Nanoparticle for DSA Removal

Donor-specific Anti-human Leukocyte Antigen Antibodies (DSA) Re-moval From Patient Blood Using Functionalized Nanoparticles - an ex Vivo Feasibility and Proof of Principle Study

Magnetic nanoparticles, coated with human leukocyte antigens (HLA) to capture anti-HLA antibodies with donor specificity (donor-specific antibodies, DSA), will be tested ex-vivo.

Study Overview

• Status: Recruiting
• Conditions: Kidney Failure; Presence of Donor Specific Antibodies

Detailed Description

This project aims at developing a new method using human leukocyte antigens (HLA)-coated magnetic nanoparticles to remove donor-specific antibodies (DSA) from the patients' blood ex vivo, while trying to keep the blood unaffected after exposure to the particles.

Nanoparticles will be engineered and tested ex vivo. While nanoparticles were successfully coated with macromolecules such as antibodies in the past, this is a new approach, which will be performed by the research group.

The goal of this project is to capture DSA in patient blood ex vivo and to remove them by magnetic separation. Efficacy and safety of this procedure will be assessed, especially the interaction of these novel particles with other blood components such as coagulation factors or effector cells, which could produce inflammatory mediators. According analyses are initiated and carried out.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Beatrice Beck Schimmer, Prof; Phone Number: +41442552696 +41442552696; Email: beatrice.beck@usz.ch
• Study Contact Backup: Name: Martin Schläpfer, PD; Phone Number: +41442552696 +41442554690; Email: martin.schlaepfer@usz.ch

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich, Division of Anaesthesiology
      • Contact: Martin Schläpfer, PD; Phone Number: +41442554690; Email: martin.schlaepfer@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients suffering from kidney failure with DSA.

Description

Inclusion Criteria:

• DSA in the blood as detected by Luminex®
• Adults (>18 years old)
• Informed written consent

Exclusion Criteria:

• Inability to follow the procedures of the study, due to language problems, psychological disorders, social conditions or dementia
• Pregnancy and/or breast feeding
• Unwillingness to participate in this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
DSA in patients with kidney failure; Patients on kidney transplantation waiting list with DSA detected by Luminex (and mean fluorescence intensity (MFI) > 1000) in their blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of DSA removed in a blood sample using HLA-coated magnetic nanoparticles	Quantification of DSA removal using HLA-coated magnetic nanoparticles in comparison with blood treated with control nanoparticles (without HLA coating).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood coagulation (rotational thromboelastometry ROTEM, plasma clotting time) before and after treatment with HLA-coated magnetic nanoparticles	Coagulation parameters as described will be evaluated in blood samples. The same analyses will be repeated after exposure to HLA-coated magnetic nanoparticles.	1 day
Inflammatory blood mediators (IL-6, MCP-1) before and after treatment with HLA-coated magnetic nanoparticles	Inflammatory parameters as described will be evaluated in blood samples. The same analyses will be repeated after exposure to HLA-coated magnetic nanoparticles.	1 day

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Beatrice Beck Schimmer, Prof, University of Zurich

Publications and helpful links

General Publications

• Wan SS, Ying TD, Wyburn K, Roberts DM, Wyld M, Chadban SJ. The Treatment of Antibody-Mediated Rejection in Kidney Transplantation: An Updated Systematic Review and Meta-Analysis. Transplantation. 2018 Apr;102(4):557-568. doi: 10.1097/TP.0000000000002049.
• Herrmann IK, Beck-Schimmer B, Schumacher CM, Gschwind S, Kaech A, Ziegler U, Clavien PA, Gunther D, Stark WJ, Graf R, Schlegel AA. In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios. Nanomedicine (Lond). 2016 Apr;11(7):783-96. doi: 10.2217/nnm.16.22. Epub 2016 Mar 16.
• Jacobson M, Roth Z'graggen B, Graber SM, Schumacher CM, Stark WJ, Dumrese C, Mateos JM, Aemisegger C, Ziegler U, Urner M, Herrmann IK, Beck-Schimmer B. Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation. Nanomedicine (Lond). 2015;10(24):3537-46. doi: 10.2217/nnm.15.172. Epub 2015 Oct 5.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Anticipated): February 28, 2026
• Study Completion (Anticipated): February 28, 2026

Study Registration Dates

• First Submitted: February 13, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Kidney transplantation; Donor specific antibodies; Coated nanoparticles
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 2020-00295

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No