Characterization of Removal Capacities of the Theranova Membrane by Proteomic Investigations

NCT ID: NCT03137056

Last Updated: 2017-05-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-31
• Study Completion Date: 2018-04-30

Brief Summary

Hemodialysis is the major technique of renal suppleance and membrane improvements allow an efficient depuration. During the past fifty years, improving the architecture of the membranes increased constantly the clearance of uremic toxins. Online-hemodiafiltration allowed a potential interest for decreasing morbi-mortality, but this technique is not available in all hemodialysis centers yet. Theranova membrane, by its innovating architecture, could be a valuable option for the enhancement of toxin removal in patients who are not eligible for online-hemodiafiltration techniques. Interestingly, many works pointed adsorptive capacities of dialysis membranes and these observations suggest that adsorption cannot be considered as an epiphenomenon. However, there is a lack of knowledge about the extent of its benefits in hemodialysis. The efficiency of a session of hemodialysis is routinely based on the clearance of only few generic toxins (urea, ß2-microglobulin, myoglobin). The eKT/V formula permitted to link a good depuration of urea with a better survival. EuTox described in a recent review, a large panel of middle molecules considered as uremic toxins. As there are many involved toxins, modern evaluation of hemodialysis efficiency can't be still based on the only description of ß2-microglobulin and urea removals. Inflammation status is routinely measured with blood levels of CRP. However, its accumulation is not leading to a toxicity. Many others inflammatory markers have been linked with morbidity and atherosclerosis, the main cause of mortality in ESRD patients. Obviously, removal of inflammatory markers by different dialyzers needs to be assess concomitantly but single conventional dosages are time-consuming.

A minimal albumin loss is considered as another important factor for a safe hemodialysis. Due to its multiple biological functions, albumin may be one of the most important protein for the maintenance of body homeostasis. Recent works were interested in the potential toxicity of some isoforms of the albumin and especially in chronic kidney disease. Modified forms of albumin have been linked with toxic properties and the removal of modified forms could be beneficial. Furthermore, albumin oxidation can lead to an under-estimation of albumin levels with the routinely used assay. A modern evaluation of the capacities of depuration of dialyzers clearly needs to integrate the evaluation of the clearance and generation of modified forms of albumin and proteins.

Proteomic techniques allow an interesting non-selective integrative approach. This exhaustive view would be particularly adequate for building a snapshot of blood uremic toxins, permeative and adsorptive capacities of each membrane. Due to a high sensitiveness, proteomic techniques can improve dramatically the characterization of the depuration capacities of different hemodialysis membranes considering a large range of uremic toxins especially with middle molecular weight, a large panel of inflammatory markers and modified forms of albumin. Furthermore, proteomic approach can help to build a quasi-exhaustive description of all the proteins removed by a membrane.

This project aims to compare the removal capacities of each membrane on a large range of proteins and forms of albumin (native and modified) with a highly-sensitive LC-MS/MS proteomic approach. We will also build the complete proteome of depuration of each tested membrane.

Conditions

Dialysis Membrane Reaction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Hemodialysis with Theranova

This arm is represented by the period during which the patients will undergo dialysis with the Theranova membrane.

Group Type: ACTIVE_COMPARATOR

Hemodialysis with Theranova

Intervention Type: DEVICE

Theranova is a polyarylethersulfone-based hemodialysis membrane manufactured by Baxter International Corp All the dialysis sessions in this arm will be performed with the theranova membrane. This membrane will exclusively be used in hemodialysis.

Modalities of hemodialysis : Blood flow: 300-400 mL/min; Dialysate flow: 500-800 mL/min

Hemodialysis with FX1000

This arm is represented by the period during which the patients will undergo dialysis with the FX1000 membrane.

Group Type: ACTIVE_COMPARATOR

Hemodialysis with FX1000

Intervention Type: DEVICE

FX1000 is a helixone-based membrane manufactured by Fresenius All the dialysis sessions in this arm will be performed with the FX1000 membrane. This membrane will be used in hemodialysis.

Modalities of hemodialysis: Blood flow: 300-400 mL/min ; Dialysate flow: 500-800 mL/min

Hemodiafiltration with FX1000

This arm is represented by the period during which the patients will undergo dialysis with the FX1000 membrane.

Group Type: ACTIVE_COMPARATOR

Hemodiafiltration with FX1000

Intervention Type: DEVICE

FX1000 is a helixone-based membrane manufactured by Fresenius All the dialysis sessions in this arm will be performed with the FX1000 membrane. This membrane will be used in hemodiafiltration Modalities of hemodialysis: Blood flow: 300-400 mL/min; Dialysate flow: 500-800 mL/min ; post reinjection convection volume of at least 25L.

Interventions

Hemodialysis with Theranova

Theranova is a polyarylethersulfone-based hemodialysis membrane manufactured by Baxter International Corp All the dialysis sessions in this arm will be performed with the theranova membrane. This membrane will exclusively be used in hemodialysis.

Modalities of hemodialysis : Blood flow: 300-400 mL/min; Dialysate flow: 500-800 mL/min

Intervention Type: DEVICE

Hemodialysis with FX1000

FX1000 is a helixone-based membrane manufactured by Fresenius All the dialysis sessions in this arm will be performed with the FX1000 membrane. This membrane will be used in hemodialysis.

Modalities of hemodialysis: Blood flow: 300-400 mL/min ; Dialysate flow: 500-800 mL/min

Intervention Type: DEVICE

Hemodiafiltration with FX1000

FX1000 is a helixone-based membrane manufactured by Fresenius All the dialysis sessions in this arm will be performed with the FX1000 membrane. This membrane will be used in hemodiafiltration Modalities of hemodialysis: Blood flow: 300-400 mL/min; Dialysate flow: 500-800 mL/min ; post reinjection convection volume of at least 25L.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old
• Patient on hemodialysis for at least 1 year
• Patient with a functional vascular access permitting at least 300 mL/min of blood flow.

Exclusion Criteria

• Running infection or other active disease (scheduled surgery, cancer, hospitalisation),
• Catheter as vascular access,
• Recirculation of vascular access over 10%.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Service de Néphrologie -Hypertension - Hémodialyse, Hôpital Edouard Herriot

Lyon, , France

Countries

France

Central Contacts

Caroline PELLETIER, MD

Role: CONTACT

caroline.pelettier02@chu-lyon.fr

472 11 01 59 ext. +33

Laurent JUILLARD, MD

Role: CONTACT

laurent.juillard@univ-lyon1.fr

472 11 01 59

Facility Contacts

Laurent JUILLARD, MD

Role: primary

Other Identifiers

69HCL17_0144

Identifier Type: -

Identifier Source: org_study_id