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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in UMSARS Score (Parts I+II) From Baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
- •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.
研究组 & 干预措施
Exenatide
干预措施: Exenatide Pen Injector [Bydureon] (Drug)
结局指标
主要结局
Change in UMSARS Score (Parts I+II) From Baseline
时间窗: Baseline and 48 weeks
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.
次要结局
- Loss of Independent Ambulation(48 weeks)
- Multiple System Atrophy Quality of Life (MSA-QoL) Scale(48 weeks)
- Number of Falls(48 weeks)
- Milestones on UMSARS Part 1 (Speech, Swallow and Falling)(48 weeks)
- Clinical Global Impression (CGI) Scale(48 weeks)
- Montreal Cognitive Assessment (MoCA)(48 weeks)
- UMSARS Part IV(Score at 48 Weeks)
- Beck Depression Inventory II (BDI-II)(48 weeks)