Multiple System AtrophyPhase 2MSANCT04431713
Exenatide Once-weekly as a Treatment for Multiple System Atrophy
A Phase 2 study testing Exenatide Pen Injector [Bydureon] in people with Multiple System Atrophy, run by University College, London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Multiple System Atrophy
- What is being tested?
- Exenatide Pen Injector [Bydureon]
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Sep 2020to 22 Mar 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants aged 30-80 years old with a diagnosis of Possible or Probable MSA of the parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (Gilman et al. 2008).
- Participants who are less than five years from the time of documented MSA diagnosis or from the time of documented parkinsonian / ataxic neurological condition that later turns out to be MSA.
- Participants who are able to walk at least 10 metres with or without assistance. Participants with an anticipated survival of at least three years in the opinion of the investigator.
- Participants that are willing to adhere to the study drug regimen.
- Participants that are willing and able to perform all protocol-specified assessments and comply with the study visit schedule.
- Females of childbearing potential and male participants with partners of childbearing potential must agree to use an effective method of contraception from the time consent is signed until 10 weeks after treatment discontinuation. Females of childbearing potential have a negative pregnancy test within 7 days prior to being randomised.
- Willing and able to provide written informed consent.
- Subjects who are not able to write may give verbal consent in the presence of at least one witness, and the witness should sign the informed consent form.
Who cannot join
- Females who are pregnant, planning pregnancy or breastfeeding.
- Women of child-bearing potential who do not practice an acceptable method of birth control. Subjects who meet any of the following criteria which tend to suggest advance disease:
- Speech impairment as assessed by a score of ≥ 3 on UMSARS question 1
- Swallowing impairment as assessed by a score of ≥ 3 on UMSARS question 2
- Impairment in ambulation as assessed by a score of ≥ 3 on UMSARS question 7
- Falling more frequently than once per week as assessed by a score of ≥ 3 on UMSARS question 8. Participants with a clinically significant or unstable medical or surgical condition, which in the opinion of the investigator might preclude safe completion of the study.
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- Participants with active malignant neoplasms or history of malignant neoplasm in the last 5 years. Participants with movement disorders other than MSA.
- Concurrent dementia defined by a score lower than 21 on the MoCA.
- Concurrent severe depression defined by a score of ≥30 on the Beck Depression Inventory-II.
- History of deep brain stimulation surgery.
- Participants who have taken any investigational products within 90 days prior to baseline.
- Participants with a BMI < 18.5.
- Participants with diabetes, end stage renal disease or severely impaired renal function.
- History of clinically significant cardiac disease, pancreatitis and/or alcoholism.
- Participants with severe gastrointestinal disease including gastroparesis.
- Ongoing treatment with sulphonylurea.
- Known allergies to the IMP and excipients of IMP.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leonard Wolfson Experimental Neurology Centre, National Hospital of Neurology and Neurosurgery, UCLH NHS Foundation trust
London, WC1N 3BG
About this study
Official title: An 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
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.
Read the detailed description
Fifty patients with early stage MSA will be recruited and randomised to receive Exenatide injections, or to act as controls in this open label trial.
Once a potential participant has been identified they will receive a patient information leaflet, and will be given a minimum of 24 hours to read this before being recruited on to the trial. Patients will need to be eligible for the trial by meeting the inclusion criteria.
During pre-treatment there will be a screening visit and a baseline visit. Pre-treatment assessments will include: demographics, medical history, family history, any previous genetic tests recorded, previous drug compliance issues recorded, physical examination, neurological examination, 12-lead ECG, routine bloods (FBC, U\&E, LFT, glucose, amylase, HbA1c, PT and APTT), height, weight, vital signs, serum or urine pregnancy tests (for women of childbearing potential), MoCA, BDI-II and Concomitant medications. Patients will then wear a sensor attached to their lower back for a week. They will then return for their baseline visit. At the baseline visit assessments will include: physical exam, neurological exam, lumbar puncture for CSF collection, serum collection, fasting blood tests, vital signs, UMSARS, COMPASS Select, COMPASS Change scale, timed motor tests, The Unified Dystonia Rating Scale, MoCA, BDI-II, Concomitant medication review and adverse event review. Participants will then be randomised to both control arm or trial drug arm and receive the according treatment. The baseline visit will also include a training session for self-administration of IMP.
Patients randomised to receive the trial drug will receive 2mg Exenatide once a week for 48 weeks via subcutaneous injection. Follow up visits will be every 12 weeks and patients will be given a sufficient supply to last them till their next follow up appointment (can be stored in fridge at home). They will also be given a dosing diary to record the time and day of injection administration.
Patients will continue to attend their normal neurology appointments as well as trial specific appointments. Patients will have a telephone call with the research nurse at week 4. Thereafter detailed assessments including Physical and Neurological exam, ECG's, Movement tests Including the Unified Multiple System Atrophy Rating Scale (videotaped), concomitant medications review, adverse event review, and blood sampling at baseline and every 12 weeks for a total of 48 weeks. Each patient will also have a Lumbar Puncture at baseline and at their final visit.
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 to best medically treated patients. 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.
- Conditions
- Multiple System Atrophy
- Being tested
- Exenatide Pen Injector [Bydureon]
- Medical subject headings
- Multiple System Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exenatide Pen Injector [Bydureon]Drug
Exenatide is a treatment licensed for use in Type 2 diabetes.
| Study group | Role | What they receive |
|---|---|---|
| Exenatide | Experimental | Not described Receives: Drug: Exenatide Pen Injector [Bydureon] |
| Standard of care | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in UMSARS Score (Parts I+II) From Baseline
The primary endpoint is the total Unified Multiple System Atrophy Rating Scale (UMSARS) score (Parts I and II), exploring the change from baseline overtime (evaluated at 48-weeks). Part I is a 12-item historical interview (max score 48) and Part II is a 14-item clinical examination (max score 56). Part I and II are added together to give a total score, which can range from 0 to 104. Higher scores indicate worse disease severity.
Measured: Baseline and 48 weeks
Secondary outcomes (8)
Loss of Independent Ambulation
Proportion of participants with loss of independent ambulation, defined by a score of 4 on the UMSARS-I Item 7 (walking) at 48 weeks.
Measured: 48 weeks
Multiple System Atrophy Quality of Life (MSA-QoL) Scale
The Multiple System Atrophy Quality of Life (MSA-QoL) scale measured health-related quality of life across three subscales (motor, nonmotor, and emotional/social functioning). Each item (40 in total) has five increasing levels of impairment (0 to 4), with 0 representing no impairment and 4 representing extreme impairment. Scores for the three subscales were generated by summing items and transformed to a range of 0 to 100 (100 × [(observed score minus min possible score)/(max possible score minus min possible score)]).
Measured: 48 weeks
Number of Falls
Number of falls reported by the participant at 48-weeks.
Measured: 48 weeks
Milestones on UMSARS Part 1 (Speech, Swallow and Falling)
The UMSARS Part 1 is 12-item sub-scale which comprises a historic review of disease-related impairments. A single score using a 0 (no impairment) to 4 (severe impairment) was generated for each item (max score 48 points). We examined the proportion of participants reaching a score of ≥ 3 on UMSARS item 1 (speech), item 2 (swallowing) and item 8 (falling) by 48 weeks.
Measured: 48 weeks
Clinical Global Impression (CGI) Scale
The CGI evaluates the change from the initiation of treatment on a seven-point scale (1 = =very much improved to 7 = very much worse since the initiation of treatment). A single score at 48 weeks was recorded.
Measured: 48 weeks
Montreal Cognitive Assessment (MoCA)
The MoCA is a brief cognitive scale (scored out of 0-30 points). A score of 26 or more reflects normal cognitive abilities, whereas lower scores indicate cognitive impairment. The difference between groups (total score out of 30) was explored at 48 weeks.
Measured: 48 weeks
UMSARS Part IV
The UMSARS Part 4 measures global disability (1 item) scored from 1 (completely independent) to 5 (totally dependent and helpless. Bedridden).
Measured: Score at 48 Weeks
Beck Depression Inventory II (BDI-II)
The BDI-II is a self-report questionnaire designed to measure the severity of depression symptomatology (scored out of 0-63 points). A score of 13 or less indicated minimal, 14-19 indicated mild, 20-28 indicated moderate and 29-63 indicated severe depression. The difference between groups was explored at 48 weeks.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start16 Sep 2020
- Primary completion22 Mar 2024
- Study completion22 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04431713
- Sponsor's protocol ID
- 125591
- Other IDs
- 2020-000122-26
- Acronym
- MSA
- Status last verified
- Jun 2025
- First submitted
- 29 May 2020
- Last updated
- 27 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymised data will be made available from those patients who have provided consent to do so, following completion of trial data analysis, for any reasonable requests.
Publications
Athauda D, Foltynie T. Insulin resistance and Parkinson's disease: A new target for disease modification? Prog Neurobiol. 2016 Oct-Nov;145-146:98-120. doi: 10.1016/j.pneurobio.2016.10.001. Epub 2016 Oct 3.
PubMed 27713036Athauda D, Foltynie T. The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action. Drug Discov Today. 2016 May;21(5):802-18. doi: 10.1016/j.drudis.2016.01.013. Epub 2016 Feb 3.
PubMed 26851597Athauda D, Gulyani S, Karnati HK, Li Y, Tweedie D, Mustapic M, Chawla S, Chowdhury K, Skene SS, Greig NH, Kapogiannis D, Foltynie T. Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial. JAMA Neurol. 2019 Apr 1;76(4):420-429. doi: 10.1001/jamaneurol.2018.4304.
PubMed 30640362Athauda D, Maclagan K, Budnik N, Zampedri L, Hibbert S, Skene SS, Chowdhury K, Aviles-Olmos I, Limousin P, Foltynie T. What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson's Disease: A Post Hoc Analysis. J Parkinsons Dis. 2018;8(2):247-258. doi: 10.3233/JPD-181329.
PubMed 29843254Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J, Li Y, Aviles-Olmos I, Warner TT, Limousin P, Lees AJ, Greig NH, Tebbs S, Foltynie T. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Oct 7;390(10103):1664-1675. doi: 10.1016/S0140-6736(17)31585-4. Epub 2017 Aug 3.
PubMed 28781108Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T. Exenatide and the treatment of patients with Parkinson's disease. J Clin Invest. 2013 Jun;123(6):2730-6. doi: 10.1172/JCI68295.
PubMed 23728174Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Kahan J, Ell P, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson's disease. J Parkinsons Dis. 2014;4(3):337-44. doi: 10.3233/JPD-140364.
PubMed 24662192Bassil, Fares, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Pierre-Olivier Fernagut, and Wassilios G. Meissner. 2017. "Brain Insulin Resistance in Parkinson's Disease [MDS Abstracts]." Movement Disorders 32 (suppl.
Bassil F, Canron MH, Vital A, Bezard E, Li Y, Greig NH, Gulyani S, Kapogiannis D, Fernagut PO, Meissner WG. Insulin resistance and exendin-4 treatment for multiple system atrophy. Brain. 2017 May 1;140(5):1420-1436. doi: 10.1093/brain/awx044.
PubMed 28334990Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE; DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010 Aug 7;376(9739):431-9. doi: 10.1016/S0140-6736(10)60590-9. Epub 2010 Jun 26.
PubMed 20580422Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.
PubMed 21307137Consoli A, Formoso G. Potential side effects to GLP-1 agonists: understanding their safety and tolerability. Expert Opin Drug Saf. 2015 Feb;14(2):207-18. doi: 10.1517/14740338.2015.987122. Epub 2014 Dec 12.
PubMed 25496749Cork SC, Richards JE, Holt MK, Gribble FM, Reimann F, Trapp S. Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain. Mol Metab. 2015 Aug 5;4(10):718-31. doi: 10.1016/j.molmet.2015.07.008. eCollection 2015 Oct.
PubMed 26500843D'Amelio M, Ragonese P, Callari G, Di Benedetto N, Palmeri B, Terruso V, Salemi G, Famoso G, Aridon P, Savettieri G. Diabetes preceding Parkinson's disease onset. A case-control study. Parkinsonism Relat Disord. 2009 Nov;15(9):660-4. doi: 10.1016/j.parkreldis.2009.02.013. Epub 2009 Apr 7.
PubMed 19356970Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, Schimke N, Trenkwalder C, Sixel-Doring F, Herting B, Kamm C, Gasser T, Sawires M, Geser F, Kollensperger M, Seppi K, Kloss M, Krause M, Daniels C, Deuschl G, Bottger S, Naumann M, Lipp A, Gruber D, Kupsch A, Du Y, Turkheimer F, Brooks DJ, Klockgether T, Poewe W, Wenning G, Schade-Brittinger C, Oertel WH, Eggert K. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010 Jan 15;25(1):97-107. doi: 10.1002/mds.22732.
PubMed 20014118