- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01570257
A Trial of High and Low Pressure Level Settings on a Programmable Ventriculoperitoneal Shunt Valve for Idiopathic Normal Pressure Hydrocephalus
A Randomized Trial of High and Low Pressure Level Settings on a Programmable Ventriculoperitoneal Shunt Valve for Idiopathic Normal Pressure Hydrocephalus. Results of the Dutch Evaluation Program Strata Shunt (DEPSS) Trial
Study Overview
Status
Conditions
Detailed Description
Idiopathic normal pressure hydrocephalus (INPH) is characterized by a clinical triad of symptoms: gait disturbance, urinary incontinence and cognitive impairment. INPH typically develops among the elderly and shares some symptoms with other neurological disorders. In general, 60-70% of patients with the complete clinical triad and signs of hydrocephalus on CT/MRI will improve after cerebrospinal fluid (CSF) shunting. Implantation of a shunt, however, carries complications such as infection, obstruction, underdrainage, and overdrainage. The cumulative complication rate and revision rate is estimated to be 35-80% among adults. The England shunt registry described an overall incidence of underdrainage of 52%, and studies have resulted in incidences of overdrainage between 2 and 21%. Børgesen claims that 80% of complications of shunting for INPH are related to overdrainage. Overdrainage may lead to low intracranial pressure syndrome and subdural effusions (SDE). Low intracranial pressure syndrome is characterized by orthostatic headaches and sometimes nausea, vomiting, drowsiness, diplopia, upward gaze palsy and visual defects. As INPH patients are often elderly patients with concomitant brain atrophy and normal CSF pressure they are especially at risk for developing signs and symptoms of overdrainage.
Overdrainage can be prevented or treated by implanting an anti-siphon device (ASD) or changing the opening pressure of the valve (OPV). Different ASDs have been developed since the first publication in 1973. They have in common that the lumen of the catheter is closed under influence of a negative hydrostatic pressure at the level of the ASD. The optimal valve setting for treating INPH is still the subject of controversy. The dilemma in INPH patients is that a low OPV might lead to overdrainage-related symptoms. A high valve setting might lead to underdrainage and the patient misses the chance of maximum improvement.
Studies examining whether to use a low or high OPV have been contradictory so far.
After randomization, baseline primary and secondary outcome measure assessments are conducted preoperatively. Within 24 hours of shunting, skull, thoracic, and abdominal X-rays are done to verify device connections and position. Follow-up visits at 1, 3, and 9 months include all primary and secondary outcome assessments. All measurements are done by a research assistant who visits the participating hospitals to prevent inter-observer variation. Study end for each patient is defined as completing the 9 month visit or death, detection of SDE on CT, or shunt removal or revision due to infection or dysfunction.
The PL in Group 1 (control group) is allowed to be increased to a higher setting when an SDE is detected. The patient thereby reaches study end, and the treating physician is free to decide how to manage the PL. The 9-month follow-up is still obtained. The PL in Group 2 is preset at the highest PL and eventually lowered 1 step at each follow-up visit when the modified mini mental state (3MS) or Gait score is not increased ≥ 15% provided that no SDE is visible on a new CT scan. The 15% is considered the minimum percentage to reliably determine improvement.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Zuid Holland
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Rotterdam, Zuid Holland, Netherlands, 3015 CA
- Erasmus Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
At least two out of three of the typical signs of normal pressure hydrocephalus:
- gait disturbance,
- cognitive impairment and
- urinary incontinence.
- Radiological verification of a communicating hydrocephalus.
- Cerebrospinal fluid pressure at lumbar puncture < 150 mm H2O.
Exclusion Criteria:
- Aqueduct stenosis.
- Severe comorbidity.
- Age > 85 years.
- Possibly confounding neurological diseases.
- Recent meningitis or subarachnoid hemorrhage.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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No Intervention: control group
These patients receive a shunt with the valve preset and fixed at a Performance level of 1.0, corresponding to an opening/closing pressure of 35-55 mm H2O.
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Experimental: Intervention group
These patients receive a shunt with the valve preset at a Performance level (PL) of 2.5, corresponding to an opening/closing pressure of 135-155 mm H2O.
The PL is allowed to be lowered until clinical improvement occurs.
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in the intervention group, the performance level(PL) of the valve of the VP shunt, preset at the highest PL (meaning highest resistance) is lowered stepwise in the follow-up period at 1,3 and 9 months postoperatively after implantation until improvement occurs or signs of overdrainage are encountered on a new CT scan of the brain.
In the control group the PL is preset and fixed at the second lowest PL and these patients serve as a control group.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
the number of Subdural effusions, detected on CT scan, in patients showing clinical improvement after implantation of a ventriculoperitoneal shunt,at the end of the study
Time Frame: baseline and 9 months (end of study)
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the most important parameter of the study will be the difference in incidence of subdural effusions between both groups
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baseline and 9 months (end of study)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
the final performance level of the valve of the shunt at the end of the study
Time Frame: baseline and 9 months (end of study)
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Peformance level is the opening/closing pressure of the valve and reflects the hydrostatic resistance of the valve of the shunt
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baseline and 9 months (end of study)
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change in gait score
Time Frame: baseline and 9 months (end of study)
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baseline and 9 months (end of study)
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change in urinary incontinence
Time Frame: baseline and 9 months (end of study)
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baseline and 9 months (end of study)
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change in modified mini mental state (3MS) score
Time Frame: baseline and 9 months (end of study)
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the 3MS score quantifies cognitive function
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baseline and 9 months (end of study)
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change in modified Rankin (mRS) score
Time Frame: baseline and 9 months (end of study)
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the mRS quantifies functional impairment
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baseline and 9 months (end of study)
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change in Evans' ratio
Time Frame: baseline and 9 months (end of study)
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a measure of ventricular width, on CT scan
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baseline and 9 months (end of study)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Clemens MF Dirven, Prof. PhD, Erasmus Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MEC 03.1073
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Idiopathic Normal Pressure Hydrocephalus
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Umeå UniversityCompleted
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