Clinical trial NCT04166149: Eliminating the Need for Pancreas Biopsy Using Peripheral Blood Cell-free DNA
Official 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Transplant;Failure,Kidney
Transplant; Failure, Pancreas
Rejection Acute Renal
Rejection Acute Pancreas
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: University of Wisconsin, Madison
name: Georgetown University
First posted: 2019-11-18
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with PTA, PAK, and SPK transplants. The data will compared to data obtained from the kidney transplant populations already investigated by CareDx in the DART and KOAR studies will be used as controls.

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.

Eligibility criteria: 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)

7. 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

Primary outcomes:
measure: dd-cfDNA correlation to acute rejection
timeFrame: August 1, 2019 to July 31, 2022
Secondary outcomes:
measure: dd-cfDNA correlation to pancreas and kidney function
timeFrame: August 1, 2019 to July 31, 2022
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Madison
country: United States
facility: UW Health University Hospital
state: Wisconsin
Study officials:
References:
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citation: Code of Federal Regulations, Title 42 - Public Health, Part 493 - Laboratory Requirements, Subpart A - General Provisions, Sections 1, 2 & 3.
citation: Streck, Cell-Free DNA BCT Instructions for Use: EXT-REF-Q-00002
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citation: Sigdel TK, Vitalone MJ, Tran TQ, Dai H, Hsieh SC, Salvatierra O, Sarwal MM. A rapid noninvasive assay for the detection of renal transplant injury. Transplantation. 2013 Jul 15;96(1):97-101. doi: 10.1097/TP.0b013e318295ee5a.
citation: De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.