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

Hydrocephalus, Normal Pressure Clinical Trial

— PULSE-OPT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03076723
• Other study ID #: UMU-2016-CSFD-PC
• Status: Terminated
• Phase: N/A
• Start date: June 13, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: May 2022
• Source: Umeå University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hydrocephalus
• Hydrocephalus, Normal Pressure

Intervention

Other:
• Change in shunt opening pressure
An individually determined change in shunt opening pressure is compared to no change in opening pressure.
• Simulated change in shunt opening pressure
The shunt opening pressure is reset to the same setting.

Locations

Country	Name	City	State
Finland	Kuopio university hospital	Kuopio
Finland	Turku university hospital	Turku
Sweden	Sahlgrenska university hospital	Gothenburg
Sweden	Umeå university hospital	Umeå
Sweden	The Uppsala university hospital	Uppsala

Sponsors (4)

Lead Sponsor	Collaborator
Umeå University	Kuopio University Hospital, Sahlgrenska University Hospital, Sweden, Uppsala University Hospital

Countries where clinical trial is conducted

Finland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in total score on European INPH scale	scale describing the cardinal symptoms of INPH	3 and 6 months after surgery
Primary	Gait velocity	Maximal gait velocity (3 x 10 m)	3 and 6 months after surgery
Primary	European INPH scale	Change in total score on scale describing the cardinal symptoms of INPH	baseline (before surgery) and 3 months after surgery
Primary	Gait velocity	Maximal gait velocity (3 x 10 m)	baseline (before surgery) and 3 months after surgery
Secondary	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
Secondary	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
Secondary	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
Secondary	Urogenital Distress Inventory (UDI-6)	Continence assessment scale	baseline (before surgery) and 3 months after surgery
Secondary	Incontinence Impact Questionnaire, Short Form (IIQ-7)	Continence assessment scale	baseline (before surgery) and 3 months after surgery
Secondary	Barthel Index	Activities of daily living assessment scale	baseline (before surgery) and 3 months after surgery
Secondary	Modified Rankin scale	Disability assessment scale	baseline (before surgery) and 3 months after surgery
Secondary	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
Secondary	Mini-mental state examination (MMSE) score	Score on the MMSE scale (general mental status)	baseline (before surgery) and 3 months after surgery