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Completed

NCT Number: NCT04166149

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

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.

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Key information

Conditions

Transplant;Failure,Kidney Rejection Acute Pancreas Rejection Acute Renal Transplant; Failure, Pancreas

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Georgetown University, Washington D.C., District of Columbia, United States

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About this study

+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:

  • Clinical T cell as well as antibody mediated acute rejection
  • Sub-clinical T cell as well as antibody mediated acute rejection
  • Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection.

The secondary endpoints for the study are:

  • 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.
  • Renal allograft injury from BKV (Polyomaviridae polyomavirus) nephritis, CNI (calcineurin inhibitor) toxicity, acute pyelonephritis and recurrent disease confirmed by renal histology.
  • Pancreas allograft function derived from hemoglobin A1c, insulin requirement, and serum c-peptide per SOC
  • Pancreas allograft injury from pancreatitis (all causes, including gastrointestinal dysmotility or viral).
  • Correlate cfDNA levels with presence or absence of delayed graft function (DGF) and subsequent outcomes in a subset of enrolled patients.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult recipients (Age > 18 years )
  • All genders and all racial and ethnic groups
  • Pancreas transplant alone (PTA)
  • Simultaneous kidney-pancreas transplantation (SPK)
  • Pancreas-after-kidney (PAK) 6. Simultaneous pancreas and living donor kidney (SPLK)
  • Primary or re-transplants 8. Ability to come for follow-up and undergo biopsy (Performed in accordance to SOC) 9. Provided consent

Exclusion criteria

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

Treatment and study plan

dd-cfDNA Blood Test

Diagnostic Test

The cfDNA measurement isolated from the peripheral blood contains small amounts from the graft. The blood sample is collected in Cell-Free DNA BCT (blood collection) tubes. These are measured by their difference in SNP (single nucleotide polymorphisms) genotype to determine the ratio of donor to recipient through shotgun sequencing. Higher levels of dd-cfDNA in a patient experiencing rejection is measured as a higher percentage of the total cf-DNA.

Primary outcomes

  1. dd-cfDNA correlation to acute rejection

    Time frame: 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.

    • Clinical T cell as well as antibody mediated acute rejection.
    • Sub-clinical T cell as well as antibody mediated acute rejection.
    • Composite of clinical and sub-clinical T cell as well as antibody mediated acute rejection.

Secondary outcomes

  1. dd-cfDNA correlation to pancreas and kidney function

    Time frame: 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.

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

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Collaborators

  • Georgetown University
  • University of Wisconsin, Madison

Registry information

Official study title

Non-invasive Blood Test to Diagnose Acute Rejection After Pancreas and Kidney Transplantation: Pancreas and Renal Rejection Diagnosis Using Circulating Donor-derived Cell-free DNA in Peripheral Blood

Acronym: PancDX

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
Nov 18, 2019
Registry last updated
Nov 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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