Investigating early signs of Normal Pressure Hydrocephalus

European Study of Prodromal iNPH

Observational Uppsala University Hospital · NCT05910944

This study is trying to see if special brain scans and tests on spinal fluid and blood can help predict how Normal Pressure Hydrocephalus develops in people who have early signs, those with symptoms, and healthy individuals over five years.

Quick facts

Study typeObservational
Enrollment140 (estimated)
SexAll
SponsorUppsala University Hospital Academic / other
Locations7 sites (Kuopio and 6 other locations)
Trial IDNCT05910944 on ClinicalTrials.gov

What this trial studies

This observational study aims to predict the progression from prodromal to symptomatic Normal Pressure Hydrocephalus (NPH) using advanced neuroimaging and biomarkers in cerebrospinal fluid and plasma. It will involve three cohorts: patients with prodromal NPH, symptomatic NPH patients, and healthy controls, followed over five years across seven European centers. Participants will undergo MRI scans, lumbar punctures for CSF and blood samples, and regular assessments to monitor changes in symptoms and biomarkers. The study will also evaluate the effects of shunt surgery on these variables.

Who should consider this trial

Good fit: Ideal candidates include individuals with imaging features of prodromal NPH but without significant symptoms requiring shunt surgery.

Not a fit: Patients with contraindications for MRI or other serious diseases with limited life expectancy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier diagnosis and intervention for patients at risk of developing symptomatic NPH.

How similar studies have performed: While this approach is novel in its specific focus on prodromal NPH, similar studies investigating biomarkers and neuroimaging in other conditions have shown promise.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion criteria - Group 1 - prodromal iNPH

* 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

Exclusion criteria - Group 1 - prodromal iNPH

* 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

Inclusion criteria - Group 2 - healthy controls

• Age \> 65 years

Exclusion criteria - Group 2 - healthy controls:

* Imaging findings meet inclusion criteria of Group 1
* Previously known relevant neurological disease
* Pathological gait pattern with unknown reason.
* MMSE \< 27 or MoCA \< 26.
* Anticoagulants in a dose that hinders lumbar puncture

Inclusion criteria Group 3 symptomatic iNPH

* iNPH diagnosis according to international guidelines.19
* Age matched with the individual in Group 1 (+/- 3 years)

Exclusion criteria Group 3 symptomatic iNPH

* Previous stroke (clinical stroke, not only radiologically verified)
* Other serious disease with expected survival less than three years

Where this trial is running

Kuopio and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Normal Pressure HydrocephalusHydrocephalusnatural historycerebrospinal fluidbiomarkerslong term follow-up
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.