Endoscopic Third Ventriculostomy vs. Ventriculoperitoneal Shunt in Idiopathic Normal Pressure Hydrocephalus (ENDOVEST)

Endoscopic Third Ventriculostomy Compared to Ventriculoperitoneal Shunt as Treatment for Idiopathic Normal Pressure Hydrocephalus (ENDOVEST): A Randomized Trial

The aim of this single-center, two-arm, open-labeled, randomized controlled clinical study is to compare two surgical interventions, endoscopic third ventriculostomy and ventriculoperitoneal shunt, in treating idiopathic normal pressure hydrocephalus in terms of clinical improvement.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Normal Pressure Hydrocephalus (INPH)
• Intervention / Treatment: Procedure: Endoscopic third ventriculostomy (ETV); Procedure: Ventriculoperitoneal shunt (VPS)

Detailed Description

Idiopathic normal pressure hydrocephalus (iNPH) primarily affects elderly individuals, with prevalence rates of approximately 1.4% among those over 65 years and 5.9% among those over 80 years old. It is characterized by fluid buildup in the brain with normal cerebrospinal fluid pressure and is unique among neurodegenerative disorders in its potential for successful treatment. Common symptoms include difficulty walking, urinary incontinence, and cognitive decline, which significantly impact quality of life.

The standard treatment involves inserting a ventriculoperitoneal shunt (VPS) to drain cerebrospinal fluid, achieving a 75% success rate in improving symptoms. However, VPS has a drawback: a high rate of revision surgery (approximately 18% during follow-up). An alternative treatment is endoscopic third ventriculostomy (ETV), which avoids placing foreign materials and thus eliminates risks associated with shunt malfunction and infections. ETV is an established neuroendoscopic procedure mainly used to treat non-communicating hydrocephalus, typically due to aqueduct stenosis.

This study aims to compare ETV and VPS for the treatment of iNPH to investigate whether ETV leads to fewer complications while achieving a comparable rate of postoperative symptom improvement.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florian Marc Ebel, Dr. med.; Phone Number: +41 61 32 84296; Email: florianmarc.ebel@usb.ch
• Study Contact Backup: Name: Raphael Guzman, Prof. Dr. med.; Phone Number: +41 61 32 87522; Email: raphael.guzman@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Department of Neurosurgery, University Hospital of Basel
    • Contact: Florian Marc Ebel, Dr. med.; Phone Number: +41 61 32 84296; Email: florianmarc.ebel@usb.ch
    • Principal Investigator: Florian Marc Ebel, Dr. med.
    • Sub-Investigator: Jehuda Soleman, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• >40 years of age
• Symptom duration ≥3 months, <24 months
• No antecedent head trauma, ICH, meningitis, or other cause of secondary hydrocephalus
• MUST show gait/balance disturbance, PLUS cognition impairment AND/OR urinary dysfunction.
• Ventricular enlargement (Evans Index > 0.3) not attributable to cerebral atrophy or congenital enlargement
• No macroscopic obstruction to cerebrospinal fluid (CSF) flow Spinal Tap-Test
• Opening pressure (on lateral decubitus): <24cmH2O
• Clinical improvement in at least one of the main symptoms after 40-50ml withdrawal of CSF

Exclusion Criteria:

• ≤40 years of age
• No informed consent
• Other neurologic, psychiatric or general medical condition which is sufficient to explain the presenting symptoms.
• Previous cranial neurosurgical interventions
• Other associated dementia syndromes
• Incapacity to walk
• Pregnancy and breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endoscopic third ventriculostomy (ETV) group; The investigational group undergoes endoscopic third ventriculostomy (ETV) for the treatment of idiopathic normal pressure hydrocephalus (iNPH).	Procedure: Endoscopic third ventriculostomy (ETV); The procedure is performed using an endoscope (LOTTA® system, Karl Storz Endoscopes, Germany; Minop®, BBraun, Tuttlingen, Germany or equivalent). The intervention is carried out under general anesthesia, with the procedure typically lasting around 60 minutes.
Other: Ventriculoperitoneal shunt (VPS) group; The control group undergoes ventriculoperitoneal shunt (VPS) implantation for the treatment of iNPH.	Procedure: Ventriculoperitoneal shunt (VPS); The procedure entails the insertion of a catheter into both the ventricular system and the peritoneal cavity, connected to a programmable valve that regulates cerebrospinal fluid flow. The choice of programmable valve (Codman Hakim or Codman Certas Programmable Valves, Integra, Plainsboro, USA; Strata valve, Medtronic, Minneapolis, USA; Sophysa, Orsay, France; Miethke proGAV, Aesculap, Tuttlingen, Germany) is at the surgeon's discretion. The preoperative valve setting is preset to a pressure level between 85 - 135 mmH2O. The VPS procedure is conducted under general anesthesia and typically lasts approximately 90-120 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
idiopathic normal pressure hydrocephalus (iNPH) score	The idiopathic normal pressure hydrocephalus (iNPH) score is used to measure the clinical improvement and complication rate. The iNPH score evaluates the three cardinal symptoms of iNPH-gait disturbance, dementia, and urinary incontinence-with each category assigned a score between 0 and 4 based on severity, resulting in a total score ranging from 0 (indicating normal) to 12 (reflecting the maximum severity of symptoms The score will be assessed during the outpatient consultation before surgery, at admission directly preceding surgery, and postoperatively at discharge, as well as during follow-up at 6-8 weeks, 6 months, and 12 months after the operation.	Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of disability and dependency (modified Rankin Scale)	The modified Rankin Scale (mRS) is used to assess the degree of disability and dependency in everyday life. Th mRS is a standard tool to assess the neurological outcome in trials with acute severe brain disease. The mRS ranges from 0 (no disability) to 6 (death). Lower values indicate less disability.	Up to 5 days, 2, 6, and 12 months after surgery
GaitRite walkway	To assess the gait and balance, a 10-metre GaitRite walkway, specifically designed to measure and analyze gait patterns, is performed. The body's movement are recorded using the the Ambulatory Parkinson's Disease Monitoring (APDM) Mobility Lab System.	At 2 and 12 months after surgery
Timed-Up-and-Go Test	To assess the gait and balance, the Timed-Up-and-Go Test is performed. This is a simple and quick assessment to measure the time taken for an individual to stand up from a chair, walk three meters, turn around, walk back to the chair, and sit down again, with shorter times indicating better mobility.	At 2 and 12 months after surgery
Modified Clinical Test of Sensory Interaction on Balance	To assess the gait and balance, the modified Clinical Test of Sensory Interaction on Balance (mCTSIB, 30 seconds) is performed. The mCTSIB measures a person's ability to maintain stability in different sensory conditions for 30 seconds each.	At 2 and 12 months after surgery
5-times-sit-to-stand test	To assess the gait and balance, the 5-times-sit-to-stand test is performed. It involves timing how long it takes a person to rise from a seated position to a standing position five times as quickly as possible.	At 2 and 12 months after surgery
Hand grip strength test	To assess the gait and balance, the hand grip strength test is performed. It assesses the maximum isometric strength of the hand and forearm muscles and involves using a dynamometer to measure the force exerted when a person squeezes the device with their hand.	At 2 and 12 months after surgery
Montreal Cognitive Assessment	As a neuropsychological assessment the Montreal Cognitive Assessment is performed to evaluate cognitive function and detect mild cognitive impairment. It assesses various cognitive domains, including memory, attention, language, and executive functions, with a maximum score of 30 points; higher scores indicate better cognitive function.	At 2 and 12 months after surgery
Test of Attentional Performance	As a neuropsychological assessment the TAP Test (Test of Attentional Performance) is a computer-based assessment used to evaluate different aspects of attention, such as alertness, divided attention, and sustained attention. It measures reaction times and accuracy across various tasks designed to assess cognitive functions related to attentional control and processing speed.	At 2 and 12 months after surgery
Trail Making Test	As a neuropsychological assessment the Trail Making Test is performed to evaluate cognitive flexibility, visual attention, and task-switching abilities. It consists of two parts: Part A involves connecting numbered circles sequentially, while Part B requires alternating between numbers and letters in ascending order. The test measures executive functioning and processing speed, with longer completion times indicating potential cognitive impairment.	At 2 and 12 months after surgery
Stroop-Test	As a neuropsychological assessment the Stroop-Test is performed to measure selective attention, cognitive flexibility, and processing speed. It typically involves presenting color names (e.g., "red," "blue") printed in incongruent colored ink (e.g., the word "red" printed in blue ink), and participants are required to name the ink color while ignoring the word. The test assesses the ability to inhibit automatic responses and is sensitive to cognitive impairments, with longer response times or increased errors indicating potential difficulties in executive functioning.	At 2 and 12 months after surgery
CERAD Word List	The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List is used as a neuropsychological assessment to evaluate verbal memory. It consists of a list of 10 common words that the participant is asked to recall immediately after hearing them. This test assesses the ability to remember and retrieve information shortly after it was presented, providing insights into memory function and potential cognitive impairments.	At 2 and 12 months after surgery
CERAD Constructive Praxis	The CERAD Constructive Praxis is used as a neuropsychological assessment to assess visuospatial and constructional abilities by asking participants to copy a series of geometric figures. This test helps evaluate visual perception, spatial orientation, and motor skills, providing insights into cognitive functioning.	At 2 and 12 months after surgery
Boston Naming Test	As a neuropsychological assessment the Boston Naming Test is performed. It assesses the ability to name objects or pictures presented by the examiner, evaluating language and semantic memory functions.	At 2 and 12 months after surgery
Rey-Osterrieth Complex Figure Test	As a neuropsychological assessment the Rey-Osterrieth Complex Figure Test is performed. It assesses visuospatial and constructional abilities as well as visual memory. It involves copying a complex figure and then recalling and reproducing it from memory.	At 2 and 12 months after surgery
Flow-void presence	In a radiological assessment the flow-void presence is determined.	Up to 5 days, 2, 6, and 12 months after surgery
Ventricular volumetry	In a radiological assessment the ventricular volumetry is measured.	Up to 5 days, 2, 6, and 12 months after surgery
Periventricular perfusion measurements	In a radiological assessment periventricular perfusion measurements are carried out.	Up to 5 days, 2, 6, and 12 months after surgery
iNPH Radiological Scale	In a radiological assessment the idiopathic normal pressure hydrocephalus (iNPH) radiological scale is assessed. Scores typically range from 0 to 12, with higher scores indicating greater severity of radiological findings suggestive of iNPH, such as enlarged ventricles, narrow sulci, and periventricular white matter changes.	Up to 5 days, 2, 6, and 12 months after surgery
Health-related quality of life	The quality of life is assessed using the 15D health-related quality of life (HRQoL) patient-reported questionnaire. It cover aspects like physical functioning, emotional well-being, social functioning, and pain. Scores can range from 0 to 100, with higher scores reflecting better perceived health and functioning across various domains, while lower scores suggest greater impairment and reduced quality of life.	At 2, 6, and 12 months after surgery
Evaluation of complications	During hospitalization, 6-8 weeks, as well as 6- and 12-month follow-up, the incidence of complications is assessed. Complications are defined as infections, bleeding, shunt dysfunction (e.g., due to misplacement, obstruction of the proximal ventricular catheter, dysfunction of the valve, dysfunction of the peritoneal catheter), ETV occlusions (requiring re-ETV or VPS insertion), and neuronal tissue injury (e.g., fornix injury).	Up to 5 days, 2, 6, and 12 months after surgery
Evaluation of revision surgery	during hospitalization, 6-8 weeks, as well as 6- and 12-month follow-up, the incidence and reason of revision surgery is assessed.	Up to 5 days, 2, 6, and 12 months after surgery
Mortality	The mortality is assessed during hospitalization and the 12-month follow-up	Up to 5 days, 2, 6, and 12 months after surgery
Level of consciousness (Glasgow Coma Scale)	The Glasgow Coma Scale (GCS) is used to assess the level of consciousness by evaluating eye, verbal, and motor responses. The GCS score ranges from 3 to 15, with higher scores indicating better neurological function and a less severe brain injury. A score of 3 represents deep unconsciousness, while a score of 15 indicates full alertness and orientation.	Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery
Cognitive function (Montreal Cognitive Assessment)	The Montreal Cognitive Assessment (MoCA) is used to evaluate cognitive function and detect mild cognitive impairment. It scores between 0 and 30, with higher scores indicating better cognitive performance. A score of 26 or above is generally considered normal.	Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery
Modified Balance Error Scoring System	To assess the gait and balance, the modified Balance Error Scoring System (mBESS) is performed. The mBESS involves performing three standing balance tasks (double-leg stance, single-leg stance, and tandem stance) on both firm and foam surfaces, with errors recorded to gauge balance performance.	Before surgery (baseline), at 2 and 12 months after surgery
Intensity of depression (Beck Depression Inventory)	The Beck Depression Inventory (BDI) is used to assess the intensity of depression. The BDI is a self-report questionnaire designed to assess the severity of depressive symptoms. It consists of 21 multiple-choice questions, each related to a specific symptom of depression such as sadness, pessimism, guilt, and fatigue. Scores on the BDI can range from 0 to 63, with higher scores indicating more severe depressive symptoms.	Before surgery (baseline), at 2 and 12 months after surgery
iNPH severity	iNPH severity is measured using the Hellström score, which ranges from 0 to 12, with higher scores indicating more severe symptoms across domains of gait, balance, and cognitive impairment.	Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Florian Marc Ebel, Dr. med., Department of Neurosurgery, University Hospital of Basel

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Neurosurgery; Surgical treatment; Endoscopic third ventriculostomy (ETV); Ventriculoperitoneal shunt (VPS)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: 2024-00845; ko23Soleman

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No