Personalization of Immunosuppressive Treatment for Organ Transplant Recipients

Study Overview
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Brief Summary
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Long-term graft failure rates continue to be unacceptably high despite the development of immunosuppressive drugs, underscoring the unmet need for robust prognostic biomarkers of allograft injury and failure. While rates of acute rejection (AR) continue to decrease, it remains the strongest predictor of long-term allograft survival, and so having a better understanding of factors predicting AR may contribute to more individualized patient care. Selecting optimum immunosuppressive dosage is another factor in personalizing kidney care. This project will study two areas of individualized kidney care: 1) assessing rejection by surveillance testing utilizing AlloSure, 2) developing an algorithm to select optimum immunosuppressive medication dosage.

Official Title
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Surveillance Testing Utilizing AlloSure to Assess Rejection Following Transplantation and Personalization of Immunosuppressive Therapy

Conditions
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Kidney Injury, Kidney Failure, Kidney Failure, Chronic, Kidney Failure, Acute, Kidney Diseases, Kidney Transplant Rejection, Kidney Transplant Infection, Kidney Transplant; Complications, Kidney Disease, Chronic, Kidney Ischemia

Intervention / Treatment
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* Diagnostic Test: AlloSure
* Diagnostic Test: PAXGene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult 18-80 year old Kidney transplant recipients (de novo or re-transplant, from living or deceased donor) BMI over 30 Recipients with pre formed human leukocyte antigens (HLA) antibodies Recipients with donor specific antibodies Recipients who have undergone blood type incompatible transplantation (ABO incompatible) Recipients who have had prior kidney transplants. Exclusion Criteria: Multi-Visceral transplant (simultaneous kidney pancreas, liver kidney, heart kidney) Contraindication to renal biopsy Refusing biopsy Kidney transplant recipient that is a monozygotic twin to the donor When more than two genomes may be present in the recipient plasma (more than recipient + donor): pregnancy, multiple-organ transplants from different donors (kidney after heart, kidney after liver transplant etc.), recipients of allogeneic blood or bone marrow transplant who have received cells with a genome different from the recipient (e.g. non-monozygotic twin)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AlloSure Assay prediction of Anti-body Mediated Rejection<br>Determine whether AlloSure predicts the incidence of active, chronic Anti-body Mediated Rejection and cellular rejection in high risk patients | Diagnostic Test: AlloSure<br>* AlloSure blood-draw at Post-operation day one and four, as well as one month, 2 months, 3, 9, 12, 15,18 and 24 months operation.<br>Diagnostic Test: PAXGene<br>* 1 PAXgene tube will be collected with every biopsy performed and sent with the AlloSure test for the second 100 patients (patients 101-200). 21 gene markers will be sequenced by collecting 3 ml of blood.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AlloSure value change | Examine if AlloSure predicts the incidence of active, chronic Active antibody mediated rejection (cAMR) and cellular rejection in high risk patients. This will be assessed through observing the changes in AlloSure values one draw after another. | post-operation day 1 and four. Pos-operation months 1, 2, 3,4,5,6 | 
| PAXGene, | The test will be used to develop an algorithm to personalize immunosuppressive medication intake. | 1 PAXgene tube will be collected 3 months post operation | 
| PAXGene | The test will be used to develop an algorithm to personalize immunosuppressive medication intake. | 1 PAXgene tube will be collected one year post operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploring the association between Cytochrome P450 (CYP) expression and Donor-Derived Cell-Free DNA (dd-cfDNA) | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that AlloSure will correlate with increased CYP expression. | post-operation day 1 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation day 4 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation month 1 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation month 2 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation month 3 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation month 4 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation month 5 | 
| Exploring the association between CYP expression and dd-cfDNA | Determine whether there is an association between CYP expression and dd-cfDNA in high risk patients and minority African American patients. CYP expression will be assessed with each AlloSure draw. We hypothesize that Allosure will correlate with increased CYP expression. | post-operation month 6 |