MRI-Volumetry in the Evaluation of Shunt Treatment for Hydrocephalus

Study Overview
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Brief Summary
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This randomized, double-blinded, cross-over study aim to evaluate the effects of shunt treatment in idiopathic normal pressure hydrocephalus (iNPH) by measuring cerebral ventricular volume and clinical symptoms at different shunt opening pressures. Further, proteins in the cerebrospinal fluid (CSF) will be compared before and after shunt surgery.

Detailed Description
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The participants are evaluated before surgery and one month, two months, three months and three months plus one day after surgery. At each evaluation point a MRI of the brain with volumetric sequences is performed and clinical data is collected (Walking speed and steps for Time up and go, 10m walking and 3m walking backwards. Mini Mental State Examination, balance, gait, self rating of incontinence, Epworth Sleepiness Scale). At surgery, all patients are given a ventriculoperitoneal (VP) shunt (Strata ® ) with an opening pressure setting of 1.5. After the first evaluation, one month postoperatively, participants are randomized to either a higher (2.5) or a lower (1.0) opening pressure, ratio 1:1. The opening pressure setting is blinded both for patients and the clinician during the subsequent clinical evaluations. At two months, the opening pressure is crossed over to the alternative setting (2.5 or 1.0). At three months, all participants receive the lowest shunt opening pressure (0.5) with the final evaluation the next day. Semiautomatic measurement of the lateral as well as the third cerebral ventricles will be performed using the MRI scans and volumetric software: SyMRI (SyntheticMR AB, Linköping, Sweden) CSF is collected at three times for each participant, from the lumbar spine pre- and 3 months postoperatively and intracranially during surgery. Further, intracranial CSF is taken through the Rickham Reservoir at the 3 months postoperative evaluation. After CSF from the participants has been collected, a single batch mass spectrometry will be performed with all the samples simultaneously. Sample size was determined to achieve 80% power for a two tailed paired t-test for a mean change in ventricular volume of 8ml, estimated from postoperative change in ventricular volume in a previous study. Hypotheses: The volume of the ventricular system in the brain decreases significantly after shunt-surgery. The ventricular volume is larger at high opening pressures compared to low opening pressures of the shunt. The decrease in ventricular volume is related to clinical outcome.

Official Title
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MRI-Volumetry in the Evaluation of Shunt Treatment for Hydrocephalus, a Randomised, Double-blind Study.

Conditions
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Hydrocephalus, Normal Pressure

Intervention / Treatment
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* Other: Ventriculoperitoneal shunt opening pressure setting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic normal pressure hydrocephalus and planned treatment with shunt surgery. Exclusion Criteria: Ongoing anticoagulation treatment Ongoing Clopidogrel treatment Mini mental state examination results of 15 or lower. Contraindications to magnetic resonance imaging.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double blinded crossover design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High initial<br>At the one month follow-up, the shunt is adjusted into a high opening pressure (2.5), which is crossed over to 1.0 at the two months follow-up. At the three months follow-up the opening pressure is set at 0.5 until the next day. | Other: Ventriculoperitoneal shunt opening pressure setting<br>* The ventriculoperitoneal shunt (Strata®) opening pressure can be changed using a magnetic tool. The possible settings are 0.5, 1.0, 1.5, 2.0, 2.5 with a higher setting number corresponding to a higher opening pressure and less drainage through the shunt. All settings are used in routine clinical practice.<br>|
| Experimental: Low initial<br>At the one month follow-up, the shunt is adjusted into a low opening pressure (1.0), which is crossed over to 2.5 at the two months follow-up. At the three months follow-up the opening pressure is set at 0.5 until the next day. | Other: Ventriculoperitoneal shunt opening pressure setting<br>* The ventriculoperitoneal shunt (Strata®) opening pressure can be changed using a magnetic tool. The possible settings are 0.5, 1.0, 1.5, 2.0, 2.5 with a higher setting number corresponding to a higher opening pressure and less drainage through the shunt. All settings are used in routine clinical practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular volume at different shunt settings (mL) | Change in ventricular volume (ml) measured by MRI | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Time of Timed Up and Go test at different shunt settings | Change in total walking time (sec) on Timed Up and Go. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Time of 10m walking test at different shunt settings | Change in total walking time (sec) on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular versus lumbar cerebrospinal fluid composition determined by mass spectrometry | Change in CSF composition from ventricular versus lumbar collection sites. Quantified with mass spectrometry and statistically compared on a protein by protein basis. | Cerebrospinal fluid is collected during diagnostic procedures before surgery, during surgery and three months and one day after surgery. | 
| Change in CSF composition after surgery determined by mass spectrometry | Change in CSF composition before versus after surgery. Quantified with mass spectrometry and statistically compared on a protein by protein basis. | Cerebrospinal fluid is collected during diagnostic procedures before surgery, during surgery and three months and one day after surgery. | 
| Number of steps of Timed Up and Go test at different shunt settings | Change in number of steps on Timed Up and Go test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Number of steps of Timed Up and Go test at different time points regardless of shunt setting | Change in number of steps on Timed Up and Go test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Number of steps on 10m walking test at different shunt settings | Change in number of steps on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Number of steps on 10m walking test at different time points regardless of shunt setting | Change in number of steps on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Time of 3m backwards walking test at different shunt settings | Change in total walking time (sec) on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Time of 3m backwards walking test at different time points regardless of shunt setting | Change in total walking time (sec) on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Number of steps on 3m backwards walking test at different shunt settings | Change in number of steps on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Number of steps on 3m backwards walking test at different time points regardless of shunt setting | Change in number of steps on 3m backwards walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Mini Mental State Examination at different shunt settings | Change in Mini Mental State Examination results. (min 0, max 30, higher is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Mini Mental State Examination at different time points regardless of shunt setting | Change in Mini Mental State Examination results. (min 0, max 30, higher is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Epworth sleepiness scale at different time points regardless of shunt setting | Change in Epworth sleepiness scale rating. (min 0, max 24, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Epworth sleepiness scale at different shunt settings | Change in Epworth sleepiness scale rating. (min 0, max 24, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Continence scale at different time points regardless of shunt setting | Change in continence scale rating. (min 1, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Continence scale at different shunt settings. | Change in continence scale rating. (min 1, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Balance scale at different shunt settings. | Change in Balance scale rating. (min 1, max 7, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Balance scale at different time points regardless of shunt setting | Change in Balance scale rating. (min 1, max 7, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Modified rankin scale at different time points regardless of shunt setting | Change in Modified rankin scale rating. (min 0, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Modified rankin scale at different shunt settings. | Change in Modified rankin scale rating. (min 0, max 6, lower is better) | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Gray matter volume at different time points regardless of shunt setting | Change in whole brain grey matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Gray matter volume at different shunt settings. | Change in whole brain grey matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| White matter volume at different time points regardless of shunt setting | Change in whole brain white matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| White matter volume at different shunt settings. | Change in whole brain white matter volume measured by MRI (mL). | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Time of Timed Up and Go test at different time points regardless of shunt setting | Change in total walking time (sec) on Timed Up and Go. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Time of 10m walking test at different time points regardless of shunt setting | Change in total walking time (sec) on 10m walking test. | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 
| Ventricular volume at different time points regardless of shunt setting (mL) | Change in ventricular volume (mL) measured by MRI | Assessed before surgery and at one, two and, three months and three months plus one day post surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ventriculoperitoneal Shunt, cerebral ventricular volume, cerebrospinal fluid