Clinical trial NCT03076723: Using Cerebrospinal Fluid Dynamics to Optimize Treatment of Idiopathic Normal Pressure Hydrocephalus
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hydrocephalus, Normal Pressure
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Sahlgrenska University Hospital
name: Uppsala University Hospital
name: Kuopio University Hospital
First posted: 2017-03-10
Enrollment: 43
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in total score on European INPH scale
timeFrame: 3 and 6 months after surgery
measure: Gait velocity
timeFrame: 3 and 6 months after surgery
measure: European INPH scale
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Gait velocity
timeFrame: baseline (before surgery) and 3 months after surgery
Secondary outcomes:
measure: Computerized General Neuropsychological INPH Test (CoGNIT)
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Timed up and go test
timeFrame: baseline (before surgery) and 3 months after surgery
measure: EuroQoL's (EQ) standardized 5 dimensions (5D) 5 levels (5L) instrument (EQ-5D-5L™)
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Urogenital Distress Inventory (UDI-6)
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Incontinence Impact Questionnaire, Short Form (IIQ-7)
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Barthel Index
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Modified Rankin scale
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Geriatric depression scale (GDS-15)
timeFrame: baseline (before surgery) and 3 months after surgery
measure: Mini-mental state examination (MMSE) score
timeFrame: baseline (before surgery) and 3 months after surgery
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: Kuopio university hospital
city: Turku
country: Finland
facility: Turku university hospital
city: Gothenburg
country: Sweden
facility: Sahlgrenska university hospital
city: Umeå
country: Sweden
facility: Umeå university hospital
city: Uppsala
country: Sweden
facility: The Uppsala university hospital
Study officials:
affiliation: Umeå University Hospital
name: Jan Malm, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Umeå University
name: Sara Qvarlander, PhD
role: STUDY_DIRECTOR
References: