Using Cerebrospinal Fluid Dynamics to Optimize Treatment of Idiopathic Normal Pressure Hydrocephalus (PULSE-OPT)

Using Cerebrospinal Fluid Dynamics to Identify Shunt Responders in Idiopathic Normal Pressure Hydrocephalus and to Optimize Postoperative Clinical Improvement While Minimizing Overdrainage Related Complications - A Double Blind Randomized Study

The purpose of the study is to determine if the so called pulsatility curve, which describes the relationship between intracranial pressure (ICP) and ICP pulsatility, can be used to predict outcome of treatment, in the form of shunt surgery, in idiopathic normal pressure hydrocephalus (INPH) and to guide the adjustment of shunt opening pressure after the surgery. The main hypotheses of the study are:

1. The pulsatility curve may be the best auxiliary test to predict shunt surgery outcome in INPH patients. With a "fixed" shunt opening pressure, the preoperatively assessed potential pulse amplitude reduction (determined by analysis of the pulsatility curve) predicts postoperative improvement in gait velocity and cognitive functions.
2. A postoperative pulsatility curve can be used to further optimize ICP pulsatility by guiding opening pressure adjustment. Shunt adjustment based on the pulsatility curve three months postoperatively will increase improvement, but not complications, compared to a shunt with "fixed" opening pressure.

Based on these hypotheses, three specific aims for the study have been defined:

1. To determine if improvement three month after surgery is associated with postoperative reduction in pulse amplitude.
2. To determine if a pulsatility curve obtained preoperatively can predict improvement in gait velocity and cognitive functions in INPH patients three months after surgery.
3. To compare outcome six months after surgery and complications rates between INPH patients with a "fixed" opening pressure versus those where the shunt has been adjusted based on the pulsatility curve, three months after the shunt insertion.

Study Overview

• Status: Terminated
• Conditions: Hydrocephalus, Normal Pressure
• Intervention / Treatment: Other: Simulated change in shunt opening pressure; Other: Change in shunt opening pressure

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Kuopio, Finland, 70210
    • Kuopio University Hospital
  • Turku, Finland, 20521
    • Turku University Hospital
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
  • Umeå, Sweden, 90185
    • Umeå University Hospital
  • Uppsala, Sweden, 75185
    • The Uppsala university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Possible or probable INPH according to the INPH guidelines.
• Symptom duration ≥ 3 months
• Age ≥50 years
• Able to walk 10 meters with or without an assistant device.

• Decision to recommend shunt surgery based either on:

  • Improvement after cerebrospinal fluid (CSF) tap (i.e. positive tap test), or;
  • Increased CSF outflow resistance, or;
  • A combination of "typical" signs/symptoms + "typical" MRI findings;
  • A combination of a-c.

Exclusion Criteria:

• NPH due to hemorrhage, meningitis or stroke (secondary NPH).
• Symptom duration ≥ 5 years.
• Patients considered surgical risk.
• Baseline gait velocity >1.1 m/sec (60 m/min) without assistant device
• Mini Mental State Exam score ≤ 20 points.
• Musculoskeletal condition precluding gait assessment.
• Severe hearing or visual impairment
• Medication in the form of warfarin or novel oral anticoagulant (NOAC)
• Insufficient pressure data below resting pressure during the CSF infusion investigation, i.e. no complete assessment of the pulsatility curve

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: Fixed opening pressure; The shunt opening pressure is changed to the same setting as at surgery.	Other: Simulated change in shunt opening pressure; The shunt opening pressure is reset to the same setting.
EXPERIMENTAL: Individual shunt opening pressure; The shunt opening pressure is adjusted (up one step, down one step or unchanged) according to an individual analysis of the pulsatility curve (as assessed after shunt surgery).	Other: Change in shunt opening pressure; An individually determined change in shunt opening pressure is compared to no change in opening pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total score on European INPH scale	scale describing the cardinal symptoms of INPH	3 and 6 months after surgery
Gait velocity	Maximal gait velocity (3 x 10 m)	3 and 6 months after surgery
European INPH scale	Change in total score on scale describing the cardinal symptoms of INPH	baseline (before surgery) and 3 months after surgery
Gait velocity	Maximal gait velocity (3 x 10 m)	baseline (before surgery) and 3 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Computerized General Neuropsychological INPH Test (CoGNIT)	A computerized neuropsychological test battery for use in INPH, which produces a total "neuropsychological" score	baseline (before surgery) and 3 months after surgery
Timed up and go test	Mobility test: rise from chair, walk 3 m, turn around, walk back and sit down again	baseline (before surgery) and 3 months after surgery
EuroQoL's (EQ) standardized 5 dimensions (5D) 5 levels (5L) instrument (EQ-5D-5L™)	EuroQoL's standardized instrument for health outcome, which assesses health in 5 dimensions, on 5 levels	baseline (before surgery) and 3 months after surgery
Urogenital Distress Inventory (UDI-6)	Continence assessment scale	baseline (before surgery) and 3 months after surgery
Incontinence Impact Questionnaire, Short Form (IIQ-7)	Continence assessment scale	baseline (before surgery) and 3 months after surgery
Barthel Index	Activities of daily living assessment scale	baseline (before surgery) and 3 months after surgery
Modified Rankin scale	Disability assessment scale	baseline (before surgery) and 3 months after surgery
Geriatric depression scale (GDS-15)	Score on a geriatric depression scale consisting of 15 yes/no questions	baseline (before surgery) and 3 months after surgery
Mini-mental state examination (MMSE) score	Score on the MMSE scale (general mental status)	baseline (before surgery) and 3 months after surgery

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Kuopio University Hospital; Sahlgrenska University Hospital, Sweden; Uppsala University Hospital
• Investigators: Principal Investigator: Jan Malm, MD, PhD, Umeå University Hospital; Study Director: Sara Qvarlander, PhD, Umea University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 13, 2017
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): December 31, 2021

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: March 9, 2017
• First Posted (ACTUAL): March 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: UMU-2016-CSFD-PC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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