Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicentric Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Number of steps on the Stand Walk Sit Test
研究概览
简要总结
Therapeutic management of gait disorders in very advanced Parkinson's disease (PD) patients can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related Parkinsonian signs than for gait disorders. Gait disorders could be also partly related to noradrenergic system impairment, pharmacological modulation of both dopamine and noradrenaline pathways could potentially improve the symptomatology. The investigators have demonstrated using an open label study on 17 advanced PD patients that chronic, high doses of methylphenidate (MPD) improved gait, freezing of gait, motor symptoms and attention in the absence of L-Dopa and increased the intensity of response of these symptoms to L-Dopa (Devos et al., 2007). The investigators aimed to confirm their results using a randomized, double-blind, placebo-controlled, parallel-group, multicentric trial. The investigators will assess the clinical value of chronic, high doses (1 mg/kg/day) of MPD vs placebo in 88 non demented PD patients suffering from severe gait disorders with freezing despite their use of optimal dopaminergic doses and eventually STN stimulation parameters. Efficacy will be assessed directly and on video in the absence of L-Dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using Stand Walk Sit test (primary criteria), the "Freezing Of Gait trajectory", RGSE scale, the UPDRS scores, the dyskinesia rating scale, Achiron scales and using auto-questionnaires of Giladi, ABC scale and PDQ 39. Attention will be assessed using reactions times. Drowsiness will be assessed using Epworth and Parkinson's disease Sleep Scales. Apathy and depression will be monitored with Lille Apathy Rating Scale, MADRS, BPRS, MINI and psychiatric interview. Cardiologic and general tolerance will be also monitored. This study could lead to propose methylphenidate with a good efficacy/ risk balance in advanced PD patients suffering from severe gait disorders with freezing of gait, drowsiness and attention deficit.
详细描述
Overall study duration: 2 years. Planned inclusion period: 12 months. Study duration for individual patients: 4 months and 2 weeks(2 weeks between screening and randomization, 3 months of double-blind treatment and then a 4-week wash-out period).
Primary objective (V1 and V4):
To assess efficacy of methylphenidate treatment on severe gait disorders including freezing assessed by the Stand Walk Sit Test in patients with advanced Parkinson's disease without dementia or depression and under subthalamic stimulation
Additional Efficacy Endpoints (V1 and V4):
- Gait and motor symptoms: the "Freezing Of Gait trajectory", RGSE scale, the UPDRS scores (partI, II, III, IV), the dyskinesia rating scale
- auto-questionnaires of Giladi, ABC scale and PDQ 39
- Attention: simple and complex reactions times
- Drowsiness: Epworth and Parkinson's disease Sleep Scales
- Apathy Lille Apathy Rating Scale
- Depression and other psychiatric disorders: MADRS, BPRS, MINI and psychiatric interview
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Parkinson's disease of more than 5 years
- •Subthalamic nucleus stimulation
- •Gait disorders impeding moderately to severely the activities of daily living
- •gait disorders including freezing of gait
- •able to walk without physical assistance
排除标准
- •Dementia (MMSE < 27 et score de Mattis < 130)
- •Requiring dopatherapie modification
- •Requiring subthalamic stimulation parameters adaptation
- •Psychiatric disorders: hallucinations, unstable thymic disorders, psychosis)
- •Cardiac disorders: dysrhythmia or unstable arterial hypertension
- •Unstable or severe medical illness
- •intolerance or contraindication to methylphenidate
研究组 & 干预措施
placebo
tablets of placebo 3 time a day
干预措施: placebo (Drug)
methylphenidate
methylphenidate 10 mg tablets (1 mg /kg /day) 3 time a day
干预措施: methylphenidate (Drug)
结局指标
主要结局
Number of steps on the Stand Walk Sit Test
时间窗: 3 months
次要结局
- time on the stand walk sit test(3 months)
- number of freezing on the FOG trajectory(3 months)
- UPDRS(3 months)
- RGSE(3 months)
- psychiatric interview(3 months)
- Cardiac examination with ECG and blood pressure(3 months)