Eliminating the Need for Pancreas Biopsy Using Peripheral Blood Cell-free DNA

Completed

• Conditions: Rejection Acute Renal; Transplant;Failure,Kidney; Rejection Acute Pancreas; Transplant; Failure, Pancreas
• Interventions: Diagnostic Test: dd-cfDNA Blood Test

• Registration Number: NCT04166149
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

Donor-derived cell-free DNA (dd-cfDNA) has shown promise as an early marker for cellular injury caused by rejection. dd-cfDNA changes may also indicate other injuries that lead to progressive decline in transplant organ function associated with, in the case of kidney transplantation, the presence of interstitial fibrosis (IF) and tubular atrophy (TA) seen in biopsy specimens. Here, we will study the utility of dd-cfDNA to predict rejection in pancreas and pancreas-kidney recipients.

Detailed Description

+Objective The objective of this prospective observational study is to correlate circulating dd-cfDNA to clinical and sub-clinical acute rejection in pancreas transplant alone (PTA), pancreas after kidney (PAK), and simultaneous pancreas kidney (SPK) allograft recipients. The secondary objective study is to correlate circulating dd-cfDNA to pancreas and kidney function, using Hgb1c, C-peptide and insulin requirement to assess pancreas function, and using serum creatinine and estimated glomerular filtration rate (eGFR) to assess kidney function.

The clinical data and specimen collection will also enable future biomarker research.

+Study endpoints Serial dd-cfDNA in individuals over time will be correlated with clinical status and outcomes, such as events of allograft dysfunction or biopsy proven rejection.

The primary endpoints of the study are:

1. Clinical T cell as well as antibody mediated acute rejection

2. Sub-clinical T cell as well as antibody mediated acute rejection

3. Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection.

The secondary endpoints for the study are:

1. eGFR (estimated Glomerular Filtration Rate \[mL/min\]): will be derived from serum creatinine level, corrected for variables, using the CKD-RPI (Chronic Kidney Disease Epidemiology Collaboration) equation.

2. Renal allograft injury from BKV (Polyomaviridae polyomavirus) nephritis, CNI (calcineurin inhibitor) toxicity, acute pyelonephritis and recurrent disease confirmed by renal histology.

3. Pancreas allograft function derived from hemoglobin A1c, insulin requirement, and serum c-peptide per SOC

4. Pancreas allograft injury from pancreatitis (all causes, including gastrointestinal dysmotility or viral).

5. Correlate cfDNA levels with presence or absence of delayed graft function (DGF) and subsequent outcomes in a subset of enrolled patients.

Study Timeline

• Study Start: 2019-09-01
• Study First Submitted: 2019-11-13
• Study First Submitted QC: 2019-11-13
• Study First Posted: 2019-11-18
• Primary Completion: 2024-07-30
• Study Completion: 2024-09-06
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1. Adult recipients (Age > 18 years )

2. All genders and all racial and ethnic groups

3. Pancreas transplant alone (PTA)

4. Simultaneous kidney-pancreas transplantation (SPK)

5. Pancreas-after-kidney (PAK) 6. Simultaneous pancreas and living donor kidney (SPLK)

6. Primary or re-transplants 8. Ability to come for follow-up and undergo biopsy (Performed in accordance to SOC) 9. Provided consent

Exclusion Criteria

1. Pediatric recipients (Age < 18 years)
2. Pregnant women
3. Patients undergoing multi-organ transplants not otherwise specified (e.g., pancreas-liver, multi-visceral, or pancreas-heart)
4. Patients receiving donor kidney from an identical twin, as part of an SPLK (see above)
5. Did not provide consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
University of Maryland	dd-cfDNA Blood Test	Pancreas and pancreas kidney patients enrolled at University of Maryland. Determine if dd-cfDNA exists in PTA, SPK, and PAK transplant recipient's blood by taking blood specimens at months 1-4, 6, 9, and 12 in the first year post transplant, and quarterly (month 15, 18, 21, 24) in the second year post transplant.
Georgetown University	dd-cfDNA Blood Test	Pancreas and pancreas kidney patients enrolled at Georgetown University. Determine if dd-cfDNA exists in PTA, SPK, and PAK transplant recipient's blood by taking blood specimens at months 1-4, 6, 9, and 12 in the first year post transplant, and quarterly (month 15, 18, 21, 24) in the second year post transplant.
University of Wisconsin	dd-cfDNA Blood Test	Pancreas and pancreas kidney patients enrolled at University of Wisconsin. Determine if dd-cfDNA exists in PTA, SPK, and PAK transplant recipient's blood by taking blood specimens at months 1-4, 6, 9, and 12 in the first year post transplant, and quarterly (month 15, 18, 21, 24) in the second year post transplant.

Primary Outcome Measures

Name	Time	Method
dd-cfDNA correlation to acute rejection	August 1, 2019 to July 31, 2022	To correlate circulating dd-cfDNA to clinical and sub-clinical acute rejection in PTA, PAK, and SPK allograft recipients.; 1. Clinical T cell as well as antibody mediated acute rejection.; 2. Sub-clinical T cell as well as antibody mediated acute rejection.; 3. Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection.

Secondary Outcome Measures

Name	Time	Method
dd-cfDNA correlation to pancreas and kidney function	August 1, 2019 to July 31, 2022	To correlate circulating dd-cfDNA to pancreas and kidney function, using Hgb1c, C-peptide and insulin requirement to assess pancreas function, and using serum creatinine and estimated glomerular filtration rate \[eGFR\] to assess kidney function.; 1. eGFR (estimated Glomerular Filtration Rate \[mL/min\]): will be derived from serum creatinine level, corrected for variables, using the CKD-RPI (Chronic Kidney Disease Epidemiology Collaboration) equation.; 2. Renal allograft injury from BKV (Polyomaviridae polyomavirus) nephritis, CNI (calcineurin inhibitor) toxicity, acute pyelonephritis and recurrent disease confirmed by renal histology.; 3. Pancreas allograft function derived from hemoglobin A1c, insulin requirement, and serum C-peptide per SOC 4. Pancreas allograft injury from pancreatitis (all causes, including gastrointestinal dysmotility or viral).

Trial Locations

Locations (3)

UW Health University Hospital; 🇺🇸 Madison, Wisconsin, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States