ABO Blood Group Antibody Elimination by a Combination of Semiselective Immunoadsorption Therapy and Membrane Filtration

January 15, 2018 updated by: Farsad Eskandary, Medical University of Vienna
  • Recipient desensitization protocols were shown to enable successful living donor kidney transplantation across major ABO blood group barriers. For extracorporeal depletion of circulating ABO antibodies plasmapheresis or ABO blood group specific immunoadsorption (IA) are most commonly used.
  • The efficiency of semiselective non-antigen specific IA in ABO-incompatible transplantation is currently not well established. One potential drawback of semiselective adsorbers could be an incomplete elimination of IgM.
  • This randomized controlled crossover trial was designed to clarify whether membrane filtration, as an adjunct to semiselective IA, can substantially enhance elimination of IgM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

-Background and study aims

ABO-incompatible living donor kidney transplantation offers the possibility to expand the donor pool by approximately 30%. A variety of different desensitization protocols were shown to enable successful transplantation across major ABO barriers. In this context, apheresis for antibody depletion represents the therapeutic mainstay. Two distinct technical principles, plasmapheresis and ABO antigen-specific immunoadsorption, were shown to allow for excellent short- and intermediate-term outcomes. A particular technical advantage of immunoadsorption may be its high selectivity regarding antibody depletion, which precludes major losses of essential plasma constituents, including coagulation factors and albumin, even after treatment of large plasma volumes. Nevertheless, high treatment costs associated with the use of ABO-specific columns (that are not approved for reuse) may limit their widespread clinical application.

The efficiency of semi-selective immunoadsorption technologies regarding ABO antibody depletion and recipient desensitization is less well established. Theoretically, non-antigen-specific immunoglobulin depletion using protein A-, GAM peptide-, or anti-Ig antibody-based adsorbers, could bring about several advantages, such as lower treatment costs associated with the use of reusable twin columns, and the potential to simultaneously deplete antibodies also against HLA antigens. A critical drawback, however, may be an evident inefficiency regarding (ABO-specific) IgM depletion, and this could pose a considerable risk of rejection.

One strategy to overcome the drawback of incomplete IgM depletion could be the use of semiselective immunoadsorption combined with other antibody depletion technologies. In this context, one attractive option could be an enhancement of antibody elimination by connecting a membrane filter (cascade filter) to the immunoadsorption device. We propose to conduct an open randomized crossover study that is designed to see if membrane filtration when applied as an adjunct to semiselective immunoadsorption (GAM peptide adsorbers) is able to enhance anti-ABO IgM elimination to an extent comparable to ABO antigen-specific immunoadsorption. The results of this study, which will enrol 14 patients receiving IA treatment for clinical indications outside the transplantation field, are expected to provide a valuable basis for the use of combined apheresis approaches in the context of ABO-incompatible kidney transplantation.

-Who can participate?

We are planning to recruit 14 adult patients (>18 years, both genders eligible, healthy volunteers not accepted) that are subject to regular routine IA therapy at >1 weekly intervals for clinical indications that are not related to ABO-incompatible transplantation (antibody-mediated autoimmune disorders, such as systemic lupus erythematosus or myasthenia gravis).

-What does the study involve?

For membrane filtration, we will use a membrane filter with documented capacity to eliminate plasma IgM. The study will be conducted in a randomized crossover design (AB vs. BA design; stratified randomization). Treatment consists in IA plus membrane filtration (A) or IA as the sole treatment (B), respectively. The primary study endpoint is the percent reduction of ABO blood group specific IgM. The study is powered to detect a 30% increase in IgM elimination.

-What are the possible benefits and risks of participating?

We do not expect any direct benefits for the study subjects. This pilot study, however, may provide a valuable basis for a future trial evaluating the clinical impact of combined IA plus membrane filtration in ABO incompatible transplantation. Potential risks include: adverse reactions upon exposure to polysulfone (rash, pruritus, fever), reduction in fibrinogen levels and eventually a transient increase in the risk of bleeding.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medical University of Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18a
  • Blood group A, B or O
  • Regular IA treatment for a disease not related to transplantation
  • Use of semiselective IA with GAM peptide adsorbers
  • IA treatment interval ≥ 7 days

Exclusion Criteria:

  • Age ≤ 18a
  • Blood group AB (no isoagglutinins)
  • No signed consent
  • Pregnancy or breast feeding women (exclusion of pregnancy with pregnancy test)
  • Severe disease precluding immunoglobulin elimination by IA (e.g. severe infection)
  • Elevated risk of bleeding or coagulation disorders that make systemic anticoagulation with heparin impossible
  • Hypersensitivity to heparin or HIT
  • Hypersensitivity to polysulfone
  • Participation in other clinical study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Semiselective IA
Semiselective immunoadsorption (GAM peptide adsorber)
Device: Semiselective IA
Semiselective immunoadsorption (GAM peptide adsorber)
EXPERIMENTAL: Semiselective IA + membrane filtration
Semiselective immunoadsorption (GAM peptide adsorber) in combination with membrane filtration
Device: Semiselective IA
Semiselective immunoadsorption (GAM peptide adsorber)
Device: Membrane filtration
Membrane filtration (Polysulfone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent reduction in flow cytometric ABO blood group specific IgM serum levels upon a single apheresis treatment
Time Frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).

Secondary Outcome Measures

Outcome Measure
Time Frame
Percent reduction in flow cytometric ABO blood group specific IgG serum levels upon a single apheresis treatment
Time Frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).

Other Outcome Measures

Outcome Measure
Time Frame
Effect on titers of ABO blood group specific IgG (indirect Coombs test)
Time Frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Effect on titers of ABO blood group specific IgM (direct agglutination test)
Time Frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Effect on concentrations of total serum IgG
Time Frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Effect on concentrations of total serum IgM
Time Frame: Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).
Blood samples will be taken within one hour before (baseline) and within one hour after each apheresis treatment (average apheresis duration 6 hours).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Collaborators

Fresenius Medical Care Deutschland GmbH

Investigators

  • Principal Investigator: Georg Böhmig, MD, Department of Nephrology, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (ACTUAL)

February 1, 2013

Study Completion (ACTUAL)

February 1, 2013

Study Registration Dates

First Submitted

September 26, 2012

First Submitted That Met QC Criteria

September 29, 2012

First Posted (ESTIMATE)

October 3, 2012

Study Record Updates

Last Update Posted (ACTUAL)

January 17, 2018

Last Update Submitted That Met QC Criteria

January 15, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • EK 1540/2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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