DEEP BRAIN STIMULATION FOR SEVERE DYSTONIA ASSOCIATED WITH WILSON'S DISEASE. A Prospective Multicenter Meta-analysis of Nof1 Trials
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 3
- 主要终点
- Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores
研究概览
简要总结
Dystonia in Wilson's disease represent a major issue. The persistence of disabling motor symptoms despite medical treatments justifies conducting a study on deep brain stimulation (DBS) in Wilson's disease (WD). For bradykinetic patients, subthalamic nucleus (STN) could be considered as a better target than the globus pallidus (GPi). For patients with hyperkinetic dystonia, the internal globus pallidus (GPi) will be chosen as the target of DBS.
The investigators hypothesize that STN DBS will improve Wilson's disease patients, who, despite copper chelators drugs, are still impaired by severe dystonia and akinesia (more or less associated with other movement disorders).
The investigators primary objective is to demonstrate the efficacy of STN/GPi DBS on dystonia associated with Wilson's disease.
Secondary objectives:
- To evaluate the impact of STN/GPi DBS on other movements disorders (tremor, Parkinsonism, chorea) observed in Wilson's disease.
- To describe cognitive status of patients and to evaluate the consequences of STN/GPi DBS on cognition and behavioral aspects of the disease.
- To evaluate the consequences of the stimulation on speech and swallowing.
- To evaluate the social impact of STN/GPi DBS in Wilson's disease.
- To evaluate the safety of STN/GPi DBS in the specific context of Wilson's disease.
详细描述
4 periods of stimulation on and off, sequence randomized at Day 0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 and < 60 years.
- •Severe neurological form of Wilson's disease with predominant dystonia and akinetic-rigid syndrome, despite optimized treatment stabilized for at least 6 months.
- •Important disability due to abnormal movements (Rankin score=2 to 4).
- •Absence of dementia (MMS > 24 and BREF > 15).
- •Stable psychiatric status and absence of severe depression (BDI <28).
- •Social security coverage.
- •Signature of informed consent. (signature of legal guardian for subjects under protection)
排除标准
- •Severe hepatopathy with coagulation disorders (Platelet count < 100 G / l; INR > 1.5; V factor deficit; low level of fibrinogen < 1g/dL; increased of fibrin degradation products; low level of antithrombin).
- •Liver transplanted patients < 2 years
- •Patients under immunosupressive drugs and corticoids regimen.
- •Participation to another biomedical research involving any drugs.
- •Severe and uncontrolled psychosis or depression.
- •Major atrophy on brain MRI that could represent a problem for leads implantation.
- •Necrosis of the STN/GPi on brain MRI.
- •Female subjects who are pregnant or lactating.
结局指标
主要结局
Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores
时间窗: 21 months
Efficacy will be assessed by the change in the COPM performance and satisfaction scores after each 4 month-period of stimulation on and off, using blinded evaluations. The COPM is a standardized outcome measure widely used in occupational therapy. This tool can facilitate the identification of functional difficulties and individualized subject-specific priorities for intervention, which may not be captured with other standardized scales.
次要结局
- Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score(21 months)
- Change in other movement disorder evaluated by the Clinical global impression (CGI) scale(21 months)
- Cognitive evaluation using the BDI-II (Beck Depression Inventory)(Screening visit (2 days))
- Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV)(Pre-surgery visit (2 days))
- Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))(21 months)
- Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading(21 months)
- Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items)(Pre-surgery visit (2 days))
- Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)(21 months)
- Change in other movement disorder evaluated by the Unified Wilson Disease Rate Scale (UWDRS)(21 months)
- Cognitive evaluation using the Mini Mental Status Examination (MMSE)(Screening visit (2 days))
- Cognitive evaluation using the Trail Making Test (TMT)(Pre-surgery visit (2 days))
- Change in dysarthria and deglutition outcome evaluated by the the "Batterie d'Evaluation de la Dysarthrie" (BECD)(21 months)
- Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI)(21 months)
- Tolerance of Deep Brain Stimulation: occurrence of serious adverse events(23 months)
- Cognitive evaluation using the phonemic verbal fluency task(Pre-surgery visit (2 days))
- Cognitive evaluation using the Frontal Assessment Battery (FAB)(Screening visit (2 days))
- Cognitive evaluation using the Modified Card Sorting Test (MCST)(Pre-surgery visit (2 days))
- Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP)(21 months)
- Change in social outcome evaluated by the Zarit Burden Inventory (ZBI)(21 months)
- Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI)(21 months)
- Change in dysarthria and deglutition outcome evaluated by the maximum phonation time(21 months)
- Change in dysarthria and deglutition outcome evaluated by the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale(21 months)
- Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity(21 months)