Exenatide once-weekly as a treatment for Multiple System Atrophy.
Research type
Research Study
Full title
A Phase IIa, open label, single-site, 48 week randomised controlled trial evaluating the safety and efficacy of Exenatide once-weekly in the treatment of patients with Multiple System Atrophy
IRAS ID
279146
Contact name
Thomas Foltynie
Contact email
Sponsor organisation
University College London (UCL)
Eudract number
2020-000122-26
Clinicaltrials.gov Identifier
Z6364106/2019/12/20, Data protection number
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary -
Fifty patients with early stage Multiple System Atrophy (MSA) will be recruited and randomised to receive Exenatide injections, or to act as controls in this open label trial. For half of the patients, Exenatide will be given as a once weekly subcutaneous injection in addition to participant’s regular medication. All patients will continue to receive standard of care treatment for MSA. Detailed assessments will be made of all patients at baseline and periodically for a total of 48 weeks. The primary endpoint will be the difference in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (Parts I and II) at 48 weeks comparing Exenatide treated to best medically treated patients (controls). Secondary measures will include adverse event reports, self-completed questionnaires, and blood test results. Aside from these assessments, all patients will continue any regular MSA medications throughout the trial with adjustments made only according to clinical need.
Standard of care treatment for patients on non IMP arm will be dependant on the patients individual symptoms - there is no broad standard treatment for every patient.Lay Summary of Results -
This phase 2a trial evaluated whether a treatment called exenatide could slow down the rate of progression in a rare and severely disabling neurodegenerative disease called multiple system atrophy (MSA). Exenatide is currently licenced as a type 2 diabetes drug and has previously shown promise in both lab studies and early-stage trials for Parkinson’s disease.
We recruited participants to a single site in London, and the trial was open label meaning that both the participants and researchers knew which treatment was being given. Participants were therefore randomly assigned to receive either exenatide once a week (delivered using an injection pen) or best medical treatment for a period of 48-weeks. All eligible participants were assessed at 12-weekly intervals and were invited back to a single follow-up visit 48-weeks after finishing the main study (called a wash-out period).
The primary way in which we measured whether exenatide was effective was by looking at the participant’s disease severity at the start and end of the trial. We used an assessment called the Unified MSA Rating Scale (UMSARS) which involved a doctor examining the participant’s ability to move and speak, as well as asking the participant about their symptoms over the past 2-weeks. We also looked at thinking and memory, mood and quality of life.
Some participants consented to having a brain scan at the start and end of the trial, and everyone was asked to wear a small sensor on their back for a week to digitally measure their mobility at these time-points too. Blood samples were taken periodically for both safety and research purposes. A sub-group of participants also had a lumbar puncture so that cerebrospinal fluid (the fluid that baths the brain and spinal cord) could be analysed, as we wanted to measure whether exenatide was able to penetrate the brain and exert its effects on various proteins of interest.
Between 23 September 2020 and 06 May 2022, 50 people were recruited and randomly assigned to receive either exenatide or best medical treatment (control group). Two participants in the exenatide group withdrew as they were unable to tolerate the medication and two participants in the control group sourced exenatide privately but were still followed-up.
The frequency of adverse events (i.e. unwanted or undesirable effects that may be related to the study drug) was similar between groups, and included problems like feeling sick or bloated, weight loss, infections of the chest/bladder or feeling tired. There were 41 serious adverse events recorded, 23 in the exenatide group and 18 in the control group. Two people from each group had died during the 48-week exposure period, and 3 people from each group had died during the wash-out period. None of the serious adverse events or deaths were judged to be related to the study drug.
At the end of the trial, we found that the exenatide group had progressed less than the control group as measured by the UMSARS. While this was a positive outcome, we did not observe any other benefits of taking exenatide in how participants felt their symptoms were changing their mood or quality of life. The brain scans, digital mobility measures, and CSF analysis did not differ between the exenatide and control groups either. This discrepancy could be explained by placebo effects and/or observer bias, given the open label nature of our trial. This means that it is possible that the expectations and beliefs of both the participants and researchers collecting the data could have influenced the primary findings. However, the potential positive effects of exenatide on improving symptoms or slowing down disease progression cannot be entirely excluded and warrants further study.
This study was coordinated by the University College London (UCL) Joint Research Office. Data was collected at the Leonard Wolfson Experimental Neuroscience Centre (London, UK), a dedicated clinical trial research facility and part of the UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery.
Funding was received by the John Black Charitable Foundation, Van Andel Institute and Defeat MSA. Support for participant travel was provided by the MSA Trust. Funding for bio-sample analysis was provided by Cure Parkinson’s.
REC name
London - Hampstead Research Ethics Committee
REC reference
20/LO/0473
Date of REC Opinion
11 May 2020
REC opinion
Further Information Favourable Opinion