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NCT Number: NCT06488248

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

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.

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Key information

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Neurosurgery, University Hospital of Basel

Basel, 4031, Switzerland

Location status: Recruiting

Location contact

Florian Marc Ebel, Dr. med.

CONTACT

[email protected]

+41 61 32 84296

Florian Marc Ebel, Dr. med.

PRINCIPAL_INVESTIGATOR

Jehuda Soleman, Prof. Dr. med.

SUB_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Endoscopic third ventriculostomy (ETV)

Procedure

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.

Ventriculoperitoneal shunt (VPS)

Procedure

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.

Primary outcomes

  1. idiopathic normal pressure hydrocephalus (iNPH) score

    Time frame: Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery

    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.

Secondary outcomes

  1. Level of consciousness (Glasgow Coma Scale)

    Time frame: Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery

    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.

  2. Degree of disability and dependency (modified Rankin Scale)

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    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.

  3. Cognitive function (Montreal Cognitive Assessment)

    Time frame: Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery

    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.

  4. GaitRite walkway

    Time frame: At 2 and 12 months after surgery

    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.

  5. Timed-Up-and-Go Test

    Time frame: At 2 and 12 months after surgery

    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.

  6. Modified Clinical Test of Sensory Interaction on Balance

    Time frame: At 2 and 12 months after surgery

    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.

  7. Modified Balance Error Scoring System

    Time frame: Before surgery (baseline), at 2 and 12 months after surgery

    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.

  8. 5-times-sit-to-stand test

    Time frame: At 2 and 12 months after surgery

    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.

  9. Hand grip strength test

    Time frame: At 2 and 12 months after surgery

    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.

  10. Montreal Cognitive Assessment

    Time frame: At 2 and 12 months after surgery

    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.

  11. Test of Attentional Performance

    Time frame: At 2 and 12 months after surgery

    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.

  12. Trail Making Test

    Time frame: At 2 and 12 months after surgery

    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.

  13. Stroop-Test

    Time frame: At 2 and 12 months after surgery

    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.

  14. CERAD Word List

    Time frame: At 2 and 12 months after surgery

    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.

  15. CERAD Constructive Praxis

    Time frame: At 2 and 12 months after surgery

    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.

  16. Boston Naming Test

    Time frame: At 2 and 12 months after surgery

    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.

  17. Rey-Osterrieth Complex Figure Test

    Time frame: At 2 and 12 months after surgery

    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.

  18. Intensity of depression (Beck Depression Inventory)

    Time frame: Before surgery (baseline), at 2 and 12 months after surgery

    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.

  19. Flow-void presence

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    In a radiological assessment the flow-void presence is determined.

  20. Ventricular volumetry

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    In a radiological assessment the ventricular volumetry is measured.

  21. Periventricular perfusion measurements

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    In a radiological assessment periventricular perfusion measurements are carried out.

  22. iNPH Radiological Scale

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    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.

  23. iNPH severity

    Time frame: Before surgery (baseline), up to 5 days, 2, 6, and 12 months after surgery

    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.

  24. Health-related quality of life

    Time frame: At 2, 6, and 12 months after surgery

    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.

  25. Evaluation of complications

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    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).

  26. Evaluation of revision surgery

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    during hospitalization, 6-8 weeks, as well as 6- and 12-month follow-up, the incidence and reason of revision surgery is assessed.

  27. Mortality

    Time frame: Up to 5 days, 2, 6, and 12 months after surgery

    The mortality is assessed during hospitalization and the 12-month follow-up

Study contacts

Contact information is provided by the study sponsor or research team.

Florian Marc Ebel, Dr. med.

CONTACT

[email protected]

+41 61 32 84296

Raphael Guzman, Prof. Dr. med.

CONTACT

[email protected]

+41 61 32 87522

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Jul 5, 2024
Registry last updated
Feb 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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