HydrocephalusGLINFANPH_2021NCT06857136

The Role of the Glymphatic System Avaluated Thourgh mr Imaging in the Diagnosis and Management of NPH

An observational study of Hydrocephalus and Normal Pressure Hydrocephalus, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The goal of this observational study is to evaluate the role of DTI-ALPS in the diagnostic and therapeutic management of NPH The main questions it aims to answer are: Whether the glymphatic system (GS) is actually impaired in NPH Whether DTI-ALPS index can predict the positive response to tap test (TT) and to… Read more about this study

Who is it for?: Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for: Hydrocephalus, Normal Pressure Hydrocephalus
Type of treatment: Injection or infusion
How many people: 29 participants
Where: 1 siteItaly
Study dates: 15 Jun 2021to 31 Dec 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 50 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Study population: Patients affected by normal pressure hydrocephalus

Who may be able to join

clinical and radiological diagnosis of probable NPH according to existing guidelines
age of over 50 years

Who cannot join

inability to undergo MR
diagnosis of any other neurological pathology, particularly neurodegenerative or neuroinflammatory
previous neurosurgical interventions on the brain of any type.
inability to undergo general anaesthesia

Trial locations and contacts

1 site in 1 country.

Italy1 site

Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133

Other trials in Italy

About this study

The goal of this observational study is to evaluate the role of DTI-ALPS in the diagnostic and therapeutic management of NPH

The main questions it aims to answer are:

Whether the glymphatic system (GS) is actually impaired in NPH
Whether DTI-ALPS index can predict the positive response to tap test (TT) and to ventriculo-peritoneal shunt (VPS) surgery.

A healthy control group of patients (HC group) matched for age with the study group, will undergo MR with DTI-ALPS study

Read the detailed description

Enrolled patients followed a diagnostic-therapeutic pathway, consisting of the following steps:

t0: MR with DTI-ALPS study;
t1 (within 7 days from T0): clinical and neurosurgical assessment with NPH-specific rating scales (detailed below) before and after a lumbar TT, including measurements of opening pressure, drainage of 40-50 mL of CSF and collection of samples for neurodegenerative biomarkers (β-Amyloid 40, 42 total and P-Tau) quantification. An MR with DTI-ALPS study within 6 hours from TT;
t2 (within 3 months from T1): patients with a positive TT response (included responders, IR group) underwent VPS surgery, with CSF samples collected for the same neurodegenerative biomarkers (β-Amyloid 40, 42 total and P-Tau);
t3 (three months after surgery, IR group only): clinical and neurosurgical evaluation using NPH-specific rating scales to classify patients as improved, unchanged, or worsened compared to their preoperative condition; MR with DTI-ALPS study.

Conditions: Hydrocephalus, Normal Pressure Hydrocephalus
Keywords: hydrocephalus, Normal pressure hydrocephalus, NPH, Glymphatic System, DTI-ALPS, Diffusion Tensor Imaging, ALPS-index
Medical subject headings: Hydrocephalus, Hydrocephalus, Normal Pressure

What participants receive

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

Study groups in NCT06857136
Study group	Role	What they receive
Study group		Patients attending the NPH outpatient clinic were prospectively enrolled in the study. The inclusion criteria were: (i) clinical and radiological diagnosis of probable NPH according to existing guidelines and (ii) age of over 50 years. Exclusion criteria were: (i) inability to undergo MR; (ii) a diagnosis of any other neurological pathology, particularly neurodegenerative or neuroinflammatory; (iii) previous neurosurgical interventions on the brain of any type; (iv) inability to undergo general anaesthesia.
Control group		A healthy control group of patients (HC group) matched for age with the IR group, underwent MR with DTI-ALPS study. Exclusion criteria for this group were: (i) a previous diagnosis of any neurological disorder of any type. (ii) a history of neurosurgical intervention of any kind; and (iii) a prior diagnosis of malignancy of any type.

What is being measured

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

Comparison between study and control group
Difference in DTI ALPS index between NPH patients and healthy controls
Measured: 4 years

Secondary outcomes (3)

Difference in response to tap test between NPH patients who responded and those who did not
Difference in DTI ALPS index between NPH who responded to tap test (and underwent to ventircolopetoneal shunt) and those who did not
Measured: 4 years
Change in DTI ALPS index across treatment in NPH patients
Difference in DTI ALPS index in NPH patients between T0 (before TT), T1 (after TT) and T3 (after VP shunt)
Measured: 4 years
Change in CSF degenerative biomarker concentrations
CSF degenerative biomarkers (total tau protein, p-181 tau protein, Aβ42 e Aβ40 protein) variation between T1, T2 and T3
Measured: 4 years

Timeline

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

15 Jun 202131 Dec 2024

First posted4 Mar 2025
Study start15 Jun 2021
Primary completion31 Aug 2024
Study completion31 Dec 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (267)Papers the sponsor has linked to this study.
Other trials for HydrocephalusStudies of the same condition, open and under way.
More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe 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-control
Time perspective: Prospective
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06857136
Sponsor's protocol ID: GLINFANPH_2021
Acronym: GLINFANPH_2021
Status last verified: Feb 2025
First submitted: 26 Feb 2025
Last updated: 11 Feb 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Abu-Rumeileh S, Giannini G, Polischi B, Albini-Riccioli L, Milletti D, Oppi F, Stanzani-Maserati M, Capellari S, Mantovani P, Palandri G, Cortelli P, Cevoli S, Parchi P. Revisiting the Cerebrospinal Fluid Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus: The Bologna Pro-Hydro Study. J Alzheimers Dis. 2019;68(2):723-733. doi: 10.3233/JAD-181012.
PubMed 30883350
Graff-Radford NR. Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus. Neurology. 2014 Oct 21;83(17):1573-5. doi: 10.1212/WNL.0000000000000916.
PubMed 25332445
Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005 Jun;26(2):108-16. doi: 10.1007/s10072-005-0443-4.
PubMed 15995827
Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
PubMed 1202204
Tinetti ME, Williams TF, Mayewski R. Fall risk index for elderly patients based on number of chronic disabilities. Am J Med. 1986 Mar;80(3):429-34. doi: 10.1016/0002-9343(86)90717-5.
PubMed 3953620
Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.
PubMed 1991946
Tian Y, Cai X, Zhou Y, Jin A, Wang S, Yang Y, Mei L, Jing J, Li S, Meng X, Wei T, Liu T, Wang Y, Pan Y, Wang Y. Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study. Stroke Vasc Neurol. 2023 Oct;8(5):413-423. doi: 10.1136/svn-2022-002191. Epub 2023 Apr 12.
PubMed 37045543
Shanks J, Markenroth Bloch K, Laurell K, Cesarini KG, Fahlstrom M, Larsson EM, Virhammar J. Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery. AJNR Am J Neuroradiol. 2019 Mar;40(3):453-459. doi: 10.3174/ajnr.A5972. Epub 2019 Feb 21.
PubMed 30792248
Morone PJ, Dewan MC, Zuckerman SL, Tubbs RS, Singer RJ. Craniometrics and Ventricular Access: A Review of Kocher's, Kaufman's, Paine's, Menovksy's, Tubbs', Keen's, Frazier's, Dandy's, and Sanchez's Points. Oper Neurosurg. 2020 May 1;18(5):461-469. doi: 10.1093/ons/opz194.
PubMed 31420653
Walchenbach R, Geiger E, Thomeer RT, Vanneste JA. The value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry. 2002 Apr;72(4):503-6. doi: 10.1136/jnnp.72.4.503.
PubMed 11909911
Razay G, Vreugdenhil A, Liddell J. A prospective study of ventriculo-peritoneal shunting for idiopathic normal pressure hydrocephalus. J Clin Neurosci. 2009 Sep;16(9):1180-3. doi: 10.1016/j.jocn.2008.12.007. Epub 2009 Jun 3.
PubMed 19497748
Toma AK, Stapleton S, Papadopoulos MC, Kitchen ND, Watkins LD. Natural history of idiopathic normal-pressure hydrocephalus. Neurosurg Rev. 2011 Oct;34(4):433-9. doi: 10.1007/s10143-011-0316-7. Epub 2011 May 19.
PubMed 21594683
Andren K, Wikkelso C, Tisell M, Hellstrom P. Natural course of idiopathic normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry. 2014 Jul;85(7):806-10. doi: 10.1136/jnnp-2013-306117. Epub 2013 Nov 29.
PubMed 24292998
Iseki C, Kawanami T, Nagasawa H, Wada M, Koyama S, Kikuchi K, Arawaka S, Kurita K, Daimon M, Mori E, Kato T. Asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on MRI (AVIM) in the elderly: a prospective study in a Japanese population. J Neurol Sci. 2009 Feb 15;277(1-2):54-7. doi: 10.1016/j.jns.2008.10.004. Epub 2008 Nov 5.
PubMed 18990411
Iseki C, Takahashi Y, Wada M, Kawanami T, Adachi M, Kato T. Incidence of idiopathic normal pressure hydrocephalus (iNPH): a 10-year follow-up study of a rural community in Japan. J Neurol Sci. 2014 Apr 15;339(1-2):108-12. doi: 10.1016/j.jns.2014.01.033. Epub 2014 Feb 3.
PubMed 24656600

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hydrocephalus trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Role of the Glymphatic System Avaluated Thourgh mr Imaging in the Diagnosis and Management of NPH
ClinicalTrials.gov ID: NCT06857136
Acronym / sponsor ID: GLINFANPH_2021 / GLINFANPH_2021
Conditions: Hydrocephalus, Normal Pressure Hydrocephalus
Keywords: hydrocephalus, Normal pressure hydrocephalus, NPH, Glymphatic System, DTI-ALPS, Diffusion Tensor Imaging, ALPS-index
Study type: Observational
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
Study start: 15 Jun 2021 (actual)
Primary completion: 31 Aug 2024 (actual)
Study completion: 31 Dec 2024 (actual)
First posted: 4 Mar 2025 (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.

The goal of this observational study is to evaluate the role of DTI-ALPS in the diagnostic and therapeutic management of NPH

The main questions it aims to answer are:

Whether the glymphatic system (GS) is actually impaired in NPH
Whether DTI-ALPS index can predict the positive response to tap test (TT) and to ventriculo-peritoneal shunt (VPS) surgery.

A healthy control group of patients (HC group) matched for age with the study group, will undergo MR with DTI-ALPS study

Detailed description

Enrolled patients followed a diagnostic-therapeutic pathway, consisting of the following steps:

t0: MR with DTI-ALPS study;
t1 (within 7 days from T0): clinical and neurosurgical assessment with NPH-specific rating scales (detailed below) before and after a lumbar TT, including measurements of opening pressure, drainage of 40-50 mL of CSF and collection of samples for neurodegenerative biomarkers (β-Amyloid 40, 42 total and P-Tau) quantification. An MR with DTI-ALPS study within 6 hours from TT;
t2 (within 3 months from T1): patients with a positive TT response (included responders, IR group) underwent VPS surgery, with CSF samples collected for the same neurodegenerative biomarkers (β-Amyloid 40, 42 total and P-Tau);
t3 (three months after surgery, IR group only): clinical and neurosurgical evaluation using NPH-specific rating scales to classify patients as improved, unchanged, or worsened compared to their preoperative condition; MR with DTI-ALPS study.

Study design

Observational model: Case-control
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Study group	–	–Patients attending the NPH outpatient clinic were prospectively enrolled in the study. The inclusion criteria were: (i) clinical and radiological diagnosis of probable NPH according to existing guidelines and (ii) age of over 50 years. Exclusion criteria were: (i) inability to undergo MR; (ii) a diagnosis of any other neurological pathology, particularly neurodegenerative or neuroinflammatory; (iii) previous neurosurgical interventions on the brain of any type; (iv) inability to undergo general anaesthesia.
Control group	–	–A healthy control group of patients (HC group) matched for age with the IR group, underwent MR with DTI-ALPS study. Exclusion criteria for this group were: (i) a previous diagnosis of any neurological disorder of any type. (ii) a history of neurosurgical intervention of any kind; and (iii) a prior diagnosis of malignancy of any type.

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult
Study population: Patients affected by normal pressure hydrocephalus

Key inclusion criteria (2 listed)

clinical and radiological diagnosis of probable NPH according to existing guidelines
age of over 50 years

Key exclusion criteria (4 listed)

inability to undergo MR
diagnosis of any other neurological pathology, particularly neurodegenerative or neuroinflammatory
previous neurosurgical interventions on the brain of any type.
inability to undergo general anaesthesia

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Comparison between study and control group
Time frame: 4 years
Difference in DTI ALPS index between NPH patients and healthy controls

3 secondary outcomes

Difference in response to tap test between NPH patients who responded and those who did not
Time frame: 4 years
Change in DTI ALPS index across treatment in NPH patients
Time frame: 4 years
Change in CSF degenerative biomarker concentrations
Time frame: 4 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2026.
Background: PubMed 30883350Abu-Rumeileh S, Giannini G, Polischi B, Albini-Riccioli L, Milletti D, Oppi F, Stanzani-Maserati M, Capellari S, Mantovani P, Palandri G, Cortelli P, Cevoli S, Parchi P. Revisiting the Cerebrospinal Fluid Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus: The Bologna Pro-Hydro Study. J Alzheimers Dis. 2019;68(2):723-733. doi: 10.3233/JAD-181012.
Background: PubMed 25332445Graff-Radford NR. Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus. Neurology. 2014 Oct 21;83(17):1573-5. doi: 10.1212/WNL.0000000000000916.
Background: PubMed 15995827Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005 Jun;26(2):108-16. doi: 10.1007/s10072-005-0443-4.
Background: PubMed 1202204Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
Background: PubMed 3953620Tinetti ME, Williams TF, Mayewski R. Fall risk index for elderly patients based on number of chronic disabilities. Am J Med. 1986 Mar;80(3):429-34. doi: 10.1016/0002-9343(86)90717-5.
Background: PubMed 1991946Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.
Background: PubMed 37045543Tian Y, Cai X, Zhou Y, Jin A, Wang S, Yang Y, Mei L, Jing J, Li S, Meng X, Wei T, Liu T, Wang Y, Pan Y, Wang Y. Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study. Stroke Vasc Neurol. 2023 Oct;8(5):413-423. doi: 10.1136/svn-2022-002191. Epub 2023 Apr 12.
Background: PubMed 30792248Shanks J, Markenroth Bloch K, Laurell K, Cesarini KG, Fahlstrom M, Larsson EM, Virhammar J. Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery. AJNR Am J Neuroradiol. 2019 Mar;40(3):453-459. doi: 10.3174/ajnr.A5972. Epub 2019 Feb 21.
Background: PubMed 31420653Morone PJ, Dewan MC, Zuckerman SL, Tubbs RS, Singer RJ. Craniometrics and Ventricular Access: A Review of Kocher's, Kaufman's, Paine's, Menovksy's, Tubbs', Keen's, Frazier's, Dandy's, and Sanchez's Points. Oper Neurosurg. 2020 May 1;18(5):461-469. doi: 10.1093/ons/opz194.
Background: PubMed 11909911Walchenbach R, Geiger E, Thomeer RT, Vanneste JA. The value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry. 2002 Apr;72(4):503-6. doi: 10.1136/jnnp.72.4.503.
Background: PubMed 19497748Razay G, Vreugdenhil A, Liddell J. A prospective study of ventriculo-peritoneal shunting for idiopathic normal pressure hydrocephalus. J Clin Neurosci. 2009 Sep;16(9):1180-3. doi: 10.1016/j.jocn.2008.12.007. Epub 2009 Jun 3.
Background: PubMed 21594683Toma AK, Stapleton S, Papadopoulos MC, Kitchen ND, Watkins LD. Natural history of idiopathic normal-pressure hydrocephalus. Neurosurg Rev. 2011 Oct;34(4):433-9. doi: 10.1007/s10143-011-0316-7. Epub 2011 May 19.
Individual participant dataSharing planned: No

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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.

Morgan A Broggi, MD principal investigator

Fondazione IRCCS Istituto Neurologico Carlo Besta

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 Hydrocephalus and Normal Pressure Hydrocephalus, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta 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 2 inclusion and 4 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: finished, as of the sponsor's last update on 11 Feb 2026. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison between study and control group (time frame: 4 years). 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 NCT06857136, which also lists 267 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 11 Feb 2026.