Normal Pressure Hydrocephalus Biomarkers Investigation (NORPHY)

September 29, 2022 updated by: Luigi Iuliano, University of Roma La Sapienza

Liquor Oxysterols Concentrations as Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Normal Pressure Hydrocephalus (NPH) is a clinical condition that induces cognitive deterioration that can be reverted, at least in part, by introducing ventricular-peritoneal diversion controlled by a miniaturized valve system.

Mechanisms involved in such an improvement of cognitive function after liquor diversion are unknown.

Oxysterols are a family of cholesterol-related compounds having diverse biological functions. Among others, they are involved in cholesterol homeostasis in the brain and are detectable in liquor, potentially impacting neurodegeneration.

NPH is an ideal clinical model to study oxysterol distribution in liquor before and after ventricular-peritoneal diversion.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Normal-pressure hydrocephalus (NPH) is a progressive, chronic, and extremely complex syndrome, firstly described in 1957, which represents the most common form of reversible dementia in the elderly.

The onset of NPH is on average in the seventh decade of life, with a slightly higher prevalence in males, and the Adam-Hakim triad, which includes dementia, urinary incontinence, and gait deviations, constitutes its clinical mainstay.

Clinical manifestations of NPH are hard to notice, especially at the onset, and the patient itself may not grasp the presence of early signs of NPH until a major event - a fall, for example, occurs.

Diagnosis of NPH is made upon clinical and radiological data and on the effectiveness of cerebrospinal fluid (CSF) shunting by ventricular diversion.

Mechanisms involved in the development of NPH are mainly unknown. Oxysterols are sterol compounds congeners of cholesterol with diverse biological properties. Some of them are linked to cholesterol trafficking in the brain - e.g. 24S-hydroxycholesterol (24S-HC) that allows the transport of cholesterol from the brain to the liver, and are supposedly implicated in neurodegenerative diseases. Evaluation of CSF oxysterols concentration in patients diagnosed with NPH constitutes the primary objective of this study.

CSF levels of oxysterols will be evaluated at two key time points: during the diagnostic work-up, via a spinal tap, and during the surgical treatment of NPH, via ventricular diversion.

In particular, within one month of recruitment, patients are evaluated clinically -including brain MR, cognitive function by MMSE, urinary incontinence, and gait deviation, and are subjected to the spinal tap test to meet the criteria of NPH.

Patients eligible for surgery are then subjected, within one month of diagnosis, to ventricular-peritoneal diversion controlled by a miniaturized valve system. This procedure is known to induce impressive amelioration of symptoms, including cognitive ones.

Oxysterol levels are correlated with the degree of cognitive function, i.e. MMSE score before and after surgery. A second sample of oxysterols is collected at the time of surgery from ventricular drainage to look at any potential difference between regional brain oxysterolome, I.,e. peripheral (spinal and central) nervous system.

Oxysterols are quantitatively measured by isotope dilution gas chromatography mass spectrometry. The first objective is to compare oxysterol levels between two different areas of the circulating liquor, i.e. peripheral (spinal site) and central (ventricular site). In this context, the time frame of the two sample collection is set to two months, i.e. surgery is carried out within one month of the diagnostic spinal tap. The second objective is to assess the correlation between oxysterol levels and minimental status examination score.

This study is designed to cast a light on the pathogenesis of NPH and to evaluate the possible correlation between CSF oxysterols concentration and clinical symptoms severity, with a focus on dementia, assessed via cognitive screening tests such as Mini-Mental State Evaluation (MMSE).

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with a confirmed diagnosis of NPH based on clinical and a diagnostic tap-test

Description

Inclusion Criteria:

  • Patients with a diagnosis of NPH

Exclusion Criteria:

  • Patients with a non-performing ASA score to the intervention

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oxysterol levels in peripheral and central brain liquor
Time Frame: 2 months
Comparison between values of quantitative analysis of oxysterols in liquor collected at time of spinal and central liquor obtained at spinal tap and ventricular drainage
2 months
Correlation between oxysterol levels in the peripheral and central liquor and MMSE score
Time Frame: 2 months
Evaluation of potential correlation between oxysterol levels and mini-mental status examination score.
2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Collaborators

AUSL Latina

Investigators

  • Principal Investigator: Gianpaolo Petrella, M.D., AUSL Latina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

October 30, 2022

Primary Completion (ANTICIPATED)

April 1, 2024

Study Completion (ANTICIPATED)

July 1, 2024

Study Registration Dates

First Submitted

June 21, 2022

First Submitted That Met QC Criteria

September 29, 2022

First Posted (ACTUAL)

October 3, 2022

Study Record Updates

Last Update Posted (ACTUAL)

October 3, 2022

Last Update Submitted That Met QC Criteria

September 29, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hydro2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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