Cerebrospinal Fluid Proteome in Hydrocephalus (PROLIPHYC)

PROLIPHYC is a collaborative prospective study that aims at discovering deep cerebrospinal fluid (CSF) proteome with a new clinically-compatible proteomics strategy, in a cohort of 100 patients suspected of neurodegenerative diseases and/or normal pressure hydrocephalus.

Study Overview

• Status: Completed
• Conditions: Normal Pressure Hydrocephalus
• Intervention / Treatment: Biological: patient CSF extraction with hydrocephalus; Biological: witness CSF extraction

Detailed Description

CSF proteome is the real time protein content that may reveal useful biomarkers for diagnosis and therapeutic decision-making. But the low protein concentration in CSF and the low volumes typically obtained after lumbar puncture precludes the conventional use of proteomic analysis. We miniaturized the method to be compatible with low-volume samples by combination of nanoLC-MS/MS analysis and combinatorial peptide ligand library technology to reduce the dynamic range of protein concentration in CSF and unmask previously undetected proteins. We demonstrated that this deep proteomic analysis allows profiling the CSF proteome with a reasonable depth, in short analytical times and good accuracy. We settled a clinically-compatible proteomics strategy targeting the deep CSF proteome discovery.

The PROLIPHYC study is a prospective study that aims at analysing CSF proteome with our new strategy in a cohort of patients suspected of normal pressure hydrocephalus and/or related neurodegenerative diseases. The PROLIPHYC project combines detailed clinical and neuropsychological evaluation, gait analysis, MRI brain imaging, lumbar CSF dynamics and deep proteome. We hypothesize in the PROLIPHYC study that a specific cluster of polypeptides can be associated with Alzheimer disease, vascular dementia and normal pressure hydrocephalus profiles. Validating this hypothesis might be a significant step towards a proteomic lexicon of aging brain, neurodegenerative diseases and dementia.

Neurosciences department and Alzheimer disease centre from the Toulouse University Hospital are both involved in this project. The deep proteomic study is performed in Toulouse by the Institute of Pharmacology and Structural Biology with the academic support of the Institute of Mathematics of Toulouse.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Gait problems, cognitive decline, urinary incontinence and enlarged ventricles on imaging

Exclusion Criteria:

• Psychiatric disorders
• Lumbar punction contraindication
• RMI contraindication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patient; patient CSF extraction with hydrocephalus	Biological: patient CSF extraction with hydrocephalus; CSF extraction
Other: witness; patient without hydrocephalus but with peridural catheter for anesthetic. Witness CSF extraction has realized on catheter.	Biological: witness CSF extraction; CSF extraction from patient not suffering from hydrocephalus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF proteome measure	CSF extraction (3 ml)	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation between CSF proteome and gait analysis	compare results from CSF proteome and gait analysis	72 hours
correlation between CSF proteome and MRI brain imaging	compare results from CSF proteome and brain imaging	72 hours

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Eric SCHMIDT, MD PhD, University Hospital, Toulouse

Publications and helpful links

General Publications

• Guillotin S, Vallet A, Lorthois S, Cestac P, Schmidt E, Delcourt N. Association Between Homocysteine, Frailty and Biomechanical Response of the CNS in NPH-Suspected Patients. J Gerontol A Biol Sci Med Sci. 2022 Jul 5;77(7):1335-1343. doi: 10.1093/gerona/glac074.
• Vallet A, Del Campo N, Hoogendijk EO, Lokossou A, Baledent O, Czosnyka Z, Balardy L, Payoux P, Swider P, Lorthois S, Schmidt E. Biomechanical response of the CNS is associated with frailty in NPH-suspected patients. J Neurol. 2020 May;267(5):1389-1400. doi: 10.1007/s00415-019-09689-z. Epub 2020 Jan 29.
• Guillotin S, Fulzele A, Vallet A, de Peredo AG, Mouton-Barbosa E, Cestac P, Andrieu S, Burlet-Schiltz O, Delcourt N, Schmidt E. Cerebrospinal fluid proteomic profile of frailty: Results from the PROLIPHYC cohort. Aging Cell. 2024 Jul;23(7):e14168. doi: 10.1111/acel.14168. Epub 2024 May 2.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (Estimated): December 20, 2013

Study Record Updates

• Last Update Posted (Estimated): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: proteomic; cerebrospinal fluid; hydrocephalus
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus; Hydrocephalus, Normal Pressure
• Other Study ID Numbers: 10 045 08; 2011-A01091-40 (Other Identifier: AFSSAPS ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED