Nanoparticle for DSA Removal

Kidney Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04277377
• Other study ID #: 2020-00295
• Status: Recruiting
• Start date: October 5, 2021
• Est. completion date: February 28, 2026

Study information

• Verified date: March 2023
• Source: University of Zurich
• Contact: Beatrice Beck Schimmer, Prof
• Phone: +41442552696
• Email: beatrice.beck[@]usz.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 28, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Failure
• Presence of Donor Specific Antibodies
• Renal Insufficiency

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, Division of Anaesthesiology	Zurich	ZH

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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