- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01545713
Correlation of Donor-specific Anti-endothelial Cells
A Phase II, Prospective, Single-center Study: Correlation of Donor-specific Anti-precursor Endothelial Cells With Transplant Outcome for Recipients of Living-donor Kidney Transplants, Are Auto-antibodies Important.
Antibody Mediated Rejection (AMR) is a major complication of solid organ transplantation. The main reason for AMR is pre-formed, or de-novo, donor specific antibodies against the donor human leukocyte antigens (HLA). Additional potential targets are antibodies against MIC-A antigens or antibodies against targets expressed on the donor endothelial cells.
Until recently, no specific means were available to test for the presence of donor-specific endothelial cell antibodies. The newly introduced XM-One AbSorber® assay allows isolating precursor endothelial cells from donor peripheral blood, and thus assessing the presence of donor-specific endothelial cell antibodies.
XM-One AbSorber® is an in-vitro assay that allows for the specific enrichment of precursor endothelial cells which in turn promotes endothelial cells specific cross match testing.
This assay is currently being used in an on-going Northwestern University (NU) research study (STU#00029988). The preliminary results of this study indicate that indeed some of the patients test positive against their respective donors. One potential explanation for this observation, that was not previously entertained, is that the antibodies causing the positive cross match response are actually of autoimmune nature. In order to rule-out such a potential explanation the investigators would like to further test these patients by performing an autologous XM-One AbSorber® assay in which the recipient sera will be incubated with the patients' own cells (as opposed to the respective donor cells in the parental study). This information is crucial for proper analysis of the data obtained in the NU STU#00029988 study.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Antibody Mediated Rejection (AMR) is a major complication of solid organ transplantation. The main reason for AMR is pre-formed, or de-novo, donor specific antibodies against the donor HLA antigens. Additional potential targets are antibodies against MIC-A antigens or antibodies against targets expressed on the donor endothelial cells.
Until recently, no specific means were available to test for the presence of donor-specific endothelial cell antibodies. The newly introduced XM-One AbSorber® assay allows isolating precursor endothelial cells from donor peripheral blood, and thus assessing the presence of donor-specific endothelial cell antibodies.
XM-One AbSorber® is an in-vitro assay that allows for the specific enrichment of precursor endothelial cells which in turn promotes endothelial cells specific cross match testing.
This assay is currently being used in an on-going Northwestern University (NU) research study (STU#00029988). The preliminary results of this study indicate that indeed some of the patients test positive against their respective donors. One potential explanation for this observation, that was not previously entertained, is that the antibodies causing the positive cross match response are actually of autoimmune nature. In order to rule-out such a potential explanation we would like to further test these patients by performing an autologous XM-One AbSorber® assay in which the recipient sera will be incubated with the patients' own cells (as opposed to the respective donor cells in the parental study). This information is crucial for proper analysis of the data obtained in the NU STU#00029988 study.
Initial data from our laboratory indicates that the antigens identified by the XM-One Absorber® assay differ from the HLA antigens usually identified by routine cross match assays. Moreover, we were able to document that this is a polymorphic system and therefore identifying a donor-specific source is critical.
Of the 150 patients already studied under NU research protocol STU#00029988 we found that 19 patients exhibited a positive response in a donor-specific XM-One AbSorber® assay. In this current research protocol study we want to follow-up on the specimens that exhibited a positive response in a donor-specific XM-One AbSorber® assay and perform an autologous XM-One AbSorber® assay to validate the clinical significance of our results.
There has been one multicenter study reported indicating the "XM-One AbSorber® is a quick, easy to perform on whole blood samples and identifies patients at risk for rejection and reduced graft function not identified by conventional lymphocyte cross matches" The primary objective is to complete additional testing for accuracy to determine whether antibodies directed at donor-specific endothelial cell effect transplant outcome.
The secondary objective is to assess the frequency of autologous antibodies that may be falsely reported as donor-specific anti-endothelial antibodies in our patient population. The single center research study we here at Northwestern University have been working on since May 19, 2010 thus far has resulted in 19 out of 150 specimens tested, have positive results based on the XM-One AbSorber® assay.
In this prospective study we plan to include all XM-One AbSorber® positive test results from all recipients of living-donor kidney transplants performed at Northwestern Memorial Hospital (NMH) since May 19, 2010 initial Institutional Review Board (IRB) approval until 250 transplants are performed. For this research protocol we will be targeting patients to consent only these individuals who have received a XM-One AbSorber® positive test result.
Each donor / recipient pair are required to send peripheral blood samples to the HLA laboratory prior to the scheduled transplant in order to perform lymphocyte cross match (to detect donor specific HLA antibodies; this is (SOC) standard of care). Left over serum and cells from these tests are being used to isolate an enriched precursor endothelial cell population and perform the XM-One AbSorber® assay (NU research protocol #STU00029988).
XM-One AbSorber® assay results - both autologous and allogeneic - will be captured and compared with graft outcome measurements at 3, 6, and 12 months post-transplant. Transplant outcome will be recorded as creatinine levels at the specific time points, protocol and for-cause biopsy results within the first year post transplant, diagnosis of acute cellular or humoral rejection, variation in immunosuppression levels, and any other complications.
Patients that exhibit a positive XM-One AbSorber® allogeneic cross match result will be requested to donate 4 green top tubes of peripheral blood. Cells obtained from this blood will be used in an autologous XM-One AbSorber® cross match assay using the original serum sample used for the allogeneic XM-One AbSorber® cross match assay.
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Illinois
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Chicago, Illinois, États-Unis, 60611
- Northwestern Memorial Hospital
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- patients older than 18 years of age
- patients undergoing living-donor kidney transplant at NMH who have a positive XM-One AbSorber® positive test result
Exclusion Criteria:
- patients undergoing deceased donor kidney transplant
- patients younger than 18 years of age
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Renal Transplant Recipients
Patients undergoing living-donor kidney transplant at NMH who have a positive XM-One AbSorber® positive test result.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
To complete additional testing for accuracy
Délai: June 2011 - February 2012
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The primary objective is to complete additional testing for accuracy to determine whether antibodies directed at donor-specific endothelial cell effect transplant outcome.
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June 2011 - February 2012
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
To assess the frequency of autologous antibodies.
Délai: June 2011 - February 2012
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To assess the frequency of autologous antibodies that may be falsely reported as donor-specific anti-endothelial antibodies in our patient population.
The single center research study we here at Northwestern University have been working on since May 19, 2010 thus far has resulted in 19 out of 150 specimens tested, have positive results based on the XM-One AbSorber® assay.
|
June 2011 - February 2012
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: John Friedewald, MD, Northwestern University
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Autres numéros d'identification d'étude
- XM-One AbSorber
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