  11. Impaired renal function with creatinine clearance <50ml/min.
  12. History of pancreatitis. Screening serum amylase value must fall within laboratory normal range +/- 50%.
  13. Type 1 or Type 2 Diabetes mellitus.
  14. Severe gastrointestinal disease (e.g. gastroparesis)
  15. Hyperlipidaemia. A lipid profile will be tested at the screening visit. Cholesterol or Triglyceride levels greater than 2 x the upper limit of normal will raise suspicion of a familial or acquired hyperlipidaemia and will prompt referral to a relevant specialist for investigation and treatment.
  16. History or family history of medullary thyroid cancer (MTC). Undiagnosed neck lump, hoarse voice or difficulty swallowing (not attributable to PD diagnosis).
  17. Multiple endocrine neoplasia 2 (MEN2) syndrome.
  18. Hypersensitivity to any of exenatide's excipients.
  19. Females that are pregnant or breast feeding. There are no safety data regarding exenatide use in pregnancy. 
  20. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire trial period and up to 3 months after the last dose of trial medication. Female participants who are able to become pregnant (defined as women of child bearing potential) will undergo a pregnancy test prior to randomisation and will be asked at each visit to confirm regular use of an effective method of contraception. 
  21. Participants who lack the capacity to give informed consent.
  22. Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator’s opinion compromises the potential participant’s ability to participate.
Meet the Team

Professor Thomas Foltynie
Exenatide-PD3 Chief Investigator

tom

Professor Foltynie is the Exenatide-PD3 Chief Investigator, he is a Professor and Honorary Consultant Neurologist in the Unit of Functional Neurosurgery at UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery since May 2008.

He trained in medicine at UCL, qualifying in 1995 then working in Addenbrooke's Hospital, in Cambridge. From 1999 to 2003, he undertook his PhD in Cambridge looking at the heterogeneity of Parkinson's disease, describing differences in cognitive abilities between patients under the influence of various genes including COMT and BDNF, and Tau. He finished his neurology training between Addenbrooke's Hospital and the National Hospital for Neurology and Neurosurgery in London. While working in London with Dr Limousin, he has developed his interest in Deep Brain Stimulation for Parkinson's disease and has developed collaboration between Parkinson's disease investigators in Cambridge and London.

He is now evaluating factors underlying the heterogeneity of response to Deep Brain Stimulation (DBS), in addition to developing other innovative treatments for Parkinson's disease. These include leading a randomised trial of the GLP-1 receptor agonist Exenatide as a treatment for PD, and UCL's lead for the forthcoming EU sponsored cell transplantation trials for PD. Dr Foltynie is also responsible for patients having DBS for non-PD pathologies at Queen Square including Tourette syndrome and Cluster headache.

His research interests are Parkinson's disease, Deep Brain Stimulation (DBS) and the development of novel treatments for PD; in particular genetic factors that influence treatment response.

Kate Maclagan
Project Manager

Kate graduated from UCL with a PhD in biochemistry in 2009 and went on to spend three years at Barts Health NHS Trust as a Trainee Clinical Scientist.  Following this, she moved into clinical research, taking on the role of Research Coordinator of GIFTS, an EU FP7-funded programme investigating the role of foetal programming in diabetes in South Asians.

Remaining within the field of women's health research, Kate joined the Comprehensive Clinical Trials Unit at UCL in 2013 as the Trial Manager for ASPRE, an international, randomised controlled trial, investigating the use of aspirin in preeclampsia prevention.

In April 2015, Kate was promoted to Clinical Project Manager. Her role entails early-stage trial development, project management of a range of clinical trials over a variety of therapeutic areas and she is also taking the lead on investigational medicinal product within the unit

Grace Auld
Exenatide-PD3 Trial Manager

Grace graduated from UCL with an MSc in Experimental Medicine in 2013. After completion of a laboratory project looking at cirrhotic liver disease in 2014, she went on to work as a Research Assistant in Rheumatology at Guys Hospital. Following this Grace spent a year running hyper-acute interventional research in Stroke at The Royal London Hospital.  

Grace returned to UCL in 2016 to set up and manage a National programme of research in Cardiovascular Disease. In June 2019 she joined the UCL Comprehensive Clinical Trials Unit as the Trial Manager for Exenatide-PD3. 

Jimmy O’Malley
Exenatide-PD3 Data Manager

Jimmy graduated from the University of Kent with a 1st Class Honours BSc degree in Biomedical Science. Following this he went on to work at UCLH as a Clinical Trial Assistant within the haematology department. In April 2019, Jimmy joined the Comprehensive Clinical Trials Unit at UCL as the Data Manager for Exenatide-PD3.

TBC
Exenatide-PD Research Nurse

National Hospital for Neurology & Neurosurgery (NHNN)

EXENATIDE-PD3 is a multi-centre clinical trial being led from the National Hospital for Neurology and Neurosurgery (NHNN)

The NHNN, Queen Square, is the UK's largest dedicated neurological and neurosurgical hospital. It provides comprehensive services for the diagnosis, treatment and care of all conditions that affect the brain, spinal cord, peripheral nervous system and muscles. Services include specialist neurosurgery, a brain tumour unit, the Hyper-acute Stroke Unit (HASU), an acute brain injury unit, the National Prion Clinic, a pioneering neuro-rehabilitation unit, the UK's first interventional MRI scanner, the largest specialised neurosurgical ITU and the only neuromedical ITU in the country. Together with its neighbour, the UCL Institute of Neurology, it is a major international centre for research and training.

Address
National Hospital for Neurology & Neurosurgery
Queen Square 
London 
WC1N 3BG

Telephone
0845 155 50003

Trial protocol

TBC

Additional Information
News
  • 040202019 - EXENATIDE-PD3 Trial has been submitted to the Research Ethics Committee- approval pending
  • EXENATIDE-PD3 Trial has been awarded full Clinical Trials Authorisation by the MHRA. 
Funder – The National Institute for Health Research Efficacy and Mechanism Evaluation (NIHR-EME) Programme

The National Institute for Health Research Efficacy (NIHR) and Mechanism Evaluation (EME) programme funds ambitious studies evaluating interventions with potential to make a step-change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care. Within these studies, EME supports research in the mechanisms of diseases and treatments. EME is a partnership between the Medical Research Council and the National Institute for Health.

Following encouraging results recently published in the Journal of Clinical Investigation describing the progress of a cohort of patients treated with Exenatide for their Parkinson’s disease (PD), NIHR EME has awarded a grant of £2.3 million to Professor Tom Foltynie to pursue this avenue of research.

UCL CCTU

The Comprehensive Clinical Trials Unit (CCTU) at UCL will design, conduct, analyse and report high quality clinical trials and other well designed studies that fit with the research strategies of UCL and UCL Partners.

In pursuit of this Mission, the UCL Comprehensive Clinical Trials Unit will:

  • Develop partnerships with clinical investigators at all relevant institutions
  • Promote a trial governance structure that supports a compliant, risk-based, proportional approach to the application of regulations
  • Provide clinical trials leadership and expertise across the whole range of activities required to deliver trials from concept to dissemination and implementation of research findings
  • Employ highly experienced staff with diverse research interests and expertise in clinical trial methodology to enhance the effectiveness of the research pathway

The UCL CCTU will accomplish its mission through CCTU staff and collaborators supporting adoption of its policies and procedures.

You can find more information about the CCTU in our website.