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

NCT ID: NCT07103681

Last Updated: 2025-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-03-25

Study Completion Date

2028-02-29

Brief Summary

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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.

Detailed Description

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This single-centre observational cohort study will follow 50 patients diagnosed with symptomatic Normal Pressure Hydrocephalus (NPH) (idiopathic or late presenting congenital hydrocephalus and not secondary hydrocephalus) through their clinical journey, from initial assessment to post-CSF shunt surgery or a time when surgery is decided against. Separate groups of 50 asymptomatic individuals with chronic hydrocephalus and non-hydrocephalus individuals will act as controls.

Participants will undergo comprehensive clinical assessments including gait, cognitive and urinary evaluations, quality of life measures, serum and CSF degenerative biomarker analysis, diffusion-weighted Magnetic Resonance Imaging (MRI) and optional brain and skin biopsies. Data collection will focus on capturing changes in clinical presentation and imaging findings before and after shunting. REDCap will be utilised as the primary tool for data storage.

Primary outcome measures assess pre and post-shunting imaging changes in shunt-responders and non-responders. Shunt response will be defined as 10% improvement in gait speed. Secondary outcomes evaluate the relationship between biomarkers and clinical outcomes. Longitudinal data will help identify factors distinguishing responders from non-responders, with descriptive and inferential statistics used.

Conditions

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Normal Pressure Hydrocephalus

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Ventriculoperitoneal Shunt (VP)

Intervention Type 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.

Brain and Skin Biopsy

Intervention Type PROCEDURE

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

MRI Brain

Intervention Type DIAGNOSTIC_TEST

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

Group 2

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

No interventions assigned to this group

Interventions

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Ventriculoperitoneal Shunt (VP)

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.

Intervention Type PROCEDURE

Brain and Skin Biopsy

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

Intervention Type PROCEDURE

MRI Brain

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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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VP Shunt

Eligibility Criteria

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Inclusion Criteria

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


* Healthy Carers
* Members of the Public
* Staff of Imperial College/ICHT
* Non-NPH Dementias (including Alzheimer's disease or vascular dementia)
* Asymptomatic Hydrocephalus

Exclusion Criteria

* 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):


\- Unable to attend the hospital for study visits
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Medical Research Council

OTHER_GOV

Sponsor Role collaborator

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

University of Edinburgh

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Chris Carswell

Role: CONTACT

+44 20311 1234

Harvey G Burns

Role: CONTACT

+44 20311 1234

Facility Contacts

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Chris Carswell, PHD, FRCP

Role: primary

+44 20311 1234

Harvey G Burns

Role: backup

+44 20311 1234

Other Identifiers

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W0300981

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

311620

Identifier Type: -

Identifier Source: org_study_id

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