European Study of Prodromal iNPH

NCT05910944 | Recruiting

• 1 other identifier: STOP iNPH
• Study Type: observational
• Target: 140
• Locations: 3 countries
• Sites: 7

Brief Summary

To investigate if progression from prodromal into symptomatic NPH can be predicted from advanced neuroimaging, biomarkers in cerebrospinal fluid (CSF) and plasma and investigate the unknown mechanisms causing deterioration by investigating longitudinal changes in the above-mentioned variables. Three different cohorts with both asymptomatic and symptomatic patients as well as healthy controls will be investigated over time, both without intervention and before and after shunt surgery.

Conditions

Normal Pressure Hydrocephalus; Hydrocephalus

Keywords

natural history; cerebrospinal fluid; biomarkers; long term follow-up

Outcome Measures

Primary Outcomes (3)

• Frequency of patients with prodromal iNPH that requires shunt surgery within 6 years from inclusion.

  Symptoms are assessed with the idiopathic Normal Pressure Hydrocephalus scale (iNPH-scale) with addition of the gait tests: 10 meter walking in maximum speed, timed up and go test (TUG) and 3 m walking backwards. Each center decides when symptoms have progressed enough to motivate shunt surgery according to local traditions and routine. Low values in time and steps of the gait tests indicate good performance and high values of the iNPH-scale (range: 0-100) indicates good performance.

  From date of inclusion until decision of shunt surgery, assessed up to 72 months

• Frequency of patients with prodromal iNPH that progress to symptomatic iNPH

  Symptoms are assessed with the iNPH-scale with addition of the gait tests: 10 meter walking in maximum speed, timed up and go test (TUG) and 3 m walking backwards. A patient is considered symptomatic when total iNPH-scale is reduced by at least 20 points or the mean speed of the gait tests are reduced by 20%. Low values in time and steps of the gait tests indicate good performance and high values of the iNPH-scale (range: 0-100) indicates good performance.

  From date of inclusion until 20 points reduction in total iNPH-scale score or 20% reduction in gait speed, assessed up to 72 months

• Post operative improvement in iNPH-scale score in patients with mild, moderate and severe preoperative symptoms

  Differences in short (3 and 12 months) and long-term outcome (36 and 60 months) measured as change between preoperative and postoperative iNPH-scale score will be compared between patients with mild, moderate and severe preoperative symptoms. High values of the iNPH-scale (range: 0-100) indicates good performance.

  Change from preoperative (last visit before surgery) iNPH scale at 3 months, 12 months, 36 months and 60 months follow-up.

Secondary Outcomes (9)

• Change in white matter hyperintensities (WMH)

  Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months

• Change in brain morphology

  Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months

• Change in ventricular volume

  Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months

• Change in parenchymal water content

  Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months

• Change in cerebral myelin volume

  Change from baseline at 24 months, at 48 months and at time of decision of shunt surgery, assessed up to 72 months

Study Arms (3)

Group 1 - prodromal iNPH

Individuals with typical imaging findings consistent with iNPH but none or too mild symptoms to motivate shunt surgery.

Procedure: Shunt surgery

Group 2 - Healthy controls

Age matched healthy controls

Group 3 - symptomatic iNPH

Patients with symptomatic iNPH

Procedure: Shunt surgery

Interventions

Shunt surgery PROCEDURE

Shunt surgery according to each local centers routine

Group 1 - prodromal iNPH; Group 3 - symptomatic iNPH

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients in Group 1 can be included from patients referred to a tertiary hydrocephalus center after investigations/work-up have shown too mild symptoms to motivate shunt surgery. Healthy age-matched controls (Group 2) can be included by advertising and by asking relatives to patients in Group 1 and Group 3. For each included individual in Group 1 (prodromal iNPH), two patients are included in Group 3 (symptomatic iNPH). These patients are consecutively included at each center from routine patients that are planned for shunt surgery. They should be age matched with the individual in Group 1 (+/- 3 years).

You may qualify if:

• Brain imaging with both:
• Evans index \> 0.3
• Callosal angle ≤ 90 º or:
• Disproportionately enlarged subarachnoid space hydrocephalus (DESH) - defined as: enlarged ventricles, dilated sylvian fissures and tight sulci at the high convexity.
• Absence of symptoms or too mild symptoms to motivate shunt surgery according to local routine, and all of the following:
• Normal gait pattern, or slight disturbance of the gait pattern that is not considered to be caused by a disease in the central nervous system (CNS).
• Gait velocity (maximum gait speed), men ≥ 1.4 m/s; women ≥ 1.25 m/s.
• Rombergs test with eyes open \> 60 seconds
• Mini Mental State Examination (MMSE) ≥ 27 or Montreal Cognitive Assessment (MoCA) ≥ 23
• Informed consent

You may not qualify if:

• Contraindication for MRI
• Other serious disease with expected survival less than three years
• Other type of hydrocephalus:
• non-communicating hydrocephalus
• secondary communicating hydrocephalus
• suspected congenital hydrocephalus (severely enlarged ventricles, narrow sylvian fissures and normal non-compressed sulci at the high convexity or morphological findings consistent with PaVM18)
• Anticoagulants in a dose that hinders lumbar puncture
• Age \> 65 years
• Previously known relevant neurological disease
• Pathological gait pattern with unknown reason.
• MMSE \< 27 or MoCA \< 26.
• Anticoagulants in a dose that hinders lumbar puncture
• iNPH diagnosis according to international guidelines.19
• Age matched with the individual in Group 1 (+/- 3 years)
• Previous stroke (clinical stroke, not only radiologically verified)

Sponsors & Collaborators

• Johan Virhammar: lead
• Swedish Society for Medical Research: collaborator

Study Sites (7)

Kuopio University Hospital

Kuopio, Finland

NOT YET RECRUITING

Bellaria Hospital

Bologna, Italy

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

NOT YET RECRUITING

Linköping University Hospital

Linköping, Sweden

NOT YET RECRUITING

Karolinska University Hospital

Stockholm, Sweden

NOT YET RECRUITING

Umeå University Hospital

Umeå, Sweden

NOT YET RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid Whole blood Plasma Serum

MeSH Terms

Conditions

Hydrocephalus, Normal Pressure; Hydrocephalus

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Johan Virhammar, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johan Virhammar, MD, PhD

CONTACT

+46186110000; johan.virhammar@neuro.uu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: May 10, 2023
• First Posted: June 20, 2023
• Study Start: November 1, 2023
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

IT (1); SE (5); FI (1)