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

NCT04166149 | Completed DMC FDA Device

• 1 other identifier: Panc-DX
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• dd-cfDNA correlation to acute rejection

  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.

  August 1, 2019 to July 31, 2022

Secondary Outcomes (1)

• dd-cfDNA correlation to pancreas and kidney function

  August 1, 2019 to July 31, 2022

Study Arms (3)

University of Maryland

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.

Diagnostic Test: dd-cfDNA Blood Test

University of Wisconsin

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.

Diagnostic Test: dd-cfDNA Blood Test

Georgetown University

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.

Diagnostic Test: dd-cfDNA Blood Test

Interventions

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.

Georgetown University; University of Maryland; University of Wisconsin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• University of Wisconsin, Madison: collaborator
• Georgetown University: collaborator

Study Sites (3)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

UW Health University Hospital

Madison, Wisconsin, 53792, United States

Location

Related Publications (8)

• Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB 3rd, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M; Banff meeting report writing committee. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.

  PMID: 24472190 BACKGROUND

• Lo YM. Transplantation monitoring by plasma DNA sequencing. Clin Chem. 2011 Jul;57(7):941-2. doi: 10.1373/clinchem.2011.166686. No abstract available.

  PMID: 21566070 BACKGROUND

• Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28.

  PMID: 21444804 BACKGROUND

• Code of Federal Regulations, Title 42 - Public Health, Part 493 - Laboratory Requirements, Subpart A - General Provisions, Sections 1, 2 & 3.

  BACKGROUND

• Streck, Cell-Free DNA BCT Instructions for Use: EXT-REF-Q-00002

  BACKGROUND

• Hidestrand M, Tomita-Mitchell A, Hidestrand PM, Oliphant A, Goetsch M, Stamm K, Liang HL, Castleberry C, Benson DW, Stendahl G, Simpson PM, Berger S, Tweddell JS, Zangwill S, Mitchell ME. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. J Am Coll Cardiol. 2014 Apr 1;63(12):1224-1226. doi: 10.1016/j.jacc.2013.09.029. Epub 2013 Oct 16. No abstract available.

  PMID: 24140666 BACKGROUND

• 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.

  PMID: 23756769 BACKGROUND

• 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.

  PMID: 24944192 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples from recipients are taken in order to determine if peripheral blood has presence of donor-derived DNA.

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 18, 2019
• Study Start: September 1, 2019
• Primary Completion: July 30, 2024
• Study Completion: September 6, 2024
• Last Updated: November 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 2-3 years from study start.

Locations

US (3)