European Study of Prodromal iNPH
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorJohan Virhammar
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Group 1 - prodromal iNPH
Evans index > 0.3
Disproportionately enlarged subarachnoid space hydrocephalus (DESH) - defined as: enlarged ventricles, dilated sylvian fissures and tight sulci at the high convexity.
Normal gait pattern, or slight disturbance of the gait pattern that is not considered to be caused by a disease in the central nervous system (CNS).
Disqualifiers
Group 1 - prodromal iNPH
Contraindication for MRI
Other serious disease with expected survival less than three years
non-communicating hydrocephalus
Trial population
Patients in Group 1 can be included from patients referred to a tertiary hydrocephalus center after investigations/work-up have shown too mild symptoms to motivate shunt surgery. Healthy age-matched controls (Group 2) can be included by advertising and by asking relatives to patients in Group 1 and Group 3. For each included individual in Group 1 (prodromal iNPH), two patients are included in Group 3 (symptomatic iNPH). These patients are consecutively included at each center from routine patients that are planned for shunt surgery. They should be age matched with the individual in Group 1 (+/- 3 years).
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Shunt surgery
Procedure/SurgeryShunt surgery according to each local centers routine
Treatment groups
140 Participants
are divided into 3 treatment groupsGroup A: Group 1 - prodromal iNPH1 intervention
Group B: Group 2 - Healthy controls0 interventions
Group C: Group 3 - symptomatic iNPH1 intervention
Trial outcomes
Primary outcomes
1
Frequency of patients with prodromal iNPH that requires shunt surgery within 6 years from inclusion.
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.
Time frame
From date of inclusion until decision of shunt surgery, assessed up to 72 months2
Frequency of patients with prodromal iNPH that progress to symptomatic iNPH
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.
Time frame
From date of inclusion until 20 points reduction in total iNPH-scale score or 20% reduction in gait speed, assessed up to 72 months3
Post operative improvement in iNPH-scale score in patients with mild, moderate and severe preoperative symptoms
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.
Time frame
Change from preoperative (last visit before surgery) iNPH scale at 3 months, 12 months, 36 months and 60 months follow-up.Secondary outcomes
1
Change in white matter hyperintensities (WMH)
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.
Time frame
Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months2
Change in brain morphology
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.
Time frame
Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months3
Change in ventricular volume
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.
Time frame
Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months4
Change in parenchymal water content
Assess change in parenchymal water content (mL) measured with Synthetic MR and calculate associations between change in parenchymal water and change in symptoms.
Time frame
Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Johan Virhammar
Lead sponsor
Uppsala University Hospital
Sponsor institution
Swedish Society for Medical Research
Collaborator
Source ClinicalTrials.gov