European Study of Prodromal iNPH
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 7
- 主要终点
- Frequency of patients with prodromal iNPH that requires shunt surgery within 6 years from inclusion.
研究概览
简要总结
To investigate if progression from prodromal into symptomatic NPH can be predicted from advanced neuroimaging, biomarkers in cerebrospinal fluid (CSF) and plasma and investigate the unknown mechanisms causing deterioration by investigating longitudinal changes in the above-mentioned variables. Three different cohorts with both asymptomatic and symptomatic patients as well as healthy controls will be investigated over time, both without intervention and before and after shunt surgery.
详细描述
Three prospective cohorts will be included during five years from seven European centers.
Group 1 - Prodromal NPH. Patients with imaging features associated with iNPH and no symptoms, or to little symptoms to motivate shunt surgery, will be included prospectively. At baseline, an MRI of the brain will be performed and a lumbar puncture to collect CSF as well as blood samples. The patients will be followed with a standardized scheme that will go on for as long as the patient chose to remain in the study or until the patient develops symptoms and are referred for shunt surgery. The study scheme includes repeated assessments of symptoms, MRI of the brain, CSF samples and blood samples. The following study visits are planned before surgery: baseline, 6 months, 1st year, 2nd year, 4th year, 6th year. After shunt surgery, clinical evaluations and blood samples will be collected at four assessments during five years post-operative.
Group 2 - Healthy controls - For every patient in Group 1, one patient can be included in Group 2. They will be investigated with the same protocol as Group 1 but only follow the protocol for one cycle (Baseline to year 4).
Group 3 - Symptomatic NPH - For each included individual in Group 1 (prodromal NPH), two patients are included in Group 3 (symptomatic NPH). These patients are consecutively included at each centre from routine patients that are planned for shunt surgery. They should be age matched with the individual in Group 1 (+/- 3 years). Their investigations will be identical with the post-operative routine for five years as Group 1.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Frequency of patients with prodromal iNPH that requires shunt surgery within 6 years from inclusion.
时间窗: From date of inclusion until decision of shunt surgery, assessed up to 72 months
Symptoms are assessed with the idiopathic Normal Pressure Hydrocephalus scale (iNPH-scale) with addition of the gait tests: 10 meter walking in maximum speed, timed up and go test (TUG) and 3 m walking backwards. Each center decides when symptoms have progressed enough to motivate shunt surgery according to local traditions and routine. Low values in time and steps of the gait tests indicate good performance and high values of the iNPH-scale (range: 0-100) indicates good performance.
Post operative improvement in iNPH-scale score in patients with mild, moderate and severe preoperative symptoms
时间窗: Change from preoperative (last visit before surgery) iNPH scale at 3 months, 12 months, 36 months and 60 months follow-up.
Differences in short (3 and 12 months) and long-term outcome (36 and 60 months) measured as change between preoperative and postoperative iNPH-scale score will be compared between patients with mild, moderate and severe preoperative symptoms. High values of the iNPH-scale (range: 0-100) indicates good performance.
Frequency of patients with prodromal iNPH that progress to symptomatic iNPH
时间窗: From date of inclusion until 20 points reduction in total iNPH-scale score or 20% reduction in gait speed, assessed up to 72 months
Symptoms are assessed with the iNPH-scale with addition of the gait tests: 10 meter walking in maximum speed, timed up and go test (TUG) and 3 m walking backwards. A patient is considered symptomatic when total iNPH-scale is reduced by at least 20 points or the mean speed of the gait tests are reduced by 20%. Low values in time and steps of the gait tests indicate good performance and high values of the iNPH-scale (range: 0-100) indicates good performance.
次要结局
- Change in parenchymal water content(Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Changes in plasma biomarkers(Change from baseline at 6 months, 12 months, 24 months, 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Change in cerebral myelin volume(Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Changes in cerebrospinal fluid (CSF) biomarkers(Change from baseline at 6 months, 12 months, 24 months, 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Change in quality of life(Change from baseline at 6 months, 12 months, 24 months, 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Change in ventricular volume(Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Changes in plasma and cerebrospinal fluid (CSF) proteins(Change from baseline at 6 months, 12 months, 24 months, 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Change in white matter hyperintensities (WMH)(Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months)
- Change in brain morphology(Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months)
研究者
Johan Virhammar
Associate professor
Uppsala University Hospital