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MRI-Volumetry in the Evaluation of Shunt Treatment for Hydrocephalus

Not Applicable
Completed
Conditions
Hydrocephalus, Normal Pressure
Interventions
Other: Ventriculoperitoneal shunt opening pressure setting
Registration Number
NCT04599153
Lead Sponsor
Uppsala University
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Low initialVentriculoperitoneal shunt opening pressure settingAt 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.
High initialVentriculoperitoneal shunt opening pressure settingAt 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.
Primary Outcome Measures
NameTimeMethod
Time of "Timed Up and Go" test at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in total walking time (sec) on "Timed Up and Go".

Ventricular volume at different shunt settings (mL)Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in ventricular volume (ml) measured by MRI

Time of 10m walking test at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in total walking time (sec) on 10m walking test.

Secondary Outcome Measures
NameTimeMethod
Time of 3m backwards walking test at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in total walking time (sec) on 3m backwards walking test.

Number of steps on 3m backwards walking test at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in number of steps on 3m backwards walking test.

Continence scale at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in continence scale rating. (min 1, max 6, lower is better)

Number of steps of "Timed Up and Go" test at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in number of steps on "Timed Up and Go" test.

Ventricular versus lumbar cerebrospinal fluid composition determined by mass spectrometryCerebrospinal fluid is collected during diagnostic procedures before surgery, during surgery and three months and one day after surgery.

Change in CSF composition from ventricular versus lumbar collection sites. Quantified with mass spectrometry and statistically compared on a protein by protein basis.

Number of steps on 10m walking test at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in number of steps on 10m walking test.

Change in CSF composition after surgery determined by mass spectrometryCerebrospinal fluid is collected during diagnostic procedures before surgery, during surgery and three months and one day after surgery.

Change in CSF composition before versus after surgery. Quantified with mass spectrometry and statistically compared on a protein by protein basis.

Time of 3m backwards walking test at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in total walking time (sec) on 3m backwards walking test.

Number of steps of "Timed Up and Go" test at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in number of steps on "Timed Up and Go" test.

Number of steps on 10m walking test at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in number of steps on 10m walking test.

Number of steps on 3m backwards walking test at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in number of steps on 3m backwards walking test.

Mini Mental State Examination at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Mini Mental State Examination results. (min 0, max 30, higher is better)

Mini Mental State Examination at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Mini Mental State Examination results. (min 0, max 30, higher is better)

Continence scale at different shunt settings.Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in continence scale rating. (min 1, max 6, lower is better)

Balance scale at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Balance scale rating. (min 1, max 7, lower is better)

Gray matter volume at different shunt settings.Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in whole brain grey matter volume measured by MRI (mL).

Balance scale at different shunt settings.Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Balance scale rating. (min 1, max 7, lower is better)

Epworth sleepiness scale at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Epworth sleepiness scale rating. (min 0, max 24, lower is better)

Epworth sleepiness scale at different shunt settingsAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Epworth sleepiness scale rating. (min 0, max 24, lower is better)

Time of 10m walking test at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in total walking time (sec) on 10m walking test.

Modified rankin scale at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Modified rankin scale rating. (min 0, max 6, lower is better)

Modified rankin scale at different shunt settings.Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in Modified rankin scale rating. (min 0, max 6, lower is better)

Gray matter volume at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in whole brain grey matter volume measured by MRI (mL).

Time of "Timed Up and Go" test at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in total walking time (sec) on "Timed Up and Go".

White matter volume at different time points regardless of shunt settingAssessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in whole brain white matter volume measured by MRI (mL).

White matter volume at different shunt settings.Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in whole brain white matter volume measured by MRI (mL).

Ventricular volume at different time points regardless of shunt setting (mL)Assessed before surgery and at one, two and, three months and three months plus one day post surgery.

Change in ventricular volume (mL) measured by MRI

Trial Locations

Locations (1)

Neurology Clinic, Östersund Hospital

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Östersund, Jämtland, Sweden

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