Improvement of Humoral Immune Response With Hemodialysis on BK-F Membrane: Correlation to Soluble CD40 Clearing

Study Overview
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Brief Summary
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The aim of this study is to improve the humoral immune response efficiency of hemodialyzed patient by the use of PMMA membrane (BK-F) able to clear the soluble form of CD40 in a model of anti-HBV vaccination

Detailed Description
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Chronic renal failure is associated with humoral immune alterations characterized by a diminished vaccine response notably against hepatitis B virus (HBV). Defects in cellular contact between immunological cells have been hypothesized to explain this observation but the precise mechanism leading to this immunocompromised status is not clear. The soluble form of CD40 (sCD40) is dramatically increased in the serum of uremic patients, particularly in the hemodialyzed patients. This molecule acts like an inhibitor of the CD40/CD154 contact, which is pivotal in the establishment of a proper humoral immune response. It has been shown that the most elevated sCD40 levels are associated with a lack of response to HBV vaccination in the hemodialyzed patients. The majority of the hemodialysis membranes, including high flux polysulfone membranes are unable to clear sCD40 from the sera. However, we found that the high flux polymethylmetacrylate (PMMA) membrane (BK-F Toray Medical Company, Japan) allows for sCD40 clearing. The aim of this study is to assess the effect of dialysis on PMMA membrane on the improvement of humoral immune response through the efficiency of HBV vaccination in hemodialysed patients who were non responders to one ore more previous vaccination and its link to sCD40 clearing.

Official Title
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Multicentric Randomized Trial of the Impact of Hemodialysis With Polymethylmetacrylate Membrane on the Improvement of Humoral Immune Response in the Hemodialyzed Patients: Application to Hepatitis B Vaccination and Correlation to sCD40 Clearing

Conditions
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Chronic Renal Failure, Humoral Immune Alterations

Intervention / Treatment
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* Procedure: High flux polymethylmetacrylate membrane
* Procedure: Polysulfone membrane
* Biological: Hepatitis B serological control
* Biological: Seric sCD40 level


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 80 years, male or female Patient not immunized against hepatitis B despite complete well done anterior vaccination according to recommendations Hemodialyzed patients with hemodialysed sessions performed three times a week Patient able to give informed consent and affiliated to the medical insurance Exclusion Criteria: Pregnant woman Patient never vaccinated against HBV Previous known hepatitis B even without anti HBs antibody (anti HBc antibody or HBs antigenemia positive) Active neoplasia or plasma cell dyscrasia VIH infection Known allergy to vaccine or to PMMA membrane Patient dialysed with PMMA membrane within three months before screening Necessity of acetate free biofiltration or hemodiafiltration as the technique of extrarenal epuration Vascular access problem with necessity of unipuncture for more than 30% of dialysis sessions. Patient under judicial protection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High flux polymethylmetacrylate membrane<br> | Procedure: High flux polymethylmetacrylate membrane<br>* Patients will be hemodialysed with high flux polymethylmetacrylate membranes<br>Biological: Hepatitis B serological control<br>* It will be assessed at week 16, week 20 and week 40<br>Biological: Seric sCD40 level<br>* Ir will be measured at inclusion and week 12 by ELISA test according to the manufacturer instructions.<br>|
| Active Comparator: Polysulfone membranes<br> | Procedure: Polysulfone membrane<br>* Patients be hemodialysed with polysulfone membranes<br>Biological: Hepatitis B serological control<br>* It will be assessed at week 16, week 20 and week 40<br>Biological: Seric sCD40 level<br>* Ir will be measured at inclusion and week 12 by ELISA test according to the manufacturer instructions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who will respond to vaccination |  | Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage and the level of anti-HBs antibodies |  | at week 16, week 20, week 24 and week 40 | 
| Correlation between the sCD40 levels and the response to HBV vaccination |  | At week 12 and week 40 | 
| Correlation between albuminemia, C-Reactive Protein, lymphocytes, parathyroid hormone, chronic immunosuppressive treatment or corticoid taking and vaccinal response. |  | at week 12, week 24, and week 36 |