Simvastatin as a Neuroprotective Treatment for Parkinson's Disease: a Double-blind, Randomised, Placebo Controlled Futility Study in Patients of Moderate Severity.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 235
- 试验地点
- 24
- 主要终点
- Change in MDS-UPDRS part III (OFF) score
研究概览
简要总结
Participants are randomly allocated to one of two treatment groups. In one group, participants are given capsules of simvastatin to take orally (by mouth) for 24 months. In the other group, participants are given placebo (dummy) capsules to take orally for 24 months. At the start of the study, when they receive their medication, participants complete a number of questionnaires and motor (movement) tests (a walking test and a finger tapping test). Participants in both groups also attend a further 6 clinic visits after 1, 6, 12, 18 and 24 and 26 months, where they are asked about their health and any medication they are taking, as well as repeating the questionnaires and motor tests. For 4 of the clinic visits, the participants will be asked to attend in the 'OFF medication' state (having omitted their usual PD medication) so that the researchers can get a true picture of their disease without it being masked by their normal medication.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of idiopathic PD
- •Modified Hoehn and Yahr stage ≤ 3.0 in the ON medication state
- •Age 40-90 years
- •On dopaminergic treatment with wearing-off phenomenon
- •Able to comply with study protocol and willing to attend necessary study visits
排除标准
- •Diagnosis or suspicion of other cause for parkinsonism
- •Known abnormality on CT or MRI brain imaging considered to be causing symptoms or signs of neurological dysfunction, or considered likely to compromise compliance with study protocol
- •Concurrent dementia defined by MoCA score <21
- •Concurrent severe depression defined by MADRS score >31
- •Prior intracerebral surgical intervention for PD including deep brain stimulation, lesional surgery, growth factor administration, gene therapy or cell transplantation
- •Already actively participating in a research study that might conflict with this trial
- •Prior or current use of statins as a lipid lowering therapy
- •Intolerance to statins
- •Untreated hypothyroidism
- •End stage renal disease (creatinine clearance <30 mL/min) or history of severe cardiac disease (angina, myocardial infarction or cardiac surgery in preceding two years)
- •eGFR <30 mL/min
- •History of alcoholism or liver impairment
- •Creatine kinase (CK) >1.1 x upper limit of normal (ULN)
- •Aspartate transaminase (AST) or alanine transaminase (ALT) >1.1 x ULN
- •Females who are pregnant or breast feeding or of child-bearing potential and unwilling to use appropriate contraception methods whilst on trial treatment
- •Currently taking any medication contraindicated with simvastatin use (Appendix 2)
- •Any requirement for statin use
- •Regular participation in endurance or high-impact sports
- •Unable to abstain from consumption of grapefruit-based products
研究组 & 干预措施
Simvastatin
A one month low dose phase of 40mg oral simvastatin daily will be followed by a 23 month high dose phase of 80mg oral simvastatin daily and a final two month phase off trial medication
干预措施: Simvastatin (Drug)
Matched Placebo
A one month low dose phase of 40mg matched placebo daily will be followed by a 23 month high dose phase of 80mg matched placebo daily and a final two month phase off trial medication
干预措施: Matched Placebo (for Simvastatin) (Drug)
结局指标
主要结局
Change in MDS-UPDRS part III (OFF) score
时间窗: Baseline and 24 Months
The MDS-UPDRS is the standard validated tool for the assessment of patients with Parkinson's Disease. This scale includes subsections collecting data regarding the impact of PD on a patient's mood and mental state, (UPDRS part I), their activities of daily living (UPDRS part II) an examination of the motor features of PD (UPDRS part III), and complications arising from the use of dopamine replacement (part IV).
次要结局
- Parkinson's disease Questionnaire (PDQ-39)(at 12 and 24 months)
- MDS-UPDRS part II subscale score in the practically defined ON state(at 12 and 24 months)
- Non-Motor Symptom assessment scale (NMSS)(at 12 and 24 months)
- King's PD pain scale (KPPS)(at 12 and 24 months)
- MDS-UPDRS total score in the practically defined ON state(at 12 and 24 months)
- Timed motor tests - finger tapping and timed walk test (10MWT) in the OFF state, electromagnetic sensor (EMS) assessment in the OFF and ON state(at 12 and 24 months)
- Montgomery and Asberg Depression Rating Scale (MADRS)(at 12 and 24 months)
- EuroQoL 5D-5L health status questionnaire (EQ-5D-5L)(at 12 and 24 months)
- Incidence of diabetes mellitus, using a glycated haemoglobin (HbA1c) level of 6.5% (48mmol/mol) as diagnostic of diabetes mellitus.(at 24 months)
- Cholesterol levels (total, HDL, total/HDL ratio)(at 12 and 24 months)
- Safety and tolerability of trial medication by adverse events (AEs) review.(at 12 and 24 months)
- The Addenbrooke's Cognitive Assessment-III (ACE-III)(at 12 and 24 months)
- Changes in PD medication as measured by levodopa-equivalent dose (LED)(at 12 and 24 months)