A Randomized, Double-blind, Placebo-controlled Trial of Urate-elevating Inosine Treatment to Slow Clinical Decline in Early Parkinson's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 298
- 试验地点
- 62
- 主要终点
- Rate of Clinical Decline
研究概览
简要总结
A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial to determine whether oral inosine dosed to moderately elevate serum urate (from ≤5.7 mg/dL to 7.1-8.0 mg/dL) over 2 years slows clinical decline in early PD.
Clinical decline will be assessed as change in the primary outcome variable of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a composite scale comprising patient- and clinician-reported outcomes.
详细描述
Capsules containing 500 mg of inosine (active drug) or ~500 mg of lactose (placebo) will be taken orally up to two capsules three times per day (i.e., up to 3 g/day) for 24 months. In the inosine-treated group the number of capsules taken per day will be titrated to serum urate levels - measured at trough at study visits no more than three months apart - in order to achieve concentrations of 7.1-8.0 mg/dL. Initial dosing will be tailored to individualized factors including gender and pretreatment serum urate, and then advanced gradually toward the projected target dose. Adjustments in dosing of placebo capsules in the control arm will be algorithm-based to match dosing of inosine capsules in the active drug arm.
Following study drug discontinuation all subjects will be followed during a 3-month wash-out period by telephone calls and a final study visit. All study visits after screening will include measurement of the primary outcome variable (MDS-UPDRS) and most will include secondary outcome variables: adverse events, dose adjustments, disability warranting initiation of dopaminergic therapy, Quality of Life in Neurological Disorders (Neuro-QOL), 39-item Parkinson's Disease Questionnaire (PDQ-39), Schwab & England Activities of Daily Living (S&E ADL) scale, Montreal Cognitive Assessment (MoCA), and orthostatic vital signs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Inosine
Inosine will be dosed by titrating the number of capsules taken daily to achieve an elevation of serum urate to trough levels of 7.1 to 8.0 mg/dL.
干预措施: Inosine (Drug)
Placebo
Placebo will be dosed to match the capsule titrations of the inosine group.
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of Clinical Decline
时间窗: two years
The primary outcome of the trial is rate of change in the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) I-III total score over 24 months estimated from a shared-baseline, random-slopes mixed model, censoring follow-up of subjects after initiation of dopaminergic therapy. Parts I-III of the MDS-UPDRS include ratings of non-motor experiences of daily living, motor experiences of daily living, and a motor examination. The MDS-UPDRS is assessed on a 5-point Likert scale ranging from 0 to 4 where higher scores imply worse symptoms. Parts I-III contain 59 total questions (13 in Part I, 13 in Part II, and 33 in Part III). Total scores for Parts I-III are calculated as simple sums of component items with mean imputation by Part if no more than 1, 2, or 7 items are missing for Parts I through III, respectively. Total scores may range from 0 to 236, with 0 meaning no symptoms and 236 meaning worse symptoms.
次要结局
- Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL)(two years)
- Rate of Developing Adverse Effects(two years)
- Percentage of Participants Developing Disability Warranting Dopaminergic Therapy Over Time(two years)
- Symptomatic Effects(three months (after both initiation and discontinuation of study drug))
- Percentage Developing Adverse Effects(two years)
- Clinical Efficacy: Rate of Change in Parkinson's Disease Questionnaire - 39 Item Version (PDQ-39) Scale(two years)
- Clinical Efficacy: Rate of Change in Quality of Life in Neurological Disorders (Neuro-QOL) Depression Module(two years)
- Clinical Efficacy: Rate of Change in Montreal Cognitive Assessment (MoCA)(two years)
- Percentage of Subjects Tolerant of the Treatment(three months; two years)
- Clinical Efficacy: Rate of Change in Schwab and England Scale(two years)
研究者
Michael Alan Schwarzschild
Chair, SURE-PD3 Steering Committee
Massachusetts General Hospital