Role of the Striatal Cholinergic System in the Pathophysiology of Dystonia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Binding potential
研究概览
简要总结
Dystonia is defined as a syndrome of sustained muscle contractions resulting in repetitive movements and abnormal postures. DYT1 is the most common form of genetic dystonia, but the link between genomic mutations and phenotypic expression remains largely unknown. Furthermore, secondary forms of dystonia have highlighted the role of the basal ganglia, particularly the putamen in the pathophysiology of the disease. Experimental results in a genetic model of dystonia in rodents suggest that cholinergic inter-neurons (ACh-I) of the putamen play a critical role in the pathological process of plasticity in the cortico-striatal synapse. However, these results have not been demonstrated in humans.
详细描述
The purpose of this study is to demonstrate that the phenotype of dystonia is associated with the degree of striatal ACh-I alterations.
In this molecular imaging study, the investigators will directly test this hypothesis using a PET radiotracer of the vesicular acetylcholine transporter (VAT). Their goal is to explore the relationships between cholinergic dysfunction and clinical disease expression and the associated morphological and functional alterations. The experimental protocol will also include multimodal MRI, MRI diffusion tensor (to study the microscopic structure of white matter) and functional MRI of the resting state (to study the functional organization of cerebral cholinergic networks at rest).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Man or woman 18 to 75 years, with health insurance European health insurance card (for resident patients in EU), insurance by bilateral social security agreement signed between his country and France (for resident patients outside the EU)
- •Diagnosis of dystonia DYT1 confirmed by molecular biology (TORSINE- A gene mutation)
- •Patient who stopped his anticholinergic treatment 48 hours before imaging
排除标准
- •Patients who underwent surgery for deep brain stimulation or under cholinergic treatment.
- •Presence of a counter-indication for MRI
- •Presence of a counter-indication for TEP Scan with [18F]-FEOBV
- •Woman premenopausal without effective ongoing contraception (intrauterine device or combined hormonal)
- •Patient who underwent a PET examination in the previous month
- •Presence of any health problem preventing travel to the imaging service of the University Hospital
- •Being under the legal guardianship of another person or being unable to provide consent to participate
- •Pregnant or breastfeeding woman
研究组 & 干预措施
Cholinergic striatal imaging
Cholinergic striatal imaging (IRM and TEP) to compare the intensity of the binding of cholinergic tracer
干预措施: PET (Positron Emission Tomography) imaging (Radiation)
Cholinergic striatal imaging
Cholinergic striatal imaging (IRM and TEP) to compare the intensity of the binding of cholinergic tracer
干预措施: MRI : Magnetic Resonance Imaging (Other)
结局指标
主要结局
Binding potential
时间窗: Inclusion (V0)
Image (PET) of the intensity of fixation of Cholinergic tracer (Binding potential)
次要结局
未报告次要终点