Normal Pressure Hydrocephalus Biomarkers Investigation

NCT ID: NCT05562596

Last Updated: 2022-10-03

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

UNKNOWN

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-10-30

Study Completion Date

2024-07-01

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Normal Pressure Hydrocephalus Cognitive Impairment

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Interventions

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Measurement of oxysterol profile, including 20 molecules, in liquor before and after surgery

Samples are quantitated by deuterium-labeled mass-spectrometry amalysis.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients with a diagnosis of NPH

Exclusion Criteria

* Patients with a non-performing ASA score to the intervention
Minimum Eligible Age

60 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AUSL Latina

UNKNOWN

Sponsor Role collaborator

University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Luigi Iuliano

Professor of Internal Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Luigi Iuliano, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

Gianpaolo Petrella, M.D.

Role: PRINCIPAL_INVESTIGATOR

AUSL Latina

Locations

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Goretti Hospital

Latina, LT, Italy

Site Status

Countries

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Italy

Central Contacts

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Luigi Iuliano, M.D.

Role: CONTACT

+393406462332

Gianpaolo Petrella, M.D.

Role: CONTACT

+393476352149

Facility Contacts

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Gianpaolo Petrella, M.D.

Role: primary

+393476352149

References

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Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci. 1965 Jul-Aug;2(4):307-27. doi: 10.1016/0022-510x(65)90016-x. No abstract available.

Reference Type BACKGROUND
PMID: 5889177 (View on PubMed)

Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. SYMPTOMATIC OCCULT HYDROCEPHALUS WITH "NORMAL" CEREBROSPINAL-FLUID PRESSURE. A TREATABLE SYNDROME. N Engl J Med. 1965 Jul 15;273:117-26. doi: 10.1056/NEJM196507152730301. No abstract available.

Reference Type BACKGROUND
PMID: 14303656 (View on PubMed)

Williams MA, Relkin NR. Diagnosis and management of idiopathic normal-pressure hydrocephalus. Neurol Clin Pract. 2013 Oct;3(5):375-385. doi: 10.1212/CPJ.0b013e3182a78f6b.

Reference Type BACKGROUND
PMID: 24175154 (View on PubMed)

Hashimoto M, Ishikawa M, Mori E, Kuwana N; Study of INPH on neurological improvement (SINPHONI). Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study. Cerebrospinal Fluid Res. 2010 Oct 31;7:18. doi: 10.1186/1743-8454-7-18.

Reference Type BACKGROUND
PMID: 21040519 (View on PubMed)

Mori E, Ishikawa M, Kato T, Kazui H, Miyake H, Miyajima M, Nakajima M, Hashimoto M, Kuriyama N, Tokuda T, Ishii K, Kaijima M, Hirata Y, Saito M, Arai H; Japanese Society of Normal Pressure Hydrocephalus. Guidelines for management of idiopathic normal pressure hydrocephalus: second edition. Neurol Med Chir (Tokyo). 2012;52(11):775-809. doi: 10.2176/nmc.52.775.

Reference Type BACKGROUND
PMID: 23183074 (View on PubMed)

Forner Giner J, Sanz-Requena R, Florez N, Alberich-Bayarri A, Garcia-Marti G, Ponz A, Marti-Bonmati L. Quantitative phase-contrast MRI study of cerebrospinal fluid flow: a method for identifying patients with normal-pressure hydrocephalus. Neurologia. 2014 Mar;29(2):68-75. doi: 10.1016/j.nrl.2013.02.016. Epub 2013 May 3. English, Spanish.

Reference Type BACKGROUND
PMID: 23643684 (View on PubMed)

Iuliano L, Crick PJ, Zerbinati C, Tritapepe L, Abdel-Khalik J, Poirot M, Wang Y, Griffiths WJ. Cholesterol metabolites exported from human brain. Steroids. 2015 Jul;99(Pt B):189-93. doi: 10.1016/j.steroids.2015.01.026. Epub 2015 Feb 7.

Reference Type BACKGROUND
PMID: 25668615 (View on PubMed)

Crick PJ, William Bentley T, Abdel-Khalik J, Matthews I, Clayton PT, Morris AA, Bigger BW, Zerbinati C, Tritapepe L, Iuliano L, Wang Y, Griffiths WJ. Quantitative charge-tags for sterol and oxysterol analysis. Clin Chem. 2015 Feb;61(2):400-11. doi: 10.1373/clinchem.2014.231332. Epub 2014 Dec 15.

Reference Type BACKGROUND
PMID: 25512642 (View on PubMed)

Testa G, Staurenghi E, Zerbinati C, Gargiulo S, Iuliano L, Giaccone G, Fanto F, Poli G, Leonarduzzi G, Gamba P. Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation. Redox Biol. 2016 Dec;10:24-33. doi: 10.1016/j.redox.2016.09.001. Epub 2016 Sep 16.

Reference Type BACKGROUND
PMID: 27687218 (View on PubMed)

Other Identifiers

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Hydro2022

Identifier Type: -

Identifier Source: org_study_id

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