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

NCT03076723 | Terminated

• 1 other identifier: UMU-2016-CSFD-PC
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 5

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. 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. 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.
3. 3.To determine if improvement three month after surgery is associated with postoperative reduction in pulse amplitude.
4. 4.To determine if a pulsatility curve obtained preoperatively can predict improvement in gait velocity and cognitive functions in INPH patients three months after surgery.
5. 5.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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (9)

• Computerized General Neuropsychological INPH Test (CoGNIT)

  baseline (before surgery) and 3 months after surgery

• Timed up and go test

  baseline (before surgery) and 3 months after surgery

• EuroQoL's (EQ) standardized 5 dimensions (5D) 5 levels (5L) instrument (EQ-5D-5L™)

  baseline (before surgery) and 3 months after surgery

• Urogenital Distress Inventory (UDI-6)

  baseline (before surgery) and 3 months after surgery

• Incontinence Impact Questionnaire, Short Form (IIQ-7)

  baseline (before surgery) and 3 months after surgery

Study Arms (2)

Fixed opening pressure

SHAM COMPARATOR

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

Other: Simulated change in shunt opening pressure

Individual shunt opening pressure

EXPERIMENTAL

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

Interventions

Change in shunt opening pressure OTHER

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

Individual shunt opening pressure

Simulated change in shunt opening pressure OTHER

The shunt opening pressure is reset to the same setting.

Fixed opening pressure

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Umeå University: lead
• Sahlgrenska University Hospital: collaborator
• Uppsala University Hospital: collaborator
• Kuopio University Hospital: collaborator

Study Sites (5)

Kuopio university hospital

Kuopio, 70210, Finland

Location

Turku university hospital

Turku, 20521, Finland

Location

Sahlgrenska university hospital

Gothenburg, 41345, Sweden

Location

Umeå university hospital

Umeå, 90185, Sweden

Location

The Uppsala university hospital

Uppsala, 75185, Sweden

Location

MeSH Terms

Conditions

Hydrocephalus, Normal Pressure

Condition Hierarchy (Ancestors)

Hydrocephalus; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Jan Malm, MD, PhD

  Umeå University Hospital

  PRINCIPAL INVESTIGATOR

• Sara Qvarlander, PhD

  Umeå University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: March 10, 2017
• Study Start: June 13, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2); SE (3)