Normal Pressure HydrocephalusNORPHYNCT05562596
Normal Pressure Hydrocephalus Biomarkers Investigation
An observational study of Normal Pressure Hydrocephalus and Cognitive Impairment, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Normal Pressure Hydrocephalus, Cognitive Impairment
- What is being tested?
- Measurement of oxysterol profile, including 20 molecules, in liquor before and after surgery
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 30 Oct 2022to 1 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a confirmed diagnosis of NPH based on clinical and a diagnostic tap-test
Who may be able to join
- Patients with a diagnosis of NPH
Who cannot join
- Patients with a non-performing ASA score to the intervention
Trial locations and contacts
1 site in 1 country.
Italy1 site
Goretti Hospital
Latina, LT, 04100
Gianpaolo Petrella, M.D., +393476352149, g.petrella@ausl.latina.it
About this study
Official title: 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.
Read the 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).
- Being tested
- Measurement of oxysterol profile, including 20 molecules, in liquor before and after surgery
- Keywords
- normal pressure hydrocephalus, neurodegeneration, cognitive impairment, oxysterols, mass spectrometry
- Medical subject headings
- Hydrocephalus, Normal Pressure, Cognitive Dysfunction, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measurement of oxysterol profile, including 20 molecules, in liquor before and after surgeryDiagnostic test
Samples are quantitated by deuterium-labeled mass-spectrometry amalysis.
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxysterol levels in peripheral and central brain liquor
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
Measured: 2 months
Correlation between oxysterol levels in the peripheral and central liquor and MMSE score
Evaluation of potential correlation between oxysterol levels and mini-mental status examination score.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study start30 Oct 2022 (estimated)
- Primary completion1 Apr 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Normal Pressure HydrocephalusStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Collaborators
- AUSL Latina
- Responsible party
- Principal investigator, Luigi Iuliano, University of Roma La Sapienza
- Investigators
- Luigi Iuliano, M.D., Principal investigator, University of Roma La SapienzaGianpaolo Petrella, M.D., Principal investigator, AUSL Latina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05562596
- Sponsor's protocol ID
- Hydro2022
- Acronym
- NORPHY
- Status last verified
- Sep 2022
- First submitted
- 21 Jun 2022
- Last updated
- 3 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 5889177Adams 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.
PubMed 14303656Williams 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.
PubMed 24175154Hashimoto 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.
PubMed 21040519Mori 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.
PubMed 23183074Forner 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.
PubMed 23643684Iuliano 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.
PubMed 25668615Crick 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.
PubMed 25512642Testa 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.
PubMed 27687218
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liquor Oxysterols Concentrations as Biomarkers in Idiopathic Normal Pressure Hydrocephalus
- ClinicalTrials.gov ID
- NCT05562596
- Acronym / sponsor ID
- NORPHY / Hydro2022
- Keywords
- normal pressure hydrocephalus, neurodegeneration, cognitive impairment, oxysterols, mass spectrometry
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Collaborators
- AUSL Latina
- Study start
- 30 Oct 2022 (estimated)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 3 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a confirmed diagnosis of NPH based on clinical and a diagnostic tap-test
Key inclusion criteria (1 listed)
- Patients with a diagnosis of NPH
Key exclusion criteria (1 listed)
- Patients with a non-performing ASA score to the intervention
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measurement of oxysterol profile, including 20 molecules, in liquor before and after surgerySamples are quantitated by deuterium-labeled mass-spectrometry amalysis. | Diagnostic test | – |
Primary outcome
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
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2022.
- Background: PubMed 5889177Hakim 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.
- Background: PubMed 14303656Adams 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.
- Background: PubMed 24175154Williams 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.
- Background: PubMed 21040519Hashimoto 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.
- Background: PubMed 23183074Mori 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.
- Background: PubMed 23643684Forner 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.
- Background: PubMed 25668615Iuliano 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.
- Background: PubMed 25512642Crick 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.
- Background: PubMed 27687218Testa 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luigi Iuliano, M.D. principal investigator
University of Roma La Sapienza
Gianpaolo Petrella, M.D. principal investigator
AUSL Latina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normal Pressure Hydrocephalus and Cognitive Impairment, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luigi Iuliano, M.D. (+393406462332, luigi.iuliano@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxysterol levels in peripheral and central brain liquor (time frame: 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05562596, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2022.