White Matter Distortion and Dementia Biomarkers in Normal Pressure Hydrocephalus (NPH)

NCT07103681 | Recruiting DMC

• 2 other identifiers: 311620W0300981
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a progressive condition of the elderly that results in severe disability. iNPH can dramatically respond to Cerebral spinal fluid(CSF)-shunting where excess ventricular fluid is diverted from the brain. Not all patients with iNPH respond to CSF-shunting however. The reasons for this are uncertain. Aim 1: To understand if specific nerve pathways (white matter tracts) that are near ventricles are damaged in patients that respond to shunting as opposed to those that do not. Aim 2: Can we explain shunt non-responsiveness by screening for dementia like illnesses (neurodegeneration) using a large array of methods. Aim 3: To understand whether wearable activity and bed sleep monitors are palatable in a NPH population and to understand if these metrics relate to quality of life. Aim 4: To see whether self-administered digital cognitive assessments can measure improvements pre and post surgery.

Conditions

Normal Pressure Hydrocephalus

Keywords

hydrocephalus; activity monitors; gait impairment; shunt surgery; protokinetic; normal pressure hydrocephalus; shunt-responsiveness; white matter tractography; diffusion tensor imaging; neurodegenerative; NPH

Outcome Measures

Primary Outcomes (1)

• White Matter Pathway Diffusion Metrics

  Change from baseline in diffusion tensor imaging (DTI) metrics of white matter pathways (e.g. FA, AD, RD) before and after shunt surgery. The following tracts will be studied: corpus collosum, internal capsule, corona radiata and anterior thalamic radiation.

  Perioperative

Secondary Outcomes (20)

• Neurodegenerative Biomarkers and CSF-shunt responsiveness

  Perioperative

• Serum Neurodegenerative Biomarkers

  From enrolment, at periprocedural and up to 27 weeks

• Sleep Monitoring

  From enrolment and through study completion, an average of 1 year

• Activity Monitoring

  From enrolment and through study completion, an average of 1 year

• Tinetti Performance Oriented Mobility Assessment Score (balance)

  From enrolment, at periprocedural and up to 27 weeks

Study Arms (2)

Group 1

Group 1 includes adults over 60 years old diagnosed with late-onset communicating hydrocephalus, characterised by gait apraxia, with or without cognitive impairment and urinary dysfunction. Eligibility is confirmed through clinical imaging showing an Evan's index \>0.3 and an iNPH Radscale score \>4. Individuals with recent severe head trauma, high-pressure hydrocephalus, or alternative causes for similar symptoms are excluded. This criteria for group 1 ensures a distinct group for studying the late-onset, communicating form of the condition.

Procedure: Ventriculoperitoneal Shunt (VP); Procedure: Brain and Skin Biopsy; Diagnostic Test: MRI Brain

Group 2

Group 2 will include 30 adult patients with asymptomatic chronic hydrocephalus, non-hydrocephalus dementia and healthy controls.

Interventions

Ventriculoperitoneal Shunt (VP) PROCEDURE

VP Shunt surgery involves surgical insertion of a catheter (tube) to divert brain fluid from the cerebral ventricles to the abdominal peritoneum. This will be performed in Group 1 patients as clinically indicated.

Also known as: VP Shunt

Group 1

Brain and Skin Biopsy PROCEDURE

Brain and skin biopsy's may be taken during the VP shunt to assist in histological analysis for neurodegenerative changes.

Group 1

MRI Brain DIAGNOSTIC_TEST

MRI brain with diffusion imagining will be performed before and after shunt surgery.

Group 1

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with hydrocephalus, neurodegenerative disease and healthy controls will be recruited by Dr Chris Carswell at Imperial College Hospital NHS Trust.

You may qualify if:

• Adult patients \>60
• With gait apraxia
• With or without cognitive impairment
• Urinary dysfunction
• Communicating Hydrocephalus

You may not qualify if:

• Asymptomatic hydrocephalus
• High pressure-hydrocephalus
• Serious head injury within 5 years of presentation or a clear secondary cause (e.g. brain infection)
• History of childhood gait disturbance
• Clear alternative explanation for symptoms (e.g. Parkinson's disease with limb rigidity, peripheral neuropathy with sensory ataxia, cervical myelopathy).
• Too frail for shunt surgery
• Medically unstable (e.g. active angina, respiratory disease, recurrent delirium, active epilepsy).
• Unable to tolerate MRI brain imaging
• Unable to have a lumbar puncture
• Immobile
• Unable to attend the hospital for study visits
• Group 2 (asymptomatic and non-hydrocepahlus dementia and healthy controls):
• Healthy Carers
• Members of the Public
• Staff of Imperial College/ICHT

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• University College, London: collaborator
• University of Edinburgh: collaborator
• King's College London: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood, CSF, brain and skin will be retained for 10 years following the study end and keeping with the ICL policies. Unless used in other ongoing studies.

MeSH Terms

Conditions

Hydrocephalus, Normal Pressure; Hydrocephalus

Interventions

Ventriculoperitoneal Shunt

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cerebrospinal Fluid Shunts; Anastomosis, Surgical; Surgical Procedures, Operative; Neurosurgical Procedures

Central Study Contacts

Chris Carswell

CONTACT

+44 20311 1234; NPH@imperial.ac.uk

Harvey G Burns

CONTACT

+44 20311 1234; NPH@imperial.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: August 5, 2025
• Study Start: March 25, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

GB (1)