Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04166149
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : February 24, 2022
Sponsor:
Collaborators:
University of Wisconsin, Madison
Georgetown University
Information provided by (Responsible Party):
Jonathan Bromberg, 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.

Condition or disease Intervention/treatment
Transplant;Failure,Kidney Transplant; Failure, Pancreas Rejection Acute Renal Rejection Acute Pancreas Diagnostic Test: dd-cfDNA Blood Test

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : September 1, 2019
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022

Group/Cohort Intervention/treatment
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
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.

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
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
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
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 Outcome Measures :
  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.

    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 :
  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.

    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).


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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04166149


Contacts
Layout table for location contacts
Contact: Jonathan S Bromberg, MD 4103280008 Jbromberg@som.umaryland.edu
Contact: Amanda Bartosic, MBA 4107061376 ABartosic@som.umaryland.edu

Locations
Layout table for location information
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Naomi Kalume       naomi.kalume@medstar.net   
Principal Investigator: Matthew Cooper, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Mariela Pinedo    410-706-1375    mpinedo@som.umaryland.edu   
United States, Wisconsin
UW Health University Hospital Recruiting
Madison, Wisconsin, United States, 53792
Contact: Kaelin Grant    608-576-0788    SurgeryResearch@surgery.wisc.edu   
Principal Investigator: John Odorico         
Sponsors and Collaborators
University of Maryland, Baltimore
University of Wisconsin, Madison
Georgetown University
Publications:
Code of Federal Regulations, Title 42 - Public Health, Part 493 - Laboratory Requirements, Subpart A - General Provisions, Sections 1, 2 & 3.
Streck, Cell-Free DNA BCT Instructions for Use: EXT-REF-Q-00002

Layout table for additonal information
Responsible Party: Jonathan Bromberg, Principal Investigator, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT04166149    
Other Study ID Numbers: Panc-DX
First Posted: November 18, 2019    Key Record Dates
Last Update Posted: February 24, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: As described in complete protocol.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 2-3 years from study start.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Renal Insufficiency
Kidney Diseases
Urologic Diseases