Assessing the Polygenic Burden of Rare Disruptive Mutations in Parkinson's Disease: a Novel Diagnostic Test to Predict Parkinson's Disease Risk
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- identification of variants/mutations
研究概览
简要总结
The project intends to assess the polygenic burden of rare disruptive mutations in Parkinson's disease (PD) and how they influence the phenotype/pathological heterogeneity of disease.
详细描述
The investigators intend to extend the genetic analysis to a cohort of 300 PD cases and 300 healthy subjects (wife / husband of the patients) that will be recruited at Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed.
After signed informed consent patients will be assessed for disease progression (Hoehn and Yahr stadium, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS), Montreal Cognitive Assessment (MoCA) test, no motor symptoms, therapy and levodopa induced Dyskinesia (LID) occurrence). Each patient and control will be subjected to peripheral blood sampling for the isolation of DNA, RNA, plasma and serum. The investigators will use a disease-specific gene panel including about 100 genes related to Parkinson's Disease, autophagy and levodopa induced Dyskinesia (LID).
Bioinformatics analysis will allow to catalog in a database the identified variants/mutations according to their frequency and characteristics.
The investigators will specifically assess if the inheritance of multiple rare deleterious variants in Parkinson's Disease genes is predictive of disease risk.
The presence of one or more variants will be tested for association with phenotypic manifestation of Parkinson's Disease (motor, non-motor, and cognitive signs, as well as age at onset, LID and neuroimaging changes) to assess the variant burden effect on progression, and prognosis of the disease.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Presence of at least two out the following cardinal signs: resting tremor, cogwheel rigidity, bradykinesia, asymmetrical onset of symptoms and symptomatic response to L-dopa (levodopa).
排除标准
- •Previous thalamotomy on the implanted sides;
- •Significant brain atrophy or structural damage seen on CT or MRI;
- •Marked cognitive dysfunction;
- •Active psychiatric symptoms;
- •Concurrent neurological disorders;
- •Other uncontrolled medical disorders.
结局指标
主要结局
identification of variants/mutations
时间窗: two years
assessing if the inheritance of multiple rare deleterious variants in PD genes is predictive of PD risk.
clinical evaluation of PD patients and controls
时间窗: three years
disease progression (Hoehn and Yahr stadium, MDS-UPDRS part III, MoCA test, no motor symptoms, therapy and LID occurrence
association with phenotypic manifestation of PD
时间窗: three years
The presence of one or more variants will be tested for association with phenotypic manifestation of PD (motor, non-motor, and cognitive signs, as well as age at onset, LID and neuroimaging changes) to assess the variant burden effect on progression, and prognosis of the disease.
次要结局
未报告次要终点
研究者
Teresa Esposito
Head of CNR Unit
Neuromed IRCCS