Using Cerebrospinal Fluid Dynamics to Optimize Treatment of Idiopathic Normal Pressure Hydrocephalus

NCT ID: NCT03076723

Last Updated: 2022-05-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-13
• Study Completion Date: 2021-12-31

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.

Conditions

Hydrocephalus, Normal Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fixed opening pressure

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

Group Type: SHAM_COMPARATOR

Simulated change in shunt opening pressure

Intervention Type: OTHER

The shunt opening pressure is reset to the same setting.

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).

Group Type: EXPERIMENTAL

Change in shunt opening pressure

Intervention Type: OTHER

An individually determined change in shunt opening pressure is compared to no change in opening pressure.

Interventions

Change in shunt opening pressure

An individually determined change in shunt opening pressure is compared to no change in opening pressure.

Intervention Type: OTHER

Simulated change in shunt opening pressure

The shunt opening pressure is reset to the same setting.

Intervention Type: OTHER

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

Uppsala University Hospital

OTHER

Sponsor Role: collaborator

Kuopio University Hospital

OTHER

Sponsor Role: collaborator

Umeå University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Malm, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Umeå University Hospital

Sara Qvarlander, PhD

Role: STUDY_DIRECTOR

Umeå University

Locations

Kuopio university hospital

Kuopio, , Finland

Turku university hospital

Turku, , Finland

Sahlgrenska university hospital

Gothenburg, , Sweden

Umeå university hospital

Umeå, , Sweden

The Uppsala university hospital

Uppsala, , Sweden

Countries

Finland; Sweden

Other Identifiers

UMU-2016-CSFD-PC

Identifier Type: -

Identifier Source: org_study_id