European Study of Prodromal iNPH
- Conditions
- Normal Pressure HydrocephalusHydrocephalus
- Interventions
- Procedure: Shunt surgery
- Registration Number
- NCT05910944
- Lead Sponsor
- Johan Virhammar
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group 3 - symptomatic iNPH Shunt surgery Patients with symptomatic iNPH Group 1 - prodromal iNPH Shunt surgery Individuals with typical imaging findings consistent with iNPH but none or too mild symptoms to motivate shunt surgery.
- Primary Outcome Measures
Name Time Method Frequency of patients with prodromal iNPH that requires shunt surgery within 6 years from inclusion. 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 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 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.
- Secondary Outcome Measures
Name Time Method 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 Assess change in parenchymal water content (mL) measured with Synthetic MR and calculate associations between change in parenchymal water and change in symptoms.
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 plasma levels of neurofilament light chain protein (ng/L), Total-tau (ng/L), amyloid beta-42 (ng/L), glial fibrillary acidic protein (ng/L) will be measured using Quanterix (SIMOA).
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 Assess change in cerebral myelin volume (mL) measured with Synthetic MR and calculate associations between change in cerebral myelin volume and change in symptoms.
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 CSF levels of neurofilament light chain protein (ng/L), Total-tau (ng/L), amyloid beta-42 (ng/L), glial fibrillary acidic protein (ng/L) will be measured using Quanterix (SIMOA).
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 Quality of life assessed by EQ-5D-5L (EuroQoL 5 Dimensions 5 Levels). A self-assessment questionnaire with five different aspects of quality of life scored on five-level scales.
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 Assess change in ventricular volume (mL) measured with volumetric magnetic resonance imaging (MRI) and calculate associations between change in ventricular volume and change in symptoms.
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 Semi-quantified levels of approximately 200 proteins are measured with proximity extension assay (Neurology panel and Neuro exploratory panel, Olink.com). Measured semi-quantitative in the unit NPX.
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 Assess change in volume (mL) of white matter hyperintensities (WMH) measured with volumetric magnetic resonance imaging (MRI) and calculate associations between change in WMH and change in symptoms.
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 Assess change in brain morphology assessed with the idiopathic Normal Pressure Hydrocephalus (iNPH) Radscale and calculate associations between change in iNPH Radscale and change in symptoms.
Trial Locations
- Locations (7)
Kuopio University Hospital
🇫🇮Kuopio, Finland
Bellaria Hospital
🇮🇹Bologna, Italy
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Linköping University Hospital
🇸🇪Linköping, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Umeå University Hospital
🇸🇪Umeå, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden