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

Umeå University

Status: Terminated

Conditions: Hydrocephalus, Normal Pressure

Treatments: Other: Change in shunt opening pressure; Other: Simulated change in shunt opening pressure

Study type: Interventional

Funder types: Other

Identifiers

NCT03076723

UMU-2016-CSFD-PC

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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43 participants in 2 patient groups

Fixed opening pressure

Sham Comparator group

Description:

The shunt opening pressure is changed to the same setting as at surgery.

Treatment:

Other: Simulated change in shunt opening pressure

Individual shunt opening pressure

Experimental group

Description:

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).

Treatment:

Other: Change in shunt opening pressure