Cerebrospinal Fluid Proteome in Hydrocephalus

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Cerebrospinal Fluid Proteome in Hydrocephalus

Conditions
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Normal Pressure Hydrocephalus

Intervention / Treatment
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* Biological: patient CSF extraction with hydrocephalus
* Biological: witness CSF extraction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gait problems, cognitive decline, urinary incontinence and enlarged ventricles on imaging Exclusion Criteria: Psychiatric disorders Lumbar punction contraindication RMI contraindication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hydrocephalus, proteomic, cerebrospinal fluid