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Exenatide Once-weekly as a Treatment for Multiple System Atrophy (MSA)

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ClinicalTrials.gov Identifier: NCT04431713
Recruitment Status : Recruiting
First Posted : June 16, 2020
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief 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.


Condition or disease Intervention/treatment Phase
Multiple System Atrophy Drug: Exenatide Pen Injector [Bydureon] Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : April 26, 2022
Estimated Study Completion Date : April 26, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
Experimental: Exenatide Drug: Exenatide Pen Injector [Bydureon]
Exenatide is a treatment licensed for use in Type 2 diabetes.

No Intervention: Standard of care



Primary Outcome Measures :
  1. To collect data to estimate the effectiveness of Exenatide in modifying disease progression of patients with Multiple System Atrophy [ Time Frame: 48 weeks ]
    The primary endpoint will be the difference in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (Parts I and II)


Secondary Outcome Measures :
  1. The proportion of patients with loss of independent ambulation by the end of the study [ Time Frame: 48 weeks ]
    Defined by the score of 3 or more in UMSARS-I item 7 - walking

  2. The difference in the Multiple System Atrophy Quality of Life (MSA QoL) scale [ Time Frame: 48 weeks ]
    Defined by completion of QoL scale

  3. The difference at week 48 in UMSARS III and IV (The proportion of patients with loss of independent ambulation by the end of the study) [ Time Frame: 48 weeks ]
    Defined by UMSARS III and IV

  4. The difference in anti-parkinsonian or anti-orthostatic hypotension drugs [ Time Frame: 48 weeks ]
  5. The number of falls [ Time Frame: 48 weeks ]
  6. The proportion of patients reaching a score of 3 or more on UMSARS-I items 1 (speech), 2 (swallowing) and 8 (falling) [ Time Frame: 48 weeks ]
  7. The difference at week 48 in clinical global impression (CGI); difference at week 48 in Montreal Cognitive Assessment (MoCA) scores [ Time Frame: 48 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

    1. Speech impairment as assessed by a score of ≥ 3 on UMSARS question 1
    2. Swallowing impairment as assessed by a score of ≥ 3 on UMSARS question 2
    3. Impairment in ambulation as assessed by a score of ≥ 3 on UMSARS question 7
    4. 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04431713


Contacts
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Contact: Tom Foltynie 020 3448 4531 t.foltynie@ucl.ac.uk
Contact: Dilan Athauda d.athauda@nhs.net

Locations
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United Kingdom
Leonard Wolfson Experimental Neurology Centre, National Hospital of Neurology and Neurosurgery, UCLH NHS Foundation trust Recruiting
London, United Kingdom, WC1N 3BG
Contact: Tom Foltynie       tom.foltynie@nhs.net   
Contact: Shazia Begum       shazia.begum4@nhs.net   
Sponsors and Collaborators
University College, London
Publications:
Bassil, 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.

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT04431713    
Other Study ID Numbers: 125591
2020-000122-26 ( EudraCT Number )
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: November 5, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Multiple System Atrophy
Shy-Drager Syndrome
Atrophy
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists