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Beta-amiloid and Phospho-tau Proteins in CSFNCT05915000

CSF Protein Markers as Prognostic Indicators of the Response to CSF Shunt in Normotensive Hydrocephalus

An observational study of Beta-amiloid and Phospho-tau Proteins in CSF and Ventricular Size After CSF Shunt, run by University of Valencia at 2 sites in Spain.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

In all published series of adult chronic hydrocephalus, there is a percentage between twenty and twenty-five percent of patients who present poor results after implantation of a cerebrospinal fluid shunt,1-11 usually ventriculoperitoneal. The lumboperitoneal shunt is also used but much more rarely. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lumbar CSF protein marker determination
How many people
150 participants
Where
2 sitesSpain
Study dates
13 Jun 2019to Dec 2029
Phase
Observational
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The study sample will be made up only of patients who meet the suspected diagnosis of adult chronic hydrocephalus, who are the ones who are going to have the valve implanted and followed up over time. In addition, the sample will be extracted with the biomarkers. The presence or absence of these biomarkers and their levels will be correlated with the clinical evolution of the patients so that these biomarkers could be used as prognostic indicators or to early identify those subjects in whom the cause of the symptoms was not really hydrocephalus but incipient dementia of another type (or other pathology).

Who may be able to join

  • Minimum age of 18 years, there is no maximum age, especially if it is understood that this pathology is more frequent as one advance in age, especially among males; pathology compatible with chronic adult hydrocephalus

Who cannot join

  • All patients whose suspected diagnosis is not adult chronic hydrocephalus will be excluded, specifically those with cerebrovascular disease, dementia not due to adult chronic hydrocephalus, Alzheimer's disease, Parkinson's disease, and hereditary degenerative brain pathology. Huntington's chorea

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Vicente Vanaclocha, Full Professor contact

+34 963 13 18 00 ext. 438500

vicente.vanaclocha@uv.es

Clinical Research Support Office contact

investigacion.hguv@gva.es

Spain2 sites, 2 recruiting
  • Hospital General Universitario de Valencia

    Valencia, Valencia, 46015

    Vicente Vanaclocha, Professor MD PhD, +34 669 79 00 13, vvanaclo@hotmail.com

    Recruiting
  • Vicente Vanaclocha

    Valencia, Valencia, 46015

    Vicente Vanaclocha Vanaclocha, Prof MD PhD, 34-669790013, vvanaclo@hotmail.com

    Vicente Vanaclocha Vanaclocha, Prof MD PhD, 669790013, vvanaclo@hotmail.com

    Recruiting

Other trials in Spain

About this study

Official title: Alterations of CSF Protein Markers as Prognostic Indicator of the Response to Cerebrospinal Fluid Shunting in Chronic Hydrocephalus in Adults

In all published series of adult chronic hydrocephalus, there is a percentage between twenty and twenty-five percent of patients who present poor results after implantation of a cerebrospinal fluid shunt,1-11 usually ventriculoperitoneal. The lumboperitoneal shunt is also used but much more rarely.

The diagnosis of this pathology is based on the clinical picture, neuroimaging studies (Evans index and corpus callosum angle), cerebrospinal fluid dynamics tests (Katzman test), and invasive intracranial pressure measurements. Despite all this diagnostic arsenal, there is a high percentage of patients (mentioned above) in which treatment by diversion of cerebrospinal fluid does not offer the expected results. Traditionally, this has been attributed to chronic adult hydrocephalus being associated with other types of dementia. This may be the case in some patients, and it would be important to predict which patients will not improve or who will improve poorly in the case of insertion of a cerebrospinal fluid shunt.

Read the detailed description

Adult chronic hydrocephalus, also known as normal pressure hydrocephalus or normal pressure hydrocephalus, presents with the classic Hakim-Adams triad, gait ataxia or "magnetic gait", urinary incontinence, and dementia.

Most cases have an idiopathic origin and constitute the only potentially reversible cause of dementia with surgical treatment (using a system for shunting the cerebrospinal fluid or CSF from the lateral ventricles or the thecal sac to the peritoneal cavity or right atrium ), so it is especially important to diagnose and treat it properly.

The prevalence of this pathology is increasing in line with the increase in the life expectancy of the population.

The diagnosis of this pathology is based on the clinical features, neuroimaging studies (CT and Magnetic Resonance), cerebrospinal fluid dynamics tests (Katzman test), cerebrospinal fluid drainage by lumbar puncture or using lumbar drainage for hours, and invasive measurements of Intracranial Pressure (ICP). Continuous monitoring of Intracranial Pressure with the patient admitted for 3-5 days (continuously night and day) is the most sensitive and specific diagnostic method for this disease, but it also has its false positives and negatives. Likewise, even though complications are very infrequent, it is an invasive technique that requires prolonged and continuous recordings to assess hydrodynamic changes.

Unfortunately, and despite all the diagnostic arsenal, the results of treatment using cerebrospinal fluid shunts (lumboperitoneal or ventriculoperitoneal), even in the best series, yield 20-25% poor results. These poor results have been attributed to many factors, including associated cerebral vascular disease problems, coexisting dementia not always well diagnosed, and Parkinson's disease.

On the other hand, the incorrect indication of a shunt can lead to unnecessary complications, potential morbidity and mortality (subdural hematomas, infections, etc.), and the low success rates mentioned above. Therefore, it is necessary to optimize the diagnosis and treatment of these patients as much as possible.

In an attempt to improve the diagnostic arsenal and, above all, try to predict which patients will improve and in which areas (cognitive, motor, or sphincter control), some researchers have studied the levels of certain proteins or peptides. in the cerebrospinal fluid obtained by a lumbar or ventricular puncture to try to find some kind of correlation between the levels of these protein markers and the type of dementia (Alzheimer's, for example, or adult chronic hydrocephalus) and the response to be expected with the implantation of a cerebrospinal fluid shunt. The markers have been highly varied (amyloid β1-42, amyloid β1-40, T-tau, phospho-tau, neurofilament light chain protein, neurogranin, monocyte chemoattractant protein), and not all of them are available to all hospitals. In our environment, we have the determination in cerebrospinal fluid of the Aβ1-42 amyloid, phospho-tau, and h-tau proteins, which are the most widely used internationally. The purpose of this study is to try to see if there is a correlation between the levels of cerebrospinal fluid obtained by lumbar puncture during the practice of the Katzman test and the results of the implantation of a cerebrospinal fluid shunt and to try to find out which marker is related to which the improvement of each of the three symptoms that afflict patients with adult chronic hydrocephalus, that is, cognitive impairment, gait problems, and inadequate sphincter control.

Being tested
Lumbar CSF protein marker determination
Keywords
Hydrocephalus, Normal pressure hydrocephalus, CSF shunt, Cognitive impairment
Medical subject headings
Cognitive Dysfunction, Hydrocephalus, Hydrocephalus, Normal Pressure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lumbar CSF protein marker determinationDiagnostic test

    The cerebrospinal fluid levels of the Aβ1-42 amyloid, h-tau and phospho-tau proteins will be assessed. The response of patients to the possible implantation of a ventricular peritoneal shunt will be assessed through neuropsychological, gait and ventricular size studies assessed through cerebral magnetic resonance studies.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Correlation Between CSF Amyloid β1-42 Level and Shunt Response

    Correlation between lumbar CSF Amyloid β1-42 concentration and clinical outcome following CSF shunting.

    Unit of Measure: pg/mL

    Measured: 1 year

  2. Correlation Between CSF Total Tau (h-tau) Level and Shunt Response

    Correlation between lumbar CSF total tau concentration and clinical outcome following CSF shunting.

    Unit of Measure: pg/mL

    Measured: 1 year

  3. Correlation Between CSF Phospho-Tau Level and Shunt Response

    Correlation between lumbar CSF phospho-tau concentration and clinical outcome following CSF shunting.

    Unit of Measure: pg/mL

    Measured: 1 year

  4. Threshold Levels of CSF Biomarkers Associated With Poor Shunt Response

    Identification of cutoff values of CSF β1-42 amyloid, total tau, and phospho-tau associated with poor clinical response after CSF shunting.

    Unit of Measure: pg/mL

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2023
  2. Study start13 Jun 2019
  3. Primary completion17 Mar 2029 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

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
Other
Time perspective
Prospective
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05915000
Sponsor's protocol ID
20/2023
Status last verified
Mar 2026
First submitted
13 Jun 2023
Last updated
22 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Publish data once the study is finished

Publications

  • Braun M, Bjurnemark C, Seo W, Freyhult E, Nyholm D, Niemela V, Blennow K, Zetterberg H, Fallmar D, Kultima K, Virhammar J. Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus. Fluids Barriers CNS. 2022 Feb 14;19(1):15. doi: 10.1186/s12987-022-00306-2.

    PubMed 35164790
  • Thavarajasingam SG, El-Khatib M, Vemulapalli KV, Iradukunda HAS, Laleye J, Russo S, Eichhorn C, Eide PK. Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis. Acta Neurochir (Wien). 2022 Jul;164(7):1719-1746. doi: 10.1007/s00701-022-05154-5. Epub 2022 Mar 1.

    PubMed 35230552
  • Said HM, Kaya D, Yavuz I, Dost FS, Altun ZS, Isik AT. A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias. Clin Interv Aging. 2022 Apr 11;17:467-477. doi: 10.2147/CIA.S360736. eCollection 2022.

    PubMed 35431542
  • Pyrgelis ES, Boufidou F, Constantinides VC, Papaioannou M, Papageorgiou SG, Stefanis L, Paraskevas GP, Kapaki E. Cerebrospinal Fluid Biomarkers in iNPH: A Narrative Review. Diagnostics (Basel). 2022 Nov 28;12(12):2976. doi: 10.3390/diagnostics12122976.

    PubMed 36552981
  • Darrow JA, Lewis A, Gulyani S, Khingelova K, Rao A, Wang J, Zhang Y, Luciano M, Yasar S, Moghekar A. CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus. Neurol Clin Pract. 2022 Apr;12(2):91-101. doi: 10.1212/CPJ.0000000000001156.

    PubMed 35733946
  • Lukkarinen H, Tesseur I, Pemberton D, Van Der Ark P, Timmers M, Slemmon R, Janssens L, Streffer J, Van Nueten L, Bottelbergs A, Rauramaa T, Koivisto AM, Herukka SK, Korhonen VE, Junkkari A, Hiltunen M, Engelborghs S, Blennow K, Zetterberg H, Kolb HC, Leinonen V. Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2021;80(4):1629-1642. doi: 10.3233/JAD-201361.

    PubMed 33720890
  • Kawamura K, Miyajima M, Nakajima M, Kanai M, Motoi Y, Nojiri S, Akiba C, Ogino I, Xu H, Kamohara C, Yamada S, Karagiozov K, Ikeuchi T, Kondo A, Arai H. Cerebrospinal Fluid Amyloid-beta Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2021;83(1):179-190. doi: 10.3233/JAD-210226.

    PubMed 34275898
  • Hua R, Liu C, Liu X, Zhu J, Zhang J, Wang L, Shi Z, Li J, Kong S, Yang C, Liu N, Liu L, Sun J, Yang Q, Wu Y, Zhou Y, Li Y, Xing Y. Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus. Front Aging Neurosci. 2021 May 20;13:665878. doi: 10.3389/fnagi.2021.665878. eCollection 2021.

    PubMed 34093167
  • Jingami N, Uemura K, Asada-Utsugi M, Kuzuya A, Yamada S, Ishikawa M, Kawahara T, Iwasaki T, Atsuchi M, Takahashi R, Kinoshita A. Two-Point Dynamic Observation of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2019;72(1):271-277. doi: 10.3233/JAD-190775.

    PubMed 31561378
  • Jeppsson A, Wikkelso C, Blennow K, Zetterberg H, Constantinescu R, Remes AM, Herukka SK, Rauramaa T, Nagga K, Leinonen V, Tullberg M. CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics. J Neurol Neurosurg Psychiatry. 2019 Oct;90(10):1117-1123. doi: 10.1136/jnnp-2019-320826. Epub 2019 Jun 5.

    PubMed 31167811
  • Nakajima M, Miyajima M, Ogino I, Akiba C, Kawamura K, Kamohara C, Fusegi K, Harada Y, Hara T, Sugano H, Tange Y, Karagiozov K, Kasuga K, Ikeuchi T, Tokuda T, Arai H. Preoperative Phosphorylated Tau Concentration in the Cerebrospinal Fluid Can Predict Cognitive Function Three Years after Shunt Surgery in Patients with Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2018;66(1):319-331. doi: 10.3233/JAD-180557.

    PubMed 30248058
  • Akiba C, Nakajima M, Miyajima M, Ogino I, Motoi Y, Kawamura K, Adachi S, Kondo A, Sugano H, Tokuda T, Irie K, Arai H. Change of Amyloid-beta 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus. J Alzheimers Dis. 2018;63(3):989-1002. doi: 10.3233/JAD-180059.

    PubMed 29710721
  • Chen Z, Liu C, Zhang J, Relkin N, Xing Y, Li Y. Cerebrospinal fluid Abeta42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis. Fluids Barriers CNS. 2017 May 10;14(1):13. doi: 10.1186/s12987-017-0062-5.

    PubMed 28486988
  • Craven CL, Baudracco I, Zetterberg H, Lunn MPT, Chapman MD, Lakdawala N, Watkins LD, Toma AK. The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2017 Dec;159(12):2293-2300. doi: 10.1007/s00701-017-3314-x. Epub 2017 Sep 9.

    PubMed 28889317

Questions about this trial

What is this clinical trial studying?

An observational study of Beta-amiloid and Phospho-tau Proteins in CSF and Ventricular Size After CSF Shunt, run by University of Valencia at 2 sites in Spain.

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: looking for participants now, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Spain. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Vicente Vanaclocha, Full Professor (+34 963 13 18 00 ext. 438500, vicente.vanaclocha@uv.es), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Correlation Between CSF Amyloid β1-42 Level and Shunt Response (time frame: 1 year). The study lists 4 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 NCT05915000, which also lists 14 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 22 Apr 2026.

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