Clinical trial NCT04277377: Nanoparticle for DSA Removal
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Kidney Failure
Presence of Donor Specific Antibodies
Keywords: Donor specific antibodies
Kidney transplantation
Coated nanoparticles
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2020-02-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients suffering from kidney failure with DSA.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of DSA removed in a blood sample using HLA-coated magnetic nanoparticles
timeFrame: 1 day
Secondary outcomes:
measure: Blood coagulation (rotational thromboelastometry ROTEM, plasma clotting time) before and after treatment with HLA-coated magnetic nanoparticles
timeFrame: 1 day
measure: Inflammatory blood mediators (IL-6, MCP-1) before and after treatment with HLA-coated magnetic nanoparticles
timeFrame: 1 day
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Division of Anaesthesiology
state: ZH
Study officials:
affiliation: University of Zurich
name: Beatrice Beck Schimmer, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.